WO2011151370A1 - N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues - Google Patents

N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues Download PDF

Info

Publication number
WO2011151370A1
WO2011151370A1 PCT/EP2011/059026 EP2011059026W WO2011151370A1 WO 2011151370 A1 WO2011151370 A1 WO 2011151370A1 EP 2011059026 W EP2011059026 W EP 2011059026W WO 2011151370 A1 WO2011151370 A1 WO 2011151370A1
Authority
WO
WIPO (PCT)
Prior art keywords
substituted
alkyl
different
halogen atoms
same
Prior art date
Application number
PCT/EP2011/059026
Other languages
French (fr)
Inventor
Jürgen BENTING
Pierre-Yves Coqueron
Pierre Cristau
Peter Dahmen
Philippe Desbordes
Stéphanie Gary
Jörg GREUL
Hiroyuki Hadano
Ruth Meissner
Ulrike Wachendorff-Neumann
Original Assignee
Bayer Cropscience Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Cropscience Ag filed Critical Bayer Cropscience Ag
Priority to AU2011260333A priority Critical patent/AU2011260333B2/en
Priority to CA2796194A priority patent/CA2796194A1/en
Priority to US13/700,716 priority patent/US8999956B2/en
Priority to KR1020127031072A priority patent/KR20130088022A/en
Priority to PL11723939T priority patent/PL2576517T3/en
Priority to BR112012030607-3A priority patent/BR112012030607B1/en
Priority to ES11723939.2T priority patent/ES2532971T3/en
Priority to EP11723939.2A priority patent/EP2576517B1/en
Priority to CN201180027220.8A priority patent/CN102918028B/en
Priority to MX2012013896A priority patent/MX2012013896A/en
Priority to UAA201214917A priority patent/UA107231C2/en
Priority to JP2013512887A priority patent/JP5730993B2/en
Publication of WO2011151370A1 publication Critical patent/WO2011151370A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/16—Halogen atoms or nitro radicals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage

Definitions

  • the present invention relates to fungicidal N-[(het)arylalkyl)] pyrazolecarboxamide or thiocarboxamide and their heterosubstituted analogues, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions.
  • fungicidal N-[(het)arylalkyl)] pyrazolecarboxamide or thiocarboxamide and their heterosubstituted analogues their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions.
  • certain fungicidal pyrazolecarboxamide derivatives are generically embraced in a broad disclosure of numerous compounds of the following formula :
  • A represents a substituted 5-membered heterocyclic group that can represent various rings among which a pyrazole ring
  • Z can represent a hydrogen atom, an alkyl group or a cycloalkyl group and the substituted or non-substituted 2-pyridyl group is linked to the pyrazolecarboxamide moeity by means of a 3- or 4-atoms linker.
  • A represents a 1-alkyl -3-(difluoro or dichloro)methyl-5-(chloro or fluoro)-4-pyrazolyl group.
  • A represents a substituted 5-membered heterocyclic group that can represent various rings among which a pyrazole ring
  • Z can represent a hydrogen atom, an alkyl group, an alkoxy group or a cycloalkyl group
  • Ar can represent a substituted or non-substituted phenyl or naphthyl group which is linked to the pyrazolecarboxamide moeity by means of a 3-, 4- or 5-atoms linker.
  • A represents a 1-alkyl-3-(difluoro or dichloro)methyl-5-(chloro or fluoro)-4-pyrazolyl group.
  • A represents a substituted 5-membered heterocyclic group that can represent various rings among which a pyrazole ring
  • Z can represent a hydrogen atom, an alkyl group or a cycloalkyl group
  • W can represent various substituted or non-substituted groups among which an alkyl group, a cycloalkylgroup, a trialkylsilyl group or a alkynyl group which are linked to the pyrazolecarboxamide moeity by means of a 2-, 3- or 4-atoms linker.
  • the present invention provides a N-[(het)arylalkyl)] pyrazolecarboxamide or thiocarboxamide derivative of formula (I)
  • X 1 and X 2 which can be the same or different, represent a halogen atom ;
  • Y represents a Ci-C 4 -alkyl
  • T represents O or S ;
  • B represents a phenyl ring that can be susbtituted by up to 5 groups X which can be the same or different ; a naphthyl ring that can be susbtituted by up to 7 groups X which can be the same or different ; a saturated, partially saturated or unsaturated, monocyclic or fused bicyclic 4-, 5-, 6-, 7- , 8-, 9-, 10-membered ring comprising from 1 up to 4 heteroaroms selected in the list consisting of N, O, S, that can be substituted by up to 6 groups X which can be the same or different ; a hydrogen atom ; a halogen atom ; a substituted or non-substituted Ci-Ci 2 -alkyl group ; a C 1 -C 12 - halogenoalkyl group having 1 to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C 3 -C 8 -
  • X represents a halogen atom ; nitro ; cyano ; isonitrile ; hydroxy ; amino ; sulfanyl ; pentafluoro- ⁇ 6 - sulfanyl ; formyl ; formyloxy ; formylamino ; substituted or non-substituted (hydroxyimino)-Ci-C 8 - alkyl ; substituted or non-substituted (Ci-C 8 -alkoxyimino)-Ci-C 8 -alkyl ; substituted or non- substituted (C 2 -C 8 -alkenyloxyimino)-Ci-C 8 -alkyl ; substituted or non-substituted (C 2 -C 8 - alkynyloxyimino)-Ci-C 8 -alkyl ; substituted or non-substituted (benzyloxyimino)-Ci-C 8 -al
  • ⁇ Z represents a hydrogen atom ; a formyl group ; a substituted or non-substituted Ci-C 8 -alkyl ; a substituted or non substituted Ci-C 8 -alkoxy ; a non-substituted C 3 -C 7 -cycloalkyl or a C 3 -C 7 - cycloalkyl substituted by up to 10 atoms or groups that can be the same or different and that can be selected in the list consisting of halogen atoms, cyano, Ci-C 8 -alkyl, Ci-C 8 -halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, Ci-C 8 -alkoxy, Ci-C 8 - halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, Ci-C 8 - alkoxycarbonyl, Ci-C 8 -halogenoalkoxycarbonyl comprising up
  • R and R 2 independently represent a hydrogen atom ; a halogen atom ; cyano ; substituted or non-substituted Ci-Ci 2 -alkyl ; substituted or non-substituted C 2 -Ci 2 -alkenyl ; substituted or non- substituted C 2 -Ci 2 -alkynyl ; substituted or non-substituted C 3 -C 7 -cycloalkyl ; Ci-Ci 2 -halogenoalkyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C 8 -alkoxy ; substituted or non- substituted Ci-C 8 -alkylsulfanyl ; substituted or non-substituted Ci-C 8 -alkylamino ; substituted or non-substituted di-(Ci-C 8 -alkyl)amino ; or substituted or non-substituted
  • Ci-C 2 -halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ;
  • Ci-C 8 -alkyl or Ci-C 2 -halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ;
  • R 3 and R 4 independently represent a hydrogen atom ; substituted or non-substituted Ci-C 8 -alkyl ; substituted or non-substituted C 2 -C 8 -alkenyl ; substituted or non-substituted C 2 -C 8 -alkynyl ; substituted or non-substituted C 3 -C 7 -cycloalkyl ; or Ci-C 8 -halogenoalkyl having 1 to 5 halogen atoms ; R 5 represents a hydrogen atom ; a substituted or non-substituted Ci-C 8 -alkyl ; a C-
  • R 6 and R 7 independently represent a substituted or non-substituted Ci-C 8 -alkyl ;
  • R a represents a hydrogen atom ; a substituted or non-substituted Ci-C 4 -alkyl ; or a Ci-C 4 - halogenoalkyl comprising up to 7 halogen atoms that can be the same or different ;
  • Q independently represents a halogen atom ; cyano ; nitro ; substituted or non-substituted Ci-C 8 - alkyl ; Ci-C 8 -halogenoalkyl having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C 8 -alkoxy ; Ci-C 8 -halogenoalkoxy having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C 8 -alkylsulfanyl ; Ci-C 8 - halogenoalkylsulfanyl having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted tri(Ci-C 8 )alkylsilyl ; substituted or non-substituted tri(Ci-C 8 )alkylsilyl-Ci-C 8 -alkyl ; substitute
  • Z does not represent a hydrogen atom when -Q -Q 2 - represents a unsubstituted cyclohexyl-1 ,2- diyl group and -Q 3 -Q 4 - represents a substituted or non-substituted cyclopropyl-1 ,2-diyl group ;
  • halogen means fluorine, bromine, chlorine or iodine
  • SO represents a sulfoxyde group
  • S0 2 represents a sulfone group
  • an alkyl group, an alkenyl group and an alkynyl group as well as moieties containing these terms, can be linear or branched;
  • the aryl moeity contained in an aryl group, an arylalkyl group, an arylalkenyl group and an arylalkynyl group as well as moieties containing these terms can be a phenyl group that can be substituted by up to 5 groups Q which can be the same or different, a naphthyl group that can be substituted by up to 7 groups Q which can be the same or different or a pyridyl group that can be substituted by up to 4 groups Q which can be the same or different ;
  • heteroatom means sulphur, nitrogen or oxygen.
  • a group or a substituent that is substituted according to the invention can be substituted by one or more of the following groups or atoms: a halogen atom, a nitro group, a hydroxy group, a cyano group, an amino group, a sulfanyl group, a pentafluoro- ⁇ 6 - sulfanyl group, a formyl group, a formyloxy group, a formylamino group, a carbamoyl group, a N- hydroxycarbamoyl group, a carbamate group, a (hydroxyimino)-Ci-C 6 -alkyl group, a Ci-C 8 -alkyl, a tri(Ci-C 8 -alkyl)silyl-Ci-C 8 -alkyl, Ci-C 8 -cycloalkyl, tri(Ci-C 8 -alkyl)silyl-Ci-C 8 -cycloalkyl,
  • any of the compounds of the present invention can exist in one or more optical or chiral isomer forms depending on the number of asymmetric centres in the compound.
  • the invention thus relates equally to all the optical isomers and to their racemic or scalemic mixtures (the term "scalemic” denotes a mixture of enantiomers in different proportions) and to the mixtures of all the possible stereoisomers, in all proportions.
  • the diastereoisomers and/or the optical isomers can be separated according to the methods which are known per se by the man ordinary skilled in the art.
  • any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the number of double bonds in the compound.
  • the invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions.
  • the geometric isomers can be separated according to general methods, which are known per se by the man ordinary skilled in the art.
  • Any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the relative position (syn/anti or cis/trans) of the substituents of ring B.
  • the invention thus relates equally to all syn/anti (or cis/trans) isomers and to all possible syn/anti (or cis/trans) mixtures, in all proportions.
  • the syn/anti (or cis/trans) isomers can be separated according to general methods, which are known per se by the man ordinary skilled in the art.
  • any of the compounds of formula (I) wherein X represents a hydroxy, a sulfanyl group or an amino group may be found in its tautomeric form resulting from the shift of the proton of said hydroxy, sulfanyl or amino group.
  • Such tautomeric forms of such compounds are also part of the present invention. More generally speaking, all tautomeric forms of compounds of formula (I) wherein X represents a hydroxy, a sulfanyl group or an amino group, as well as the tautomeric forms of the compounds which can optionally be used as intermediates in the preparation processes and which will be defined in the description of these processes, are also part of the present invention.
  • Preferred compounds according to the invention are compounds of formula (I) wherein X 1 and X 2 independently represent a chlorine or a fluorine atom. More preferred compounds according to the invention are compounds of formula (I) wherein X 1 and X 2 represent a fluorine atom ;
  • Other preferred compounds according to the invention are compounds of formula (I) wherein B represents a substituted or non-substituted phenyl ring ; a substituted or non-substituted naphthyl ring ; a substituted or non-substituted pyridyl ring ; a substituted or non-substituted thienyl ring ; or a substituted or non-substituted benzothienyl ring ; more preferred compounds according to the invention are compounds of formula (I) wherein B represents a substituted or non-substituted phenyl ring ; other more preferred compounds according to the invention are compounds of formula (I) wherein B represents a substituted or non-substituted 2-pyridyl ring ;
  • X independently represents a halogen atom ; substituted or non-substituted Ci-C 8 -alkyl ; C-
  • Even more preferred compounds according to the invention are compounds of formula (I) wherein X independently represents fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, terbutyl, cyclopropyl, cyclopentyl, cyclohexyl, trimethylsilyl, methoxy, ethoxy, methylsulfanyl, ethylsulfanyl, trifluoromethyl, trichloromethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethysulfanyl, trifluoromethylsulfanyl and difluorochloro- methylsulfanyl ;
  • Z represents a hydrogen atom ; a non-substituted C 3 -C 7 cycloalkyl ; or a C 3 -C 7 cycloalkyl substituted by up to 10 groups or atoms that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C 8 -alkyl, Ci-C 8 -halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, Ci-C 8 -alkoxy and Ci-C 8 -halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different ; more preferably Z represents a non-substituted C 3 -C 7 -cycloalkyl. ; even more preferably Z represents cyclopropyl ;
  • Other preferred compounds according to the invention are compounds of formula (I) wherein Q represents CR R 2 ;
  • Other preferred compounds according to the invention are compounds of formula (I) wherein Q 2 , Q 3 and Q 4 , which can be the same or different, represents a direct bond ; CR R 2 ; or O ;
  • More preferred compounds according to the invention are compounds of formula (I) wherein Q 2 represents CR R 2 and Q 3 and Q 4 represent a direct bond ;
  • R and R 2 independently represent a hydrogen atom, a fluorine atom, a substituted or non-substituted Ci-C 8 -alkyl or a substituted or non-substituted Ci-C 8 -alkoxy ;
  • R substituent of the group Q' and the R substituent of the group Q l+ together with the consecutive carbon atoms to which they are linked can form an optionally mono or polysubstituted 3-, 4-, 5-, 6- or 7-membered saturated carbocycle ; more preferably an optionally mono or polysubstituted cyclopropyl, cyclopentyl, cyclohexyl or a cycloheptyl ring ; even more preferably a cyclopropyl, a cyclopentyl or a cyclohexyl ring ;
  • R substituent of the group Q' and the R substituent of the group Q l+ together with the consecutive carbon atoms to which they are linked can form an cyclopentyl group that can be substituted by up to three groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
  • R substituent of the group Q' and the R substituent of the group Q l+ together with the consecutive carbon atoms to which they are linked can form an cyclohexyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
  • R substituent of the group Q' and the R substituent of the group Q l+ together with the consecutive carbon atoms to which they are linked can form an cycloheptyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
  • -Q -Q 2 - represents an optionally mono or polysubstituted cyclopentyl-1 ,2-diyl, cyclohexyl-1 ,2-diyl or cycloheptyl- 1 ,2-diyl group and -Q 3 -Q 4 -B represents a bicyclo[2.2.1]heptan-2-yl group, A 1 , A 2 , A 3 or A 4 wherein
  • R a represents hydrogen, Ci-C 4 -alkyl or Ci-C 4 -haloalkyl ;
  • Z represents -CR a2 R a3 R a4 or -Si R a2 R a3 R a4 ;
  • s 0, 1 , 2 or 3 ;
  • t 0 or 1 ;
  • R a2 , R a3 , R a4 independently of one another represent hydrogen, halogen Ci-C 4 -alkyl or Ci-C 4 - haloalkyl ;
  • R a3 and R a4 furthermore together with the carbon atom to which they are attached, can form an optionally substituted saturated or insaturated 3- to 6-membered carbocyclic ring ;
  • R a represents hydrogen or methyl ; s represents 0 or 1 ;
  • R a2 represents chlorine, methyl, ethyl, isopropyl or trifluoromethyl
  • R a3 represents chlorine, methyl, ethyl, isopropyl or trifluoromethyl
  • R a4 represents hydrogen, chlorine, methyl, ethyl, isopropyl or trifluoromethyl
  • a 2 represents , wherein
  • R a6 represent hydrogen, halogen, Ci-C 8 -alkyl or d-Cs-haloalkyl ;
  • R a5 , R a7 , R a8 independently of one another represent hydrogen, methyl or ethyl Particulary preferably,
  • R a5 represents hydrogen or methyl
  • R a6 represents hydrogen
  • R a7 represents hydrogen or methyl
  • R a8 represents fluorine, chlorine, methyl, ethyl or trifluoromethyl ;
  • R a represent hydrogen or fluorine
  • a 4 represents , wherein
  • R a ° represent optionally substituted C 2 -Ci 2 -alkyl, optionally substituted C 2 -C-i 2 -alkenyl, optionally substituted C 2 -Ci 2 -alkynyl, optionally substituted C 3 -C 8 -cycloalkyl, optionally substituted phenyl or heterocyclyl ;
  • R a 1 represent hydrogen or halogen ;
  • R a 2 represent hydrogen or halogen ;
  • R a ° represents ethyl, propyl, isopropyl, butyl, secbutyl, terbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, a-methylcyclopropyl, 4-fluorophenyl, 4-bromophenyl, 2-thienyl, 3-thienyl or 2-fury;
  • R a 1 represents hydrogen ;
  • R a 2 represents hydrogen
  • R 1 substituent of the group Q' and the R 1 substituent of the group Q l+2 together with the consecutive carbon atoms to which they are linked can form an optionally mono or polysusbtituted 4-, 5-, 6- or 7-membered saturated carbocycle ; more preferably an optionally mono or polysusbtituted cyclopentyl, cyclohexyl or a cycloheptyl ring ; even more preferably a cyclohexyl ring ;
  • R substituent of the group Q' and the R substituent of the group Q L+2 together with the consecutive carbon atoms to which they are linked can form an cyclohexyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
  • Even more prefered compounds according to the invention are compounds of formula (I) wherein -Q -Q 2 - Q 3 - represents an optionally mono or polysubstituted cyclohexyl-1 ,3-diyl and -Q 4 -B represents a bicyclo[2.2.1]heptan-2-yl group, or a A 1 , A 2 , A 3 or A 4 group as defined above.
  • Other preferred compounds according to the invention are compounds of formula (I) wherein R 3 and R 4 independently represent a hydrogen atom, or a substituted or non-substituted Ci-C 8 -alkyl;
  • R 5 represents a substituted or non-substituted Ci-C 8 -alkyl
  • R 6 and R 7 independently represent a non-substituted Ci-C 8 -alkyl ;
  • R 6 and R 7 independently represent a non-substituted Ci-C 3 -alkyl ;
  • R 6 and R 7 represent methyl
  • Y with preferred features of X 1 , X 2 , T, B, Z Q a 2 , a 3 , a 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and U;
  • T with preferred features of X 1 , X 2 , Y, B, Z Q a 2 , a 3 , a 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and U;
  • B with preferred features of X 1 , X 2 , Y, T, Z Q , Q 2 , Q 3 , Q 4 , R , R 2 , R 3 , R 4 , R 5 , R 6 ,
  • R - preferred features of R with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q 1 , Q 2 , Q 3 , Q 4 , R 2 , R 3 , R 4 , R 5 , R 6 ,
  • R 2 with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q ⁇ Q 2 , Q 3 , Q 4 , R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , X and U;
  • R 3 with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q 1 , Q 2 , Q 3 , Q 4 , R 1 , R 2 , R 4 , R 5 , R 6 ,
  • R 4 with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q 1 , Q 2 , Q 3 , Q 4 , R 1 , R 2 , R 3 , R 5 , R 6 ,
  • R 5 with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q 1 , Q 2 , Q 3 , Q 4 , R 1 , R 2 , R 3 , R 4 , R 6 ,
  • R 6 with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q 1 , Q 2 , Q 3 , Q 4 , R 1 , R 2 , R 3 , R 4 , R 5 ,
  • R 7 with preferred features of X 1 , X 2 , Y, T, B, Z 1 , Q 1 , Q 2 , Q 3 , Q 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and U;
  • the said preferred features can also be selected among the more preferred features of each of X 1 , X 2 , Y, T, B, Z Q a 2 , a 3 , a 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and U, so as to form most preferred subclasses of compounds according to the invention.
  • the present invention also relates to a process for the preparation of the compound of formula (I).
  • N-substituted amine derivatives of formula (II) are known or can be prepared by known processes such as reductive amination of aldehyde or ketone (Bioorganics and Medicinal Chemistry Letters (2006), 2014), or reduction of imines (Tetrahedron (2005), 1 1689), or nucleophilic substitution of halogen, mesylate or tosylate (Journal of Medicinal Chemistry (2002), 3887).
  • Carboxylic acid derivatives of formula (III) can be prepared according to process P2.
  • Suitable condensing agent may be selected in the non limited list consisting of acid halide former, such as phosgene, phosphorous tribromide, phosphorous trichloride, phosphorous pentachloride, phosphorous trichloride oxide or thionyl chloride; anhydride former, such as ethyl chloroformate, methyl chloroformate, isopropyl chloroformate, isobutyl chloroformate or methanesulfonyl chloride; carbodiimides, such as ⁇ , ⁇ '-dicyclohexylcarbodiimide (DCC) or other customary condensing agents, such as phosphorous pentoxide, polyphosphoric acid, N,N'-carbonyl- diimidazole, 2-ethoxy-N-ethoxycarbonyl-1 ,2-dihydroquinoline (DCC)
  • Suitable catalyst may be selected in the list consisting of 4-dimethyl-aminopyridine, 1-hydroxy-benzotriazole or dimethylformamide.
  • the process according to the present invention is conducted in the presence of an acid binder.
  • Suitable acid binders for carrying out process P1 according to the invention are in each case all inorganic and organic bases that are customary for such reactions.
  • alkaline earth metal alkali metal hydride, alkali metal hydroxides or alkali metal alkoxides, such as sodium hydroxide, sodium hydride, calcium hydroxide, potassium hydroxide, potassium tert- butoxide or other ammonium hydroxide
  • alkali metal carbonates such as cesium carbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, alkali metal or alkaline earth metal acetates, such as sodium acetate, potassium acetate, calcium acetateand also tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, pyridine, N-methylpiperidine, ⁇ , ⁇ -dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclo- nonene (DBN) or diazabicycloundecen
  • DABCO di
  • Step 1 of process P2 is performed in the presence of an oxidant, and if appropriate in the presence of a solvent.
  • Steps 2 and 5 of process P2 are performed in the presence of acid halide, and if appropriate in the presence of a solvent.
  • Step 3 of process P2 is performed in the presence of a fluorinating agent, and if appropriate in the presence of a solvent.
  • Step 4 of process P2 is performed in the presence of an acid or a base and if appropriate in the presence of a solvent
  • Suitable oxidants for carrying out step 1 of process P2 according to the invention are in each case all inorganic and organic oxidant which are customary for such reactions. Preference is given to using benzyltriethylammonium permanganate, bromine, chlorine, m-chloroperbenzoic acid, chromic acid, chromium (VI) oxide, hydrogen peroxide, hydrogen peroxide-boron trifluoride, hydrogen peroxide-urea, 2-hydroxyperoxyhexafluoro-2-propanol; Iodine, oxygen-platinum catalyst, perbenzoic acid, peroxyacetyl nitrate, potassium permanganate, potassium ruthenate, pyridinium dichromate, ruthenium (VIII) oxide, silver (I) oxide, silver (II) oxide, silver nitrite, sodium chlorite, sodium hypochlorite, or 2,2,6,6- tetramethylpiperidin-1-oxyl.
  • Suitable acid halides for carrying out steps 2 and 5 of process P2 according to the invention are in each case all organic or inorganic acid halides which are customary for such reactions. Preference is given to using notably phosgene, phosphorous trichloride, phosphorous pentachloride, phosphorous trichloride oxide, thionyl chloride, or carbon tetrachloride-triphenylphosphine.
  • Suitable fluorinating agent for carrying out step 3 of process P2 according to the invention is in each case all fluorinating agents which are customary for such reactions. Preference is given to using cesium fluoride, potassium fluoride, potassium fluoride-calcium difluoride, or tetrabutylammonium fluoride.
  • reaction temperatures can independently be varied within a relatively wide range.
  • processes according to the invention are carried out at temperatures between 0°C and 160°C, preferably between 10°C and 120°C.
  • a way to control the temperature for the processes according to the invention is to use the micro-waves technology.
  • Steps 1 to 5 of process P2 according to the invention are generally independently carried out under atmospheric pressure. However, in each case, it is also possible to operate under elevated or reduced pressure.
  • step 1 of process P2 When carrying out step 1 of process P2 according to the invention, generally one mole or other an excess of the oxidant is employed per mole of aldehyde of formula (IV). It is also possible to employ the reaction components in other ratios.
  • step 2 and 5 of process P2 to the invention generally one mole or other an excess of the acid halides is employed per mole of acid of formula (Ilia) or (Mid). It is also possible to employ the reaction components in other ratios.
  • X 1 , X 2 , Y, Z , Q , Q 2 , Q 3 , Q 4 and B are as herein-defined, in the optional presence of a catalytic or stoechiometric or more, quantity of a base such as an inorganic and organic base.
  • alkali metal carbonates such as sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate
  • heterocyclic aromatic bases such as pyridine, picoline, lutidine, collidine
  • tertiary amines such as trimethylamine, triethylamine, tributylamine, ⁇ , ⁇ -dimethylaniline, N,N-dimethyl- aminopyridine or N-methyl-piperidine.
  • Process P3 according to the invention is performed in the presence of a thionating agent.
  • Starting amide derivatives of formula (I) can be prepared according to processes P1.
  • Suitable thionating agents for carrying out process P3 according to the invention can be sulphur (S), sulfhydric acid (H 2 S), sodium sulfide (Na 2 S), sodium hydrosulfide (NaHS), boron trisulfide (B 2 S 3 ), bis(diethylaluminium) sulfide ((AIEt 2 ) 2 S), ammonium sulfide ((NH 4 ) 2 S), phosphorous pentasulfide (P 2 S 5 ), Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1 ,2,3,4-dithiadiphosphetane 2,4-disulfide) or a polymer- supported thionating reagent such as described in Journal of the Chemical Society, Perkin 1 (2001 ), 358.
  • S sulphur
  • H 2 S sulfhydric acid
  • Na 2 S sodium sulfide
  • the compound according to the present invention can be prepared according to the general processes of preparation described above. It will nevertheless be understood that, on the basis of his general knowledge and of available publications, the skilled worker will be able to adapt this method according to the specifics of each of the compounds, which it is desired to synthesize.
  • the present invention also relates to a fungicide composition
  • a fungicide composition comprising an effective and non-phytotoxic amount of an active compound of formula (I).
  • fungicide composition comprising, as an active ingredient, an effective amount of a compound of formula (I) as herein defined and an agriculturally acceptable support, carrier or filler.
  • the term "support” denotes a natural or synthetic, organic or inorganic compound with that the active compound of formula (I) is combined or associated to make it easier to apply, notably to the parts of the plant.
  • This support is thus generally inert and should be agriculturally acceptable.
  • the support can be a solid or a liquid.
  • suitable supports include clays, natural or synthetic silicates, silica, resins, waxes, solid fertilisers, water, alcohols, in particular butanol, organic solvents, mineral and plant oils and derivatives thereof. Mixtures of such supports can also be used.
  • composition according to the invention can also comprise additional components.
  • the composition can further comprise a surfactant.
  • the surfactant can be an emulsifier, a dispersing agent or a wetting agent of ionic or non-ionic type or a mixture of such surfactants.
  • the presence of at least one surfactant is generally essential when the active compound and/or the inert support are water-insoluble and when the vector agent for the application is water.
  • surfactant content can be comprised from 5% to 40% by weight of the composition.
  • composition according to the invention can contain from 0.05 to 99% by weight of active compound, preferably 10 to 70% by weight.
  • compositions according to the invention can be used in various forms such as aerosol dispenser, capsule suspension, cold fogging concentrate, dustable powder, emulsifiable concentrate, emulsion oil in water, emulsion water in oil, encapsulated granule, fine granule, flowable concentrate for seed treatment, gas (under pressure),gas generating product, granule, hot fogging concentrate, macrogranule, microgranule, oil dispersible powder, oil miscible flowable concentrate, oil miscible liquid, paste, plant rodlet, powder for dry seed treatment, seed coated with a pesticide, soluble concentrate, soluble powder, solution for seed treatment, suspension concentrate (flowable concentrate), ultra low volume (ULV) liquid, ultra low volume (ULV) suspension, water dispersible granules or tablets, water dispersible powder for slurry treatment, water soluble granules or tablets, water soluble powder for seed treatment and wettable powder.
  • These compositions include not only compositions that are ready to be applied to the plant or seed to
  • the compounds according to the invention can also be mixed with one or more insecticide, fungicide, bactericide, attractant, acaricide or pheromone active substance or other compounds with biological activity.
  • the mixtures thus obtained have normally a broadened spectrum of activity.
  • the mixtures with other fungicide compounds are particularly advantageous.
  • fungicide mixing partners can be selected in the following lists:
  • Inhibitors of the ergosterol biosynthesis for example (1.1 ) aldimorph (1704-28-5), (1 .2) azaconazole
  • inhibitors of the respiratory chain at complex I or II for example (2.1 ) bixafen (581809-46-3), (2.2) boscalid (188425-85-6), (2.3) carboxin (5234-68-4), (2.4) diflumetorim (130339-07-0), (2.5) fenfuram (24691-80-3), (2.6) fluopyram (658066-35-4), (2.7) flutolanil (66332-96-5), (2.8) fluxapyroxad (907204-31-
  • furametpyr (123572-88-3), (2.10) furmecyclox (60568-05-0), (2.1 1 ) isopyrazam (mixture of syn- epimeric racemate 1 RS,4SR,9RS and anti-epimeric racemate 1 RS,4SR,9SR) (881685-58-1 ), (2.12) isopyrazam (anti-epimeric racemate 1 RS,4SR,9SR), (2.13) isopyrazam (anti-epimeric enantiomer 1 R,4S,9S), (2.14) isopyrazam (anti-epimeric enantiomer 1 S,4R,9R), (2.15) isopyrazam (syn epimeric racemate 1 RS,4SR,9RS), (2.16) isopyrazam (syn-epimeric enantiomer 1 R,4S,9R), (2.17) isopyrazam (syn-epimeric enantiomer 1
  • inhibitors of the respiratory chain at complex III for example (3.1 ) ametoctradin (865318-97-4), (3.2) amisulbrom (348635-87-0), (3.3) azoxystrobin (131860-33-8), (3.4) cyazofamid (1201 16-88-3), (3.5) coumethoxystrobin (850881-30-0), (3.6) coumoxystrobin (850881-70-8), (3.7) dimoxystrobin (141600-52-
  • Inhibitors of the mitosis and cell division for example (4.1 ) benomyl (17804-35-2), (4.2) carbendazim (10605-21-7), (4.3) chlorfenazole (3574-96-7), (4.4) diethofencarb (87130-20-9), (4.5) ethaboxam (162650-77-3), (4.6) fluopicolide (2391 10-15-7), (4.7) fuberidazole (3878-19-1 ), (4.8) pencycuron (66063-
  • Inhibitors of the amino acid and/or protein biosynthesis for example (7.1 ) andoprim (23951-85-1 ), (7.2) blasticidin-S (2079-00-7), (7.3) cyprodinil (121552-61-2), (7.4) kasugamycin (6980-18-3), (7.5) kasugamycin hydrochloride hydrate (19408-46-9), (7.6) mepanipyrim (1 10235-47-7), (7.7) pyrimethanil (531 12-28-0) and (7.8) 3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinoline (861647-32-7) (WO2005070917).
  • Inhibitors of the ATP production for example (8.1 ) fentin acetate (900-95-8), (8.2) fentin chloride (639- 58-7), (8.3) fentin hydroxide (76-87-9) and (8.4) silthiofam (175217-20-6).
  • Inhibitors of the cell wall synthesis for example (9.1 ) benthiavalicarb (177406-68-7), (9.2)
  • dimethomorph (1 10488-70-5), (9.3) flumorph (21 1867-47-9), (9.4) iprovalicarb (140923-17-7), (9.5) mandipropamid (374726-62-2), (9.6) polyoxins (1 1 1 13-80-7), (9.7) polyoxorim (22976-86-9), (9.8) validamycin A (37248-47-8) and (9.9) valifenalate (283159-94-4; 283159-90-0).
  • Inhibitors of the lipid and membrane synthesis for example (10.1 ) biphenyl (92-52-4), (10.2) chloroneb (2675-77-6), (10.3) dicloran (99-30-9), (10.4) edifenphos (17109-49-8), (10.5) etridiazole (2593-15-9), (10.6) iodocarb (55406-53-6), (10.7) iprobenfos (26087-47-8), (10.8) isoprothiolane (50512- 35-1 ), (10.9) propamocarb (25606-41-1 ), (10.10) propamocarb hydrochloride (25606-41-1 ), (10.1 1 ) prothiocarb (19622-08-3), (10.12) pyrazophos (13457-18-6), (10.13) quintozene (82-68-8), (10.14) tecnazene (1 17-18-0) and (10.15) tolclofos-methyl (57018-04-9).
  • Inhibitors of the melanine biosynthesis for example (1 1.1 ) carpropamid (104030-54-8), (1 1.2) diclocymet (139920-32-4), (1 1.3) fenoxanil (1 15852-48-7), (1 1 .4) phthalide (27355-22-2), (1 1.5) pyroquilon (57369-32-1 ), (1 1 .6) tricyclazole (41814-78-2) and (1 1.7) 2,2,2-trifluoroethyl ⁇ 3-methyl-1-[(4- methylbenzoyl)amino]butan-2-yl ⁇ carbamate (851524-22-6) (WO2005042474).
  • Inhibitors of the nucleic acid synthesis for example (12.1 ) benalaxyl (71626-1 1-4), (12.2) benalaxyl- M (kiralaxyl) (98243-83-5), (12.3) bupirimate (41483-43-6), (12.4) clozylacon (67932-85-8), (12.5) dimethirimol (5221-53-4), (12.6) ethirimol (23947-60-6), (12.7) furalaxyl (57646-30-7), (12.8) hymexazol (10004-44-1 ), (12.9) metalaxyl (57837-19-1 ), (12.10) metalaxyl-M (mefenoxam) (70630-17-0), (12.1 1 ) ofurace (58810-48-3), (12.12) oxadixyl (77732-09-3) and (12.13) oxolinic acid (14698-29-4).
  • Inhibitors of the signal transduction for example (13.1 ) chlozolinate (84332-86-5), (13.2) fenpiclonil (74738-17-3), (13.3) fludioxonil (131341-86-1 ), (13.4) iprodione (36734-19-7), (13.5) procymidone (32809-16-8), (13.6) quinoxyfen (124495-18-7) and (13.7) vinclozolin (50471-44-8).
  • composition according to the invention comprising a mixture of a compound of formula (I) with a bactericide compound can also be particularly advantageous.
  • suitable bactericide mixing partners can be selected in the following list: bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracycline, probenazole, streptomycin, tecloftalam, copper sulphate and other copper preparations.
  • the compounds of formula (I) and the fungicide composition according to the invention can be used to curatively or preventively control the phytopathogenic fungi of plants or crops.
  • a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops characterised in that a compound of formula (I) or a fungicide composition according to the invention is applied to the seed, the plant or to the fruit of the plant or to the soil wherein the plant is growing or wherein it is desired to grow.
  • the method of treatment according to the invention can also be useful to treat propagation material such as tubers or rhizomes, but also seeds, seedlings or seedlings pricking out and plants or plants pricking out. This method of treatment can also be useful to treat roots.
  • the method of treatment according to the invention can also be useful to treat the overground parts of the plant such as trunks, stems or stalks, leaves, flowers and fruit of the concerned plant.
  • plants and plant parts can be treated.
  • plants are meant all plants and plant populations such as desirable and undesirable wild plants, cultivars and plant varieties (whether or not protectable by plant variety or plant breeder's rights).
  • Cultivars and plant varieties can be plants obtained by conventional propagation and breeding methods which can be assisted or supplemented by one or more biotechnological methods such as by use of double haploids, protoplast fusion, random and directed mutagenesis, molecular or genetic markers or by bioengineering and genetic engineering methods.
  • plant parts are meant all above ground and below ground parts and organs of plants such as shoot, leaf, blossom and root, whereby for example leaves, needles, stems, branches, blossoms, fruiting bodies, fruits and seed as well as roots, corms and rhizomes are listed.
  • Crops and vegetative and generative propagating material for example cuttings, corms, rhizomes, runners and seeds also belong to plant parts.
  • plants that can be protected by the method according to the invention mention may be made of major field crops like corn, soybean, cotton, Brassica oilseeds such as Brassica napus (e.g. canola), Brassica rapa, B. juncea (e.g. mustard) and Brassica carinata, rice, wheat, sugarbeet, sugarcane, oats, rye, barley, millet, triticale, flax, vine and various fruits and vegetables of various botanical taxa such as Rosaceae sp.
  • Brassica oilseeds such as Brassica napus (e.g. canola), Brassica rapa, B. juncea (e.g. mustard) and Brassica carinata, rice, wheat, sugarbeet, sugarcane, oats, rye, barley, millet, triticale, flax, vine and various fruits and vegetables of various botanical taxa such as Rosaceae sp.
  • Brassica oilseeds such as Brassica napus (e.g. canola
  • Anacardiaceae sp. Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp. (for instance banana trees and plantings), Rubiaceae sp. (for instance coffee), Theaceae sp., Sterculiceae sp., Rutaceae sp. (for instance lemons, oranges and grapefruit) ; Solanaceae sp. (for instance tomatoes, potatoes, peppers, eggplant), Liliaceae sp., Compositiae sp.
  • Umbelliferae sp. for instance carrot, parsley, celery and celeriac
  • Cucurbitaceae sp. for instance cucumber - including pickling cucumber, squash, watermelon, gourds and melons
  • Alliaceae sp. for instance onions and leek
  • Cruciferae sp. for instance white cabbage, red cabbage, broccoli, cauliflower, brussel sprouts, pak choi, kohlrabi, radish, horseradish, cress, Chinese cabbage), Leguminosae sp.
  • the method of treatment according to the invention can be used in the treatment of genetically modified organisms (GMOs), e.g. plants or seeds.
  • GMOs genetically modified organisms
  • Genetically modified plants are plants of which a heterologous gene has been stably integrated into genome.
  • the expression "heterologous gene” essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which are present in the plant (using for example, antisense technology, cosuppression technology or RNA interference - RNAi - technology).
  • a heterologous gene that is located in the genome is also called a transgene.
  • a transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
  • the treatment according to the invention may also result in superadditive (“synergistic") effects.
  • superadditive for example, reduced application rates and/or a widening of the activity spectrum and/or an increase in the activity of the active compounds and compositions which can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, bigger fruits, larger plant height, greener leaf color, earlier flowering, higher quality and/or a higher nutritional value of the harvested products, higher sugar concentration within the fruits, better storage stability and/or processability of the harvested products are possible, which exceed the effects which were actually to be expected.
  • the active compound combinations according to the invention may also have a strengthening effect in plants. Accordingly, they are also suitable for mobilizing the defense system of the plant against attack by unwanted microorganisms. This may, if appropriate, be one of the reasons of the enhanced activity of the combinations according to the invention, for example against fungi.
  • Plant- strengthening (resistance-inducing) substances are to be understood as meaning, in the present context, those substances or combinations of substances which are capable of stimulating the defense system of plants in such a way that, when subsequently inoculated with unwanted microorganisms, the treated plants display a substantial degree of resistance to these microorganisms.
  • unwanted microorganisms are to be understood as meaning phytopathogenic fungi, bacteria and viruses.
  • the substances according to the invention can be employed for protecting plants against attack by the abovementioned pathogens within a certain period of time after the treatment.
  • the period of time within which protection is effected generally extends from 1 to 10 days, preferably 1 to 7 days, after the treatment of the plants with the active compounds.
  • Plants and plant cultivars which are preferably to be treated according to the invention include all plants which have genetic material which impart particularly advantageous, useful traits to these plants (whether obtained by breeding and/or biotechnological means).
  • Plants and plant cultivars which are also preferably to be treated according to the invention are resistant against one or more biotic stresses, i.e. said plants show a better defense against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.
  • nematode resistant plants are described in e.g. US Patent Application Nos 1 1/765,491 , 1 1/765,494, 10/926,819, 10/782,020, 12/032,479, 10/783,417, 10/782,096, 1 1/657,964, 12/192,904, 1 1/396,808, 12/166,253, 12/166,239, 12/166,124, 12/166,209, 1 1/762,886, 12/364,335, 1 1/763,947, 12/252,453, 12/209,354, 12/491 ,396 or 12/497,221.
  • Plants and plant cultivars which may also be treated according to the invention are those plants which are resistant to one or more abiotic stresses.
  • Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients, shade avoidance.
  • Plants and plant cultivars which may also be treated according to the invention are those plants characterized by enhanced yield characteristics. Increased yield in said plants can be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation.
  • Yield can furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance.
  • Further yield traits include seed composition, such as carbohydrate content, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
  • Plants that may be treated according to the invention are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses). Such plants are typically made by crossing an inbred male-sterile parent line (the female parent) with another inbred male-fertile parent line (the male parent). Hybrid seed is typically harvested from the male sterile plants and sold to growers. Male sterile plants can sometimes (e.g. in corn) be produced by detasseling, i.e.
  • male sterility is the result of genetic determinants in the plant genome. In that case, and especially when seed is the desired product to be harvested from the hybrid plants it is typically useful to ensure that male fertility in the hybrid plants is fully restored. This can be accomplished by ensuring that the male parents have appropriate fertility restorer genes which are capable of restoring the male fertility in hybrid plants that contain the genetic determinants responsible for male-sterility. Genetic determinants for male sterility may be located in the cytoplasm.
  • CMS cytoplasmic male sterility
  • male sterile plants can also be obtained by plant biotechnology methods such as genetic engineering.
  • a particularly useful means of obtaining male-sterile plants is described in WO 89/10396 in which, for example, a ribonuclease such as barnase is selectively expressed in the tapetum cells in the stamens. Fertility can then be restored by expression in the tapetum cells of a ribonuclease inhibitor such as barstar (e.g. WO 91/02069).
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering
  • Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance.
  • Herbicide-resistant plants are for example glyphosate-tolerant plants, i.e. plants made tolerant to the herbicide glyphosate or salts thereof. Plants can be made tolerant to glyphosate through different means.
  • glyphosate-tolerant plants can be obtained by transforming the plant with a gene encoding the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS).
  • EPSPS 5-enolpyruvylshikimate-3-phosphate synthase
  • EPSPS 5-enolpyruvylshikimate-3-phosphate synthase
  • Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate oxido-reductase enzyme as described in U.S. Patent Nos. 5,776,760 and 5,463, 175. Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate acetyl transferase enzyme as described in for example WO 02/36782, WO 03/092360, WO 05/012515 and WO 07/024782. Glyphosate-tolerant plants can also be obtained by selecting plants containing naturally-occurring mutations of the above-mentioned genes, as described in for example WO 01/024615 or WO 03/013226. Plants expressing EPSPS genes that confer glyphosate tolerance are described in e.g. US Patent Application Nos 1 1/517,991 , 10/739,610, 12/139,408, 12/352,532,
  • herbicide resistant plants are for example plants that are made tolerant to herbicides inhibiting the enzyme glutamine synthase, such as bialaphos, phosphinothricin or glufosinate.
  • Such plants can be obtained by expressing an enzyme detoxifying the herbicide or a mutant glutamine synthase enzyme that is resistant to inhibition, e.g. described in US Patent Application No 1 1/760,602.
  • One such efficient detoxifying enzyme is an enzyme encoding a phosphinothricin acetyltransferase (such as the bar or pat protein from Streptomyces species).
  • Plants expressing an exogenous phosphinothricin acetyltransferase are for example described in U.S. Patent Nos. 5,561 ,236; 5,648,477; 5,646,024; 5,273,894; 5,637,489; 5,276,268; 5,739,082; 5,908,810 and 7, 1 12,665.
  • hydroxyphenylpyruvatedioxygenase HPPD
  • Hydroxyphenylpyruvatedioxygenases are enzymes that catalyze the reaction in which para-hydroxyphenylpyruvate (HPP) is transformed into homogentisate.
  • Plants tolerant to HPPD-inhibitors can be transformed with a gene encoding a naturally-occurring resistant HPPD enzyme, or a gene encoding a mutated or chimeric HPPD enzyme as described in WO 96/38567, WO 99/24585, WO 99/24586, WO 2009/144079, WO 2002/046387, or US 6,768,044..
  • Tolerance to HPPD-inhibitors can also be obtained by transforming plants with genes encoding certain enzymes enabling the formation of homogentisate despite the inhibition of the native HPPD enzyme by the HPPD-inhibitor. Such plants and genes are described in WO 99/34008 and WO 02/36787. Tolerance of plants to HPPD inhibitors can also be improved by transforming plants with a gene encoding an enzyme having prephenate deshydrogenase (PDH) activity in addition to a gene encoding an HPPD- tolerant enzyme, as described in WO 2004/024928.
  • PDH prephenate deshydrogenase
  • plants can be made more tolerant to HPPD- inhibitor herbicides by adding into their genome a gene encoding an enzyme capable of metabolizing or degrading HPPD inhibitors, such as the CYP450 enzymes shown in WO 2007/103567 and WO
  • Still further herbicide resistant plants are plants that are made tolerant to acetolactate synthase (ALS) inhibitors.
  • ALS-inhibitors include, for example, sulfonylurea, imidazolinone, triazolopyrimidines, pryimidinyoxy(thio)benzoates, and/or sulfonylaminocarbonyltriazolinone herbicides.
  • Different mutations in the ALS enzyme also known as acetohydroxyacid synthase, AHAS
  • AHAS acetohydroxyacid synthase
  • plants tolerant to imidazolinone and/or sulfonylurea can be obtained by induced mutagenesis, selection in cell cultures in the presence of the herbicide or mutation breeding as described for example for soybeans in U.S. Patent 5,084,082, for rice in WO 97/41218, for sugar beet in U.S. Patent 5,773,702 and WO 99/057965, for lettuce in U.S. Patent 5,198,599, or for sunflower in WO 01/065922.
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering
  • Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.
  • An "insect-resistant transgenic plant”, as used herein, includes any plant containing at least one transgene comprising a coding sequence encoding:
  • an insecticidal crystal protein from Bacillus thuringiensis or an insecticidal portion thereof such as the insecticidal crystal proteins listed by Crickmore et al. (1998, Microbiology and Molecular Biology Reviews, 62: 807-813), updated by Crickmore et al. (2005) at the Bacillus thuringiensis toxin nomenclature, online at:
  • insecticidal portions thereof e.g., proteins of the Cry protein classes CrylAb, CrylAc, Cryl B, Cryl C, Cryl D, Cryl F, Cry2Ab, Cry3Aa, or Cry3Bb or insecticidal portions thereof (e.g. EP 1999141 and WO 2007/107302), or such proteins encoded by synthetic genes as e.g. described in and US Patent Application No 12/249,016 ; or
  • a crystal protein from Bacillus thuringiensis or a portion thereof which is insecticidal in the presence of a second other crystal protein from Bacillus thuringiensis or a portion thereof, such as the binary toxin made up of the Cry34 and Cry35 crystal proteins (Moellenbeck et al. 2001 , Nat. Biotechnol. 19: 668-72; Schnepf et al. 2006, Applied Environm. Microbiol. 71 , 1765-1774) or the binary toxin made up of the CrylA or Cryl F proteins and the Cry2Aa or Cry2Ab or Cry2Ae proteins (US Patent Appl. No. 12/214,022 and EP 08010791.5); or
  • a hybrid insecticidal protein comprising parts of different insecticidal crystal proteins from Bacillus thuringiensis, such as a hybrid of the proteins of 1 ) above or a hybrid of the proteins of 2) above, e.g., the Cry1A.105 protein produced by corn event MON89034 (WO 2007/027777); or
  • VIP vegetative insecticidal
  • a secreted protein from Bacillus thuringiensis or Bacillus cereus which is insecticidal in the presence of a second secreted protein from Bacillus thuringiensis or B. cereus, such as the binary toxin made up of the VIPIA and VIP2A proteins (WO 94/21795); or
  • a hybrid insecticidal protein comprising parts from different secreted proteins from Bacillus thuringiensis or Bacillus cereus, such as a hybrid of the proteins in 1 ) above or a hybrid of the proteins in 2) above; or
  • an insect-resistant transgenic plant also includes any plant comprising a combination of genes encoding the proteins of any one of the above classes 1 to 10.
  • an insect-resistant plant contains more than one transgene encoding a protein of any one of the above classes 1 to 10, to expand the range of target insect species affected when using different proteins directed at different target insect species, or to delay insect resistance development to the plants by using different proteins insecticidal to the same target insect species but having a different mode of action, such as binding to different receptor binding sites in the insect.
  • an "insect-resistant transgenic plant”, as used herein, further includes any plant containing at least one transgene comprising a sequence producing upon expression a double-stranded RNA which upon ingestion by a plant insect pest inhibits the growth of this insect pest, as described e.g. in WO
  • 2007/080126 WO 2006/129204
  • WO 2007/074405 WO 2007/080127
  • WO 2007/035650 WO 2007/080126
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering which may also be treated according to the invention are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance. Particularly useful stress tolerance plants include:
  • plants which contain a transgene capable of reducing the expression and/or the activity of poly(ADP-ribose) polymerase (PARP) gene in the plant cells or plants as described in WO 00/04173, WO/2006/045633, EP 04077984.5, or EP 06009836.5.
  • PARP poly(ADP-ribose) polymerase
  • plants which contain a stress tolerance enhancing transgene coding for a plant-functional enzyme of the nicotineamide adenine dinucleotide salvage synthesis pathway including nicotinamidase, nicotinate phosphoribosyltransferase, nicotinic acid mononucleotide adenyl transferase, nicotinamide adenine dinucleotide synthetase or nicotine amide
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering which may also be treated according to the invention show altered quantity, quality and/or storage-stability of the harvested product and/or altered properties of specific ingredients of the harvested product such as :
  • transgenic plants which synthesize a modified starch, which in its physical-chemical characteristics, in particular the amylose content or the amylose/amylopectin ratio, the degree of branching, the average chain length, the side chain distribution, the viscosity behaviour, the gelling strength, the starch grain size and/or the starch grain morphology, is changed in comparison with the synthesised starch in wild type plant cells or plants, so that this is better suited for special applications.
  • Said transgenic plants synthesizing a modified starch are disclosed, for example, in EP 0571427, WO 95/04826, EP 0719338, WO 96/15248, WO
  • transgenic plants which synthesize non starch carbohydrate polymers or which synthesize non starch carbohydrate polymers with altered properties in comparison to wild type plants without genetic modification.
  • Examples are plants producing polyfructose, especially of the inulin and levan-type, as disclosed in EP 0663956, WO 96/01904, WO 96/21023, WO 98/39460, and WO 99/24593, plants producing alpha-1 ,4-glucans as disclosed in WO 95/31553, US 2002031826, US 6,284,479, US 5,712, 107, WO 97/47806, WO 97/47807, WO 97/47808 and WO 00/14249, plants producing alpha-1 ,6 branched alpha-1 ,4-glucans, as disclosed in WO 00/73422, plants producing alternan, as disclosed in e.g. WO 00/47727, WO 00/73422, EP 06077301.7, US 5,908,975
  • transgenic plants which produce hyaluronan, as for example disclosed in WO 2006/032538, WO 2007/039314, WO 2007/039315, WO 2007/039316, JP 2006304779, and WO 2005/012529.
  • transgenic plants or hybrid plants such as onions with characteristics such as 'high soluble solids content', 'low pungency' (LP) and/or 'long storage' (LS), as described in US Patent Appl. No. 12/020,360 and 61/054,026.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as cotton plants, with altered fiber characteristics.
  • plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered fiber characteristics and include:
  • Plants such as cotton plants, having fibers with altered reactivity, e.g. through the expression of N-acetylglucosaminetransferase gene including nodC and chitin synthase genes as described in WO 2006/136351
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered oil profile
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered seed shattering characteristics.
  • Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered seed shattering characteristics and include plants such as oilseed rape plants with delayed or reduced seed shattering as described in US Patent Appl. No. 61/135,230 WO09/068313 and WO10/006732.
  • transgenic plants which may be treated according to the invention are plants containing transformation events, or combination of transformation events, that are the subject of petitions for non- regulated status, in the United States of America, to the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA) whether such petitions are granted or are still pending.
  • APHIS Animal and Plant Health Inspection Service
  • USA United States Department of Agriculture
  • Petition the identification number of the petition.
  • Technical descriptions of the transformation events can be found in the individual petition documents which are obtainable from APHIS, for example on the APHIS website, by reference to this petition number. These descriptions are herein incorporated by reference.
  • Extension of Petition reference to a previous petition for which an extension is requested.
  • Institution the name of the entity submitting the petition.
  • Transgenic phenotype the trait conferred to the plants by the transformation event.
  • Transformation event or line the name of the event or events (sometimes also designated as lines or lines) for which nonregulated status is requested.
  • APHIS documents various documents published by APHIS in relation to the Petition and which can be requested with APHIS.
  • transgenic plants include plants containing a transgene in an agronomically neutral or beneficial position as described in any of the patent publications listed in Table C.
  • Botrytis resistance WO 2006/046861 WO 2002/085105
  • CMV-cucumber mosaic virus CPB-colorado potato beetle; PLRV- potato leafroll virus; PRSV-papaya ringspot virus; PVY-potato virus Y; WMV2- watermelon mosaic virus 2 ZYMV-zucchini yellow mosaic virus
  • Powdery mildew diseases such as :
  • Blumeria diseases caused for example by Blumeria graminis ;
  • Podosphaera diseases caused for example by Podosphaera leucotricha ;
  • Sphaerotheca diseases caused for example by Sphaerotheca fuliginea ;
  • Uncinula diseases caused for example by Uncinula necator ; Rust diseases such as :
  • Gymnosporangium diseases caused for example by Gymnosporangium sabinae ;
  • Hemileia diseases caused for example by Hemileia vastatrix ;
  • Phakopsora diseases caused for example by Phakopsora pachyrhizi or Phakopsora meibomiae ;
  • Puccinia diseases caused for example by Puccinia recondite, Puccinia graminis or
  • Uromyces diseases caused for example by Uromyces appendiculatus ;
  • Oomycete diseases such as :
  • Albugo diseases caused for example by Albugo Candida
  • Bremia diseases caused for example by Bremia lactucae ;
  • Peronospora diseases caused for example by Peronospora pisi or P. brassicae ;
  • Phytophthora diseases caused for example by Phytophthora infestans ;
  • Plasmopara diseases caused for example by Plasmopara viticola ;
  • Pseudoperonospora diseases caused for example by Pseudoperonospora humuli or
  • Pythium diseases caused for example by Pythium ultimum ;
  • Leafspot, leaf blotch and leaf blight diseases such as :
  • Alternaria diseases caused for example by Alternaria solani ;
  • Cercospora diseases caused for example by Cercospora beticola ;
  • Cladiosporum diseases caused for example by Cladiosporium cucumerinum ;
  • Cochliobolus diseases caused for example by Cochliobolus sativus (Conidiaform: Drechslera, Syn: Helminthosporium) or Cochliobolus miyabeanus ;
  • Colletotrichum diseases caused for example by Colletotrichum lindemuthanium ;
  • Cycloconium diseases caused for example by Cycloconium oleaginum ;
  • Diaporthe diseases caused for example by Diaporthe citri ;
  • Elsinoe diseases caused for example by Elsinoe fawcettii ;
  • Gloeosporium diseases caused for example by Gloeosporium laeticolor ;
  • Glomerella diseases caused for example by Glomerella cingulata ;
  • Guignardia diseases caused for example by Guignardia bidwelli ;
  • Leptosphaeria diseases caused for example by Leptosphaeria maculans ; Leptosphaeria nodorum ;
  • Magnaporthe diseases caused for example by Magnaporthe grisea ;
  • Mycosphaerella diseases caused for example by Mycosphaerella graminicola ; Mycosphaerella arachidicola ; Mycosphaerella fijiensis ;
  • Phaeosphaeria diseases caused for example by Phaeosphaeria nodorum ;
  • Pyrenophora diseases caused for example by Pyrenophora teres, or Pyrenophora tritici repentis;
  • Ramularia diseases caused for example by Ramularia collo-cygni , or Ramularia areola;
  • Rhynchosporium diseases caused for example by Rhynchosporium secalis ;
  • Septoria diseases caused for example by Septoria apii or Septoria lycopercisi ;
  • Typhula diseases caused for example by Typhula incarnata ;
  • Venturia diseases caused for example by Venturia inaequalis ; Root, Sheath and stem diseases such as :
  • Corticium diseases caused for example by Corticium graminearum ;
  • Fusarium diseases caused for example by Fusarium oxysporum ;
  • Gaeumannomyces diseases caused for example by Gaeumannomyces graminis ;
  • Rhizoctonia diseases caused for example by Rhizoctonia solani ;
  • Sarocladium diseases caused for example by Sarocladium oryzae;
  • Sclerotium diseases caused for example by Sclerotium oryzae
  • Tapesia diseases caused for example by Tapesia acuformis ;
  • Thielaviopsis diseases caused for example by Thielaviopsis basicola ;
  • Ear and panicle diseases such as :
  • Alternaria diseases caused for example by Alternaria spp. ;
  • Aspergillus diseases caused for example by Aspergillus flavus ;
  • Cladosporium diseases caused for example by Cladosporium spp. ;
  • Claviceps diseases caused for example by Claviceps purpurea ;
  • Fusarium diseases caused for example by Fusarium culmorum ;
  • Gibberella diseases caused for example by Gibberella zeae ;
  • Monographella diseases caused for example by Monographella nivalis ;
  • Smut and bunt diseases such as :
  • Sphacelotheca diseases caused for example by Sphacelotheca reiliana ;
  • Tilletia diseases caused for example by Tilletia caries ;
  • Urocystis diseases caused for example by Urocystis occulta ;
  • Ustilago diseases caused for example by Ustilago nuda ;
  • Aspergillus diseases caused for example by Aspergillus flavus ;
  • Botrytis diseases caused for example by Botrytis cinerea ;
  • Penicillium diseases caused for example by Penicillium expansum ;
  • Rhizopus diseases caused by example by Rhizopus stolonifer
  • Sclerotinia diseases caused for example by Sclerotinia sclerotiorum ;
  • Verticilium diseases caused for example by Verticilium alboatrum ;
  • Seed and soilborne decay, mould, wilt, rot and dam ping-off diseases Seed and soilborne decay, mould, wilt, rot and dam ping-off diseases :
  • Aphanomyces diseases caused for example by Aphanomyces euteiches
  • Ascochyta diseases caused for example by Ascochyta lentis
  • Cladosporium diseases caused for example by Cladosporium herbarum
  • Cochliobolus diseases caused for example by Cochliobolus sativus
  • Colletotrichum diseases caused for example by Colletotrichum coccodes
  • Fusarium diseases caused for example by Fusarium culmorum
  • Gibberella diseases caused for example by Gibberella zeae
  • Macrophomina diseases caused for example by Macrophomina phaseolina
  • Monographella diseases caused for example by Monographella nivalis
  • Penicillium diseases caused for example by Penicillium expansum
  • Phoma diseases caused for example by Phoma lingam
  • Phomopsis diseases caused for example by Phomopsis sojae
  • Phytophthora diseases caused for example by Phytophthora cactorum
  • Pyrenophora diseases caused for example by Pyrenophora graminea
  • Pyricularia diseases caused for example by Pyricularia oryzae
  • Pythium diseases caused for example by Pythium ultimum
  • Rhizoctonia diseases caused for example by Rhizoctonia solani;
  • Rhizopus diseases caused for example by Rhizopus oryzae
  • Sclerotium diseases caused for example by Sclerotium rolfsii;
  • Septoria diseases caused for example by Septoria nodorum
  • Typhula diseases caused for example by Typhula incarnata
  • Verticillium diseases caused for example by Verticillium dahliae ;
  • Canker, broom and dieback diseases such as :
  • Nectria diseases caused for example by Nectria galligena ;
  • Blight diseases such as :
  • Monilinia diseases caused for example by Monilinia laxa ;
  • Leaf blister or leaf curl diseases such as :
  • Exobasidium diseases caused for example by Exobasidium vexans
  • Taphrina diseases caused for example by Taphrina deformans ;
  • Esca diseases caused for example by Phaemoniella clamydospora ;
  • Eutypa dyeback caused for example by Eutypa lata ;
  • Ganoderma diseases caused for example by Ganoderma boninense
  • Rigidoporus diseases caused for example by Rigidoporus lignosus
  • Botrytis diseases caused for example by Botrytis cinerea
  • Rhizoctonia diseases caused for example by Rhizoctonia solani;
  • Helminthosporium diseases caused for example by Helminthosporium solani;
  • Plasmodiophora diseases cause for example by Plamodiophora brassicae.
  • Xanthomonas species for example Xanthomonas campestris pv. oryzae;
  • Pseudomonas species for example Pseudomonas syringae pv. lachrymans;
  • Erwinia species for example Erwinia amylovora.
  • the composition according to the invention may also be used against fungal diseases liable to grow on or inside timber.
  • the term "timber" means all types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood.
  • the method for treating timber according to the invention mainly consists in contacting one or more compounds according to the invention or a composition according to the invention; this includes for example direct application, spraying, dipping, injection or any other suitable means.
  • the dose of active compound usually applied in the method of treatment according to the invention is generally and advantageously from 10 to 800 g/ha, preferably from 50 to 300 g/ha for applications in foliar treatment.
  • the dose of active substance applied is generally and advantageously from 2 to 200 g per 100 kg of seed, preferably from 3 to 150 g per 100 kg of seed in the case of seed treatment.
  • the compounds or mixtures according to the invention can also be used for the preparation of composition useful to curatively or preventively treat human or animal fungal diseases such as, for example, mycoses, dermatoses, trichophyton diseases and candidiases or diseases caused by Aspergillus spp., for example Aspergillus fumigatus.
  • fungal diseases such as, for example, mycoses, dermatoses, trichophyton diseases and candidiases or diseases caused by Aspergillus spp., for example Aspergillus fumigatus.
  • Table 1 illustrates in a non-limiting manner examples of compounds of formula (I) according to the invention
  • M+H (Apcl+) means the molecular ion peak plus 1 a.m.u. (atomic mass unit) as observed in mass spectroscopy via positive atmospheric pressure chemical ionisation.
  • logP values were determined in accordance with EEC Directive 79/831 Annex V.A8 by HPLC (High Performance Liquid Chromatography) on a reversed-phase column (C 18), using the method described below :
  • # denotes the point of attachement to the amide moiety
  • Table 2 provides the NMR data ( H ) of a selected number of compounds from table 1.
  • Intensity of sharp signals correlates with the height of the signals in a printed example of a NMR spectrum in cm and shows the real relations of signal intensities. From broad signals several peaks or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.
  • the H-NMR peak lists are similar to classical H-NMR prints and contain therefore usually all peaks, which are listed at classical NMR-interpretation. Additionally they can show like classical 1 H- NMR prints signals of solvents, stereoisomers of the target compounds, which are also object of the invention, and/or peaks of impurities.
  • peaks of solvents for example peaks of DMSO in DMSO-d6 and the peak of water are shown in our H-NMR peak lists and have usually on average a high intensity.
  • the peaks of stereoisomers of the target compounds and/or peaks of impurities have usually on average a lower intensity than the peaks of target compounds (for example with a purity >90%).
  • Such stereoisomers and/or impurities can be typical for the specific preparation process. Therefore their peaks can help to recognize the reproduction of our preparation process via "side-products-fingerprints".
  • Step 1 preparation of of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid (llla-1 )
  • 6.0 g (31 mmol) of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbaldehyde are added to 30 ml of toluene.
  • a solution of 2.4 g (62 mmol) of sodium hydroxide in 6ml of water is added to the reaction mixture, followed by 103 ml of a 30% solution of hydrogen peroxide in water, whilst keeping the temperature below 37°C.
  • reaction mixture is stirred at 50°C for 7 hours. Once the reaction mixture is back to room temperature, the two phases are separated and the organic phase is extracted with 100 ml of water. The combined aqueous phases are acidified to pH 2 with aqueous hydrochloric acid. The resulting white precipitate is filtered, washed twice with 20 ml of water, and dried to yield 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid as a white solid.
  • Step 2 preparation of of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride (lllb-1 ) 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid and 44.3 ml of thionyl chloride are refluxed for 5 hours. After cooling down, the reaction mixture is evaporated under vacuum to yield 3.5 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride as a yellow oil.
  • Step 3 preparation of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl fluoride (lllc-1 )
  • a dried solution of 4.0 g (70 mmol) of potassium fluoride in 21 ml of tetrahydrothiophene-1 1 -dioxide is added a solution of 5.0 g (22 mmol) of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride in 15 ml of toluene at 100°C.
  • the resulting reaction mixture is stirred at 190-200°C for 22 hours.
  • Step 4 preparation of of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxylic acid (llld-1 )
  • llld-1 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxylic acid
  • Step 5 preparation of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride (llle-1 ) 9.1 g of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxylic acid and 75.5 ml of thionyl chloride are refluxed for 1.5 hours. After cooling down, the reaction mixture is evaporated under vacuum to yield 10 g of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride as a yellow oil.
  • Step 6 preparation of N-cyclopropyl-N-[2-(2,6-dichlorophenoxy)ethyl]-3-(difluoromethyl)-5-fluoro-1- m ethyl- 1 H-pyrazole-4-carboxam ide
  • Step 1 preparation of methyl 1-(3,3-dimethylbutyl)-2-oxocyclopentanecarboxylate
  • Step 3 preparation of 2-(3,3-dimethylbutyl)-N-hydroxycyclopentanimine
  • Step 4 preparation of 2-(3,3-dimethylbutyl)cyclopentanamine hydrochloride (1 :1 )
  • Step 5 preparation of 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)cyclopentyl]-5-fluoro-1-methyl-1 H- pyrazole-4-carboxamide
  • Step 1 3-(3,3-dimethylbut-1-yn-1-yl)aniline
  • reaction solution is concentrated under reduced pressure and the residue formed is stirred into 1 I of water.
  • the mixture is then extracted three times with diethyl ether.
  • the combined organic phases are once more washed with water, dried with sodium sulphate and concentrated under reduced pressure.
  • the crude product obtained is purified by silica gel chromatography (mobile phase methylene chloride).
  • Step 3 preparation of 3-(difluoromethyl)-N-[3-(3,3-dimethylbutyl)cyclohexyl]-5-fluoro-1-methyl-1 H- py razo le-4-carboxa m id e
  • Example A in vivo preventive test on Sphaerotheca fuliginea (cucumber)
  • Emulsifier 1 part by weight of Alkylarylpolyglycolether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the test is evaluated 7 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • the des-fluoro analogue compound CMP1 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N- [(2-phenylcyclohexyl)methyl]-1 H-pyrazole-4-carboxamide.
  • the des-fluoro analogue compound CMP2 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-(3- phenylcyclohexyl)-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP3 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-(3-phenylcyclohexyl)-1 H-pyrazole-4- carboxamide.
  • the des-fluoro analogue compound CMP4 corresponds to N-[1 , 1 '-bi(cyclohexyl)-2-yl]-5-fluoro-1 ,3- dimethyl-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP5 corresponds to N- [1 , 1 '-bi(cyclohexyl)-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
  • Example B in vivo preventive test on Altemaria solani (tomato)
  • Emulsifier 1 part by weight of Alkylarylpolyglycolether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • Table B 127 90 194 70 319 100
  • Table B (next) :
  • the des-halogeno analogue compound CMP6 corresponds to 3-(difluoromethyl)-1-methyl-N-(1- phenoxypropan-2-yl)-1 H-pyrazole-4-carboxamide.
  • the des-fluoro analogue compound CMP7 corresponds to N-(2-tert-butylcyclohexyl)-3-(difluoromethyl)-1- m ethyl- 1 H-pyrazole-4-carboxam ide.
  • Example C in vivo preventive test on Pyrenophora teres (barley)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the test is evaluated 7-9 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control while an efficacy of 100 % means that no disease is observed.
  • the des-fluoro analogue compound CMP8 corresponds to N-(2-hexylcyclohexyl)-1-methyl-3- (trifluoromethyl)-1 H-pyrazole-4-carboxamide.
  • Example D in vivo preventive test on Venturia inaepualis (apple scab)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are then placed in a greenhouse at approximately 21 °C and a relative atmospheric humidity of approximately 90 %.
  • the test is evaluated 10 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Example E in vivo preventive test on Septoria tritici (wheat)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are sprayed with a spore suspension of Septoria tritici.
  • the plants remain for 48 hours in an incubation cabinet at approximately 20°C and a relative atmospheric humidity of approximately 100 % and afterwards for 60 hours at approximately 15°C in a translucent incubation cabinet at a relative atmospheric humidity of approximately 100 %.
  • the plants are placed in the greenhouse at a temperature of approximately 15°C and a relative atmospheric humidity of approximately 80 %.
  • the test is evaluated 21 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Example F in vivo preventive test on Blumeria graminis (barley)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are dusted with spores of Blumeria graminis f.sp. hordei.
  • the plants are placed in the greenhouse at a temperature of approximately 18°C and a relative atmospheric humidity of approximately 80 % to promote the development of mildew pustules.
  • the test is evaluated 7 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Example G in vivo preventive test on Fusarium nivale (wheat)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are slightly injured by using a sandblast and afterwards they are sprayed with a conidia suspension of Fusarium nivale (var. majus).
  • the plants are placed in the greenhouse under a translucent incubation cabinet at a temperature of approximately 10°C and a relative atmospheric humidity of approximately 100 %.
  • the test is evaluated 5 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are slightly injured by using a sandblast and afterwards they are sprayed with a conidia suspension of Fusarium graminearum.
  • the plants are placed in the greenhouse under a translucent incubation cabinet at a temperature of approximately 22°C and a relative atmospheric humidity of approximately 100 %.
  • the test is evaluated 5 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Example I in vivo preventive test on Leptosphaeria nodorum (wheat)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the test is evaluated 7-9 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100% means that no disease is observed.
  • Example E-12 disclosed in international patent WO-2008/101976 corresponds to N-cyclopropyl-5-fluoro-
  • Example J in vivo preventive test on Uromyces appendiculatus (beans)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are then placed in a greenhouse at approximately 21 °C and a relative atmospheric humidity of approximately 90 %.
  • the test is evaluated 10 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Example K in vivo preventive test on Puccinia triticina (wheat)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
  • the plants are placed in the greenhouse at a temperature of approximately 20°C and a relative atmospheric humidity of approximately 80 %.
  • the test is evaluated 8 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
  • Example E-13 disclosed in international patent WO-2008/101976 corresponds to N-cyclopropyl-N-[4-(3,4- dichlorophenyl)butan-2-yl]-5-fluoro-1 ,3-dimethyl-1 H-pyrazole-4-carboxamide.
  • Example 18 disclosed in international patent WO-2010/012795 corresponds to N-cyclopropyl-N-[1-(2,4- dichlorophenoxy)propan-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
  • Example 16 disclosed in international patent WO-2010/094666 corresponds to N-(2-benzylcyclohexyl)-N- cyclopropyl-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
  • the des-fluoro analogue compound CMP2 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-(3- phenylcyclohexyl)-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP3 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-(3-phenylcyclohexyl)-1 H-pyrazole-4- carboxamide.
  • the des-fluoro analogue compound CMP4 corresponds to N-[1 , 1 '-bi(cyclohexyl)-2-yl]-5-fluoro-1 ,3- dimethyl-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP5 corresponds to N- [1 , 1 '-bi(cyclohexyl)-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
  • Example L in vivo preventive test on Botrytis cinerea (beans)
  • Emulsifier 1 part by weight of alkylaryl polyglycol ether
  • active compound 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

Abstract

The present invention relates to fungicidal N-[(het)arylalkyl)] pyrazolecarboxamide or thiocarboxamide and their heterosubstituted analogues, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions.

Description

N-[(HET)ARYLALKYL)] PYRAZOLE(THIO)CARBOXAMIDES AND
THEIR HETEROSUBSTITUTED ANALOGUES
The present invention relates to fungicidal N-[(het)arylalkyl)] pyrazolecarboxamide or thiocarboxamide and their heterosubstituted analogues, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions. In international patent applications WO-2008/003746 and WO-2010/015681 certain fungicidal pyrazolecarboxamide derivatives are generically embraced in a broad disclosure of numerous compounds of the following formula :
Figure imgf000002_0001
wherein A represents a substituted 5-membered heterocyclic group that can represent various rings among which a pyrazole ring, Z can represent a hydrogen atom, an alkyl group or a cycloalkyl group and the substituted or non-substituted 2-pyridyl group is linked to the pyrazolecarboxamide moeity by means of a 3- or 4-atoms linker. However, there is no explicite disclosure or suggestion to select in these documents of any such derivative wherein A represent a 1-alkyl -3-(difluoro or dichloro)methyl-5-(chloro or fluoro)-4-pyrazolyl group.
In international patent applications WO-2008/101976, WO-2009/012998, WO-2009/127718, WO- 2009/127722, WO-2009/127726, WO-2010/012795, WO-2010/063700, WO-2010/106071 and WO-201 1/ 045355 certain fungicidal pyrazole-carboxamide derivatives are generically embraced in a broad disclosure of numerous compounds of the following formula :
Figure imgf000002_0002
wherein A represents a substituted 5-membered heterocyclic group that can represent various rings among which a pyrazole ring, Z can represent a hydrogen atom, an alkyl group, an alkoxy group or a cycloalkyl group and Ar can represent a substituted or non-substituted phenyl or naphthyl group which is linked to the pyrazolecarboxamide moeity by means of a 3-, 4- or 5-atoms linker. However, there is no explicite disclosure or suggestion to select in these documents of any such derivative wherein A represent a 1-alkyl-3-(difluoro or dichloro)methyl-5-(chloro or fluoro)-4-pyrazolyl group.
In international patent applications WO-1998/003486, WO-2006/061215, WO-2007/0039615 and WO- 2008/081017 certain fungicidal pyrazolecarboxamide derivatives are generically embraced in a broad disclosure of numerous compounds of the following formula :
Figure imgf000003_0001
wherein A represents a substituted 5-membered heterocyclic group that can represent various rings among which a pyrazole ring, Z can represent a hydrogen atom, an alkyl group or a cycloalkyl group and W can represent various substituted or non-substituted groups among which an alkyl group, a cycloalkylgroup, a trialkylsilyl group or a alkynyl group which are linked to the pyrazolecarboxamide moeity by means of a 2-, 3- or 4-atoms linker. However, there is no explicite disclosure or suggestion to select in these documents of any such derivative wherein A represent a 1 -alkyl -3-(difluoro or dichloro)methyl-5-(chloro or fluoro)-4-pyrazolyl group.
It is always of high-interest in the field of agrochemicals to use pesticidal compounds more active than the compounds already known by the man ordinary skilled in the art whereby reduced amounts of compound can be used whilst retaining equivalent efficacy.
Furthermore, the provision of new pesticidal compounds with a higher efficacy strongly reduces the risk of appearance of resistant strains in the fungi to be treated.
We have now found a new family of compounds which show enhanced fungicidal activity over the general known family of such compounds.
Accordingly, the present invention provides a N-[(het)arylalkyl)] pyrazolecarboxamide or thiocarboxamide derivative of formula (I)
Figure imgf000003_0002
wherein
• X1 and X2 which can be the same or different, represent a halogen atom ;
• Y represents a Ci-C4-alkyl ;
• T represents O or S ;
• Q represents CR R2 ; -CR3=CR4- ; -CR3=N-0- ; or -C(=W)- ;
• Q2, Q3 and Q4 , which can be the same or different, represent a direct bond ; CR R2 ; -CR3=CR4- ;
-C≡C- ; -CR3=N-0- ; -0-N=CR3- ; O ; S ; SO ; S02 ; NR5 ; SiR6R7 ; or -C(=U)-;
• B represents a phenyl ring that can be susbtituted by up to 5 groups X which can be the same or different ; a naphthyl ring that can be susbtituted by up to 7 groups X which can be the same or different ; a saturated, partially saturated or unsaturated, monocyclic or fused bicyclic 4-, 5-, 6-, 7- , 8-, 9-, 10-membered ring comprising from 1 up to 4 heteroaroms selected in the list consisting of N, O, S, that can be substituted by up to 6 groups X which can be the same or different ; a hydrogen atom ; a halogen atom ; a substituted or non-substituted Ci-Ci2-alkyl group ; a C1-C12- halogenoalkyl group having 1 to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C8-cycloalkyl group ; a substituted or non-substituted C3-C8-cycloalkenyl group, a bicyclo[2.2.1]heptan-2-yl group ; a tri(Ci-C8-alkyl)silyl group ; a substituted or non- substituted C2-C12 alkenyl group ; or a substituted or non-substituted C2-Ci2 alkynyl group ;
X represents a halogen atom ; nitro ; cyano ; isonitrile ; hydroxy ; amino ; sulfanyl ; pentafluoro-λ6- sulfanyl ; formyl ; formyloxy ; formylamino ; substituted or non-substituted (hydroxyimino)-Ci-C8- alkyl ; substituted or non-substituted (Ci-C8-alkoxyimino)-Ci-C8-alkyl ; substituted or non- substituted (C2-C8-alkenyloxyimino)-Ci-C8-alkyl ; substituted or non-substituted (C2-C8- alkynyloxyimino)-Ci-C8-alkyl ; substituted or non-substituted (benzyloxyimino)-Ci-C8-alkyl ; carboxy ; carbamoyl ; N-hydroxycarbamoyl ; carbamate ; substituted or non-substituted Ci-C8- alkyl ; Ci-C8-halogenoalkyl having 1 to 5 halogen atoms ; substituted or non-substituted C2-C8- alkenyl ; C2-C8-halogenoalkenyl having 1 to 5 halogen atoms ; substituted or non-substituted C2- C8-alkynyl ; C2-C8-halogenoalkynyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkoxy ; Ci-C8-halogenoalkoxy having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylsulfanyl ; Ci-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci -C8-al ky Is u If i ny I ; Ci-C8-halogenoalkylsulfinyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylsulfonyl ; Ci-C8-halogenoalkylsulfonyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylamino ; substituted or non-substituted di-Ci-C8-alkylamino ; substituted or non-substituted C2-C8-alkenyloxy ; C2-C8-halogenoalkenyloxy having 1 to 5 halogen atoms ; substituted or non-substituted C3-C8-alkynyloxy ; C2-C8- halogenoalkynyloxy having 1 to 5 halogen atoms ; substituted or non-substituted C3-C7-cycloalkyl ; C3-C7-halogenocycloalkyl having 1 to 5 halogen atoms ; substituted or non-substituted (C3-C7- cycloalkyl)-Ci-C8-alkyl ; substituted or non-substituted (C3-C7-cycloalkyl)-C2-C8-alkenyl ; substituted or non-substituted (C3-C7-cycloalkyl)-C2-C8-alkynyl ; substituted or non-substituted tri(Ci-C8-alkyl)silyl ; substituted or non-substituted tri(Ci-C8-alkyl)silyl-Ci-C8-alkyl ; substituted or non-substituted Ci-C8-alkylcarbonyl ; Ci-C8-halogenoalkylcarbonyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylcarbonyloxy ; Ci-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylcarbonylamino ; Ci-C8- halogenoalkyl- carbonylamino having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8- alkoxycarbonyl ; Ci-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms ; substituted or non- substituted Ci-C8-alkyloxycarbonyloxy ; Ci-C8-halogenoalkoxycarbonyloxy having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylcarbamoyl ; substituted or non-substituted di-C-r C8-alkylcarbamoyl ; substituted or non-substituted Ci-C8-alkylaminocarbonyloxy ; substituted or non-substituted di-Ci-C8-alkylaminocarbonyloxy ; substituted or non-substituted N-(Ci-C8- alkyl)hydroxy carbamoyl ; substituted or non-substituted Ci-C8-alkoxycarbamoyl ; substituted or non-substituted N-(Ci-C8-alkyl)-Ci-C8-alkoxycarbamoyl ; aryl that can be susbtituted by up to 6 groups Q which can be the same or different ; Ci-C8-arylalkyl that can be susbtituted by up to 6 groups Q which can be the same or different ; C2-C8-arylalkenyl that can be susbtituted by up to 6 groups Q which can be the same or different ; C2-C8-arylalkynyl that can be susbtituted by up to 6 groups Q which can be the same or different ; aryloxy that can be susbtituted by up to 6 groups Q which can be the same or different ; arylsulfanyl that can be susbtituted by up to 6 groups Q which can be the same or different ; arylamino that can be susbtituted by up to 6 groups Q which can be the same or different ; Ci-C8-arylalkyloxy that can be susbtituted by up to 6 groups Q which can be the same or different ; Ci-C8-arylalkylsulfanyl that can be susbtituted by up to 6 groups Q which can be the same or different ; or Ci-C8-arylalkylamino that can be susbtituted by up to 6 groups Q which can be the same or different ; or
• two substituent X together with the consecutive carbon atoms to which they are linked can form a 5- or 6-membered, saturated carbocycle or saturated heterocycle, which can be substituted by up to four groups Q which can be the same or different ;
· Z represents a hydrogen atom ; a formyl group ; a substituted or non-substituted Ci-C8-alkyl ; a substituted or non substituted Ci-C8-alkoxy ; a non-substituted C3-C7-cycloalkyl or a C3-C7- cycloalkyl substituted by up to 10 atoms or groups that can be the same or different and that can be selected in the list consisting of halogen atoms, cyano, Ci-C8-alkyl, Ci-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, Ci-C8-alkoxy, Ci-C8- halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, Ci-C8- alkoxycarbonyl, Ci-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that can be the same or different, Ci-C8-alkylaminocarbonyl and di-Ci-C8-alkylaminocarbonyl ;
• R and R2 independently represent a hydrogen atom ; a halogen atom ; cyano ; substituted or non-substituted Ci-Ci2-alkyl ; substituted or non-substituted C2-Ci2-alkenyl ; substituted or non- substituted C2-Ci2-alkynyl ; substituted or non-substituted C3-C7-cycloalkyl ; Ci-Ci2-halogenoalkyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkoxy ; substituted or non- substituted Ci-C8-alkylsulfanyl ; substituted or non-substituted Ci-C8-alkylamino ; substituted or non-substituted di-(Ci-C8-alkyl)amino ; or substituted or non-substituted Ci-C8-alkoxycarbonyl ; or R and R2 are a C2-C5-alkylene group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl or
Ci-C2-halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ; or
• The R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form a 3-, 4-, 5-, -6 or 7-membered saturated carbocycle that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of halogen atoms,
Ci-C8-alkyl or Ci-C2-halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ; or
• The R substituent of the group Q' and the R substituent of the group Ql+2, i being an integer between 1 and 2, together with the consecutive carbon atoms to which they are linked can form a 3-, 4-, 5-, 6- or 7-membered saturated carbocycle that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl or Ci-C2-halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ;
• R3 and R4 independently represent a hydrogen atom ; substituted or non-substituted Ci-C8-alkyl ; substituted or non-substituted C2-C8-alkenyl ; substituted or non-substituted C2-C8-alkynyl ; substituted or non-substituted C3-C7-cycloalkyl ; or Ci-C8-halogenoalkyl having 1 to 5 halogen atoms ; R5 represents a hydrogen atom ; a substituted or non-substituted Ci-C8-alkyl ; a C-|-C8- halogenoalkyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C2-C8-alkenyl ; a C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C8-alkynyl ; a C3-C8- halogenoalkynyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C7-cycloalkyl ; a C3-C7-halogeno-cycloalkyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C7- cycloalkyl-Ci-C8-alkyl ; formyl ; a substituted or non-substituted Ci-C8-alkylcarbonyl ; Ci-C8- halogenoalkylcarbonyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted Ci-C8-alkoxycarbonyl ; Ci-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted Ci-C8- alkylsulphonyl ; Ci-C8-halogenoalkylsulphonyl comprising up to 9 halogen atoms that can be the same or different ; phenylmethylene that can be substituted by up to 7 groups Q which can be the same or different ; or phenylsulphonyl that can be substituted by up to 5 groups Q which can be the same or different ;
• R6 and R7 independently represent a substituted or non-substituted Ci-C8-alkyl ;
• W represents O ; or S ;
• U represents O ; S ; N-ORa ; or N-CN ;
• Ra represents a hydrogen atom ; a substituted or non-substituted Ci-C4-alkyl ; or a Ci-C4- halogenoalkyl comprising up to 7 halogen atoms that can be the same or different ;
• Q independently represents a halogen atom ; cyano ; nitro ; substituted or non-substituted Ci-C8- alkyl ; Ci-C8-halogenoalkyl having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C8-alkoxy ; Ci-C8-halogenoalkoxy having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C8-alkylsulfanyl ; Ci-C8- halogenoalkylsulfanyl having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted tri(Ci-C8)alkylsilyl ; substituted or non-substituted tri(Ci-C8)alkylsilyl-Ci-C8-alkyl ; substituted or non-substituted (Ci-C8-alkoxyimino)-Ci-C8-alkyl ; substituted or non-substituted (benzyloxyimino)-Ci-C8-alkyl ;
with the provisio that -Q -Q2-Q3-Q4- does not represent CR R2 when B represents a substituted or non- substituted phenyl, naphthyl or 2-pyridyl ring ;
or that -Q -Q2-Q3-Q4- does not represent [CR R2]2 or CR R2-C(=W)- or a cycloalkyl-1 ,2-diyl group, when B represents a substituted or non-substituted phenyl, naphthyl or heterocyclic ring ;
or that Z does not represent a hydrogen atom when -Q -Q2- represents a unsubstituted cyclohexyl-1 ,2- diyl group and -Q3-Q4- represents a substituted or non-substituted cyclopropyl-1 ,2-diyl group ;
as well as its salts, N-oxydes, metallic complexes, metalloidic complexes and optically active isomers.
For the compounds according to the invention, the following generic terms are generally used with the following meanings:
• halogen means fluorine, bromine, chlorine or iodine,
carboxy means -C(=0)OH ; carbonyl means -C(=0)- ;
carbamoyl means -C(=0)NH2 ;
N-hydroxycarbamoyl means -C(=0)NHOH ;
SO represents a sulfoxyde group ;
S02 represents a sulfone group ;
• an alkyl group, an alkenyl group and an alkynyl group as well as moieties containing these terms, can be linear or branched;
• the aryl moeity contained in an aryl group, an arylalkyl group, an arylalkenyl group and an arylalkynyl group as well as moieties containing these terms, can be a phenyl group that can be substituted by up to 5 groups Q which can be the same or different, a naphthyl group that can be substituted by up to 7 groups Q which can be the same or different or a pyridyl group that can be substituted by up to 4 groups Q which can be the same or different ;
• and, heteroatom means sulphur, nitrogen or oxygen.
• in the case of an amino group or the amino moiety of any other amino-comprising group, substituted by two substituent that can be the same or different, the two substituent together with the nitrogen atom to which they are linked can form a heterocyclyl group, preferably a 5- to 7- membered heterocyclyl group, that can be substituted or that can include other hetero atoms, for example a morpholino group or piperidinyl group.
• unless indicated otherwise, a group or a substituent that is substituted according to the invention can be substituted by one or more of the following groups or atoms: a halogen atom, a nitro group, a hydroxy group, a cyano group, an amino group, a sulfanyl group, a pentafluoro-λ6- sulfanyl group, a formyl group, a formyloxy group, a formylamino group, a carbamoyl group, a N- hydroxycarbamoyl group, a carbamate group, a (hydroxyimino)-Ci-C6-alkyl group, a Ci-C8-alkyl, a tri(Ci-C8-alkyl)silyl-Ci-C8-alkyl, Ci-C8-cycloalkyl, tri(Ci-C8-alkyl)silyl-Ci-C8-cycloalkyl, a Ci-C8- halogenoalkyl having 1 to 5 halogen atoms, a Ci-C8-halogenocycloalkyl having 1 to 5 halogen atoms, a C2-C8-alkenyl, a C2-C8-alkynyl, a C2-C8-alkenyloxy, a C2-C8-alkynyloxy, a Ci-C8- alkylamino, a di-Ci-C8-alkylamino, a Ci-C8-alkoxy, a Ci-C8-halogenoalkoxy having 1 to 5 halogen atoms, a Ci-C8-alkylsulfanyl, a Ci-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, a C2-C8- alkenyloxy, a C2-C8-halogenoalkenyloxy having 1 to 5 halogen atoms, a C3-C8-alkynyloxy, a C3- C8-halogenoalkynyloxy having 1 to 5 halogen atoms, a Ci-C8-alkylcarbonyl, a Ci-C8- halogenoalkylcarbonyl having 1 to 5 halogen atoms, a Ci-C8-alkylcarbamoyl, a di-C-|-C8- alkylcarbamoyl, a N-Ci-C8-alkyloxycarbamoyl, a Ci-C8-alkoxycarbamoyl, a N-Ci-C8-alkyl-Ci-C8- alkoxycarbamoyl, a Ci-C8-alkoxycarbonyl, a Ci-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms, a Ci-C8-alkylcarbonyloxy, a Ci-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, a Ci-C8-alkylcarbonylamino, a Ci-C8-halogenoalkylcarbonylamino having 1 to 5 halogen atoms, a Ci-C8-alkylaminocarbonyloxy, a di-Ci-C8-alkylaminocarbonyloxy, a Ci-C8-alkyloxycarbonyloxy, a Ci-C8-alkylsulfinyl, a Ci-C8-halogenoalkylsulfinyl having 1 to 5 halogen atoms, a Ci-C8- alkylsulfonyl, a Ci-C8-halogenoalkylsulfonyl having 1 to 5 halogen atoms, a Ci-C8- alkylaminosulfamoyl, a di-Ci-C8-alkylaminosulfamoyl, a (Ci-C6-alkoxyimino)-Ci-C6-alkyl, a (Ci-C6- alkenyloxyimino)-Ci-C6-alkyl, a (Ci-C6-alkynyloxyimino)-Ci-C6-alkyl, a 2-oxopyrrolidin-1-yl, (benzyloxyimino)-Ci-C6-alkyl, Ci-C8-alkoxyalkyl, Ci-C8-halogenoalkoxyalkyl having 1 to 5 halogen atoms, benzyloxy, benzylsulfanyl, benzylamino, phenoxy, phenylsulfanyl, or phenylamino.
Any of the compounds of the present invention can exist in one or more optical or chiral isomer forms depending on the number of asymmetric centres in the compound. The invention thus relates equally to all the optical isomers and to their racemic or scalemic mixtures (the term "scalemic" denotes a mixture of enantiomers in different proportions) and to the mixtures of all the possible stereoisomers, in all proportions. The diastereoisomers and/or the optical isomers can be separated according to the methods which are known per se by the man ordinary skilled in the art.
Any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the number of double bonds in the compound. The invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions. The geometric isomers can be separated according to general methods, which are known per se by the man ordinary skilled in the art. Any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the relative position (syn/anti or cis/trans) of the substituents of ring B. The invention thus relates equally to all syn/anti (or cis/trans) isomers and to all possible syn/anti (or cis/trans) mixtures, in all proportions. The syn/anti (or cis/trans) isomers can be separated according to general methods, which are known per se by the man ordinary skilled in the art.
Any of the compounds of formula (I) wherein X represents a hydroxy, a sulfanyl group or an amino group may be found in its tautomeric form resulting from the shift of the proton of said hydroxy, sulfanyl or amino group. Such tautomeric forms of such compounds are also part of the present invention. More generally speaking, all tautomeric forms of compounds of formula (I) wherein X represents a hydroxy, a sulfanyl group or an amino group, as well as the tautomeric forms of the compounds which can optionally be used as intermediates in the preparation processes and which will be defined in the description of these processes, are also part of the present invention.
Preferred compounds according to the invention are compounds of formula (I) wherein X1 and X2 independently represent a chlorine or a fluorine atom. More preferred compounds according to the invention are compounds of formula (I) wherein X1 and X2 represent a fluorine atom ;
Other preferred compounds according to the invention are compounds of formula (I) wherein Y represents methyl ;
Other preferred compounds according to the invention are compounds of formula (I) wherein T represents
O ;
Other preferred compounds according to the invention are compounds of formula (I) wherein B represents a substituted or non-substituted phenyl ring ; a substituted or non-substituted naphthyl ring ; a substituted or non-substituted pyridyl ring ; a substituted or non-substituted thienyl ring ; or a substituted or non-substituted benzothienyl ring ; more preferred compounds according to the invention are compounds of formula (I) wherein B represents a substituted or non-substituted phenyl ring ; other more preferred compounds according to the invention are compounds of formula (I) wherein B represents a substituted or non-substituted 2-pyridyl ring ;
Other preferred compounds according to the invention are compounds of formula (I) wherein X independently represents a halogen atom ; substituted or non-substituted Ci-C8-alkyl ; C-|-C8- halogenoalkyl comprising up to 9 halogen atoms that can be the same or different ; substituted or non- substituted tri(Ci-C8-alkyl)silyl ; substituted or non-substituted C-rC8-alkoxy or Ci-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C8- alkylsulfanyl or Ci-C8-halogenoalkylsulfanyl comprising up to 9 halogen atoms that can be the same or different ; or wherein two consecutive substituents X together with the phenyl ring form a substituted or non-substituted cyclopentyl or cyclohexyl ring ;
Even more preferred compounds according to the invention are compounds of formula (I) wherein X independently represents fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, terbutyl, cyclopropyl, cyclopentyl, cyclohexyl, trimethylsilyl, methoxy, ethoxy, methylsulfanyl, ethylsulfanyl, trifluoromethyl, trichloromethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethysulfanyl, trifluoromethylsulfanyl and difluorochloro- methylsulfanyl ;
Other preferred compounds according to the invention are compounds of formula (I) wherein Z represents a hydrogen atom ; a non-substituted C3-C7 cycloalkyl ; or a C3-C7 cycloalkyl substituted by up to 10 groups or atoms that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl, Ci-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, Ci-C8-alkoxy and Ci-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different ; more preferably Z represents a non-substituted C3-C7-cycloalkyl. ; even more preferably Z represents cyclopropyl ;
Other preferred compounds according to the invention are compounds of formula (I) wherein Q represents CR R2 ; Other preferred compounds according to the invention are compounds of formula (I) wherein Q2, Q3 and Q4, which can be the same or different, represents a direct bond ; CR R2 ; or O ;
More preferred compounds according to the invention are compounds of formula (I) wherein Q2 represents CR R2 and Q3 and Q4 represent a direct bond ;
Other more preferred compounds according to the invention are compounds of formula (I) wherein Q2 represents CR R2 and Q3 represents O and Q4 represent a direct bond ;
Other preferred compounds according to the invention are compounds of formula (I) wherein R and R2 independently represent a hydrogen atom, a fluorine atom, a substituted or non-substituted Ci-C8-alkyl or a substituted or non-substituted Ci-C8-alkoxy ;
Other preferred compounds according to the invention are compounds of formula (I) wherein the R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form an optionally mono or polysubstituted 3-, 4-, 5-, 6- or 7-membered saturated carbocycle ; more preferably an optionally mono or polysubstituted cyclopropyl, cyclopentyl, cyclohexyl or a cycloheptyl ring ; even more preferably a cyclopropyl, a cyclopentyl or a cyclohexyl ring ;
Other more preferred compounds according to the invention are compounds of formula (I) wherein the R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form an cyclopentyl group that can be substituted by up to three groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
Other more preferred compounds according to the invention are compounds of formula (I) wherein the R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form an cyclohexyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
Other more preferred compounds according to the invention are compounds of formula (I) wherein the R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form an cycloheptyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
Even more prefered compounds according to the invention are compounds of formula (I) wherein -Q -Q2- represents an optionally mono or polysubstituted cyclopentyl-1 ,2-diyl, cyclohexyl-1 ,2-diyl or cycloheptyl- 1 ,2-diyl group and -Q3-Q4-B represents a bicyclo[2.2.1]heptan-2-yl group, A1 , A2, A3 or A4 wherein
Figure imgf000010_0001
A represents , wherein
Ra represents hydrogen, Ci-C4-alkyl or Ci-C4-haloalkyl ;
Z represents -CRa2Ra3Ra4 or -Si Ra2Ra3Ra4 ;
s represents 0, 1 , 2 or 3 ;
t represents 0 or 1 ;
Ra2, Ra3, Ra4 independently of one another represent hydrogen, halogen Ci-C4-alkyl or Ci-C4- haloalkyl ;
Ra3 and Ra4 furthermore together with the carbon atom to which they are attached, can form an optionally substituted saturated or insaturated 3- to 6-membered carbocyclic ring ;
Particulary preferably,
Ra represents hydrogen or methyl ; s represents 0 or 1 ;
Ra2 represents chlorine, methyl, ethyl, isopropyl or trifluoromethyl;
Ra3 represents chlorine, methyl, ethyl, isopropyl or trifluoromethyl;
Ra4 represents hydrogen, chlorine, methyl, ethyl, isopropyl or trifluoromethyl;
Figure imgf000011_0001
A2 represents , wherein
Ra6 represent hydrogen, halogen, Ci-C8-alkyl or d-Cs-haloalkyl ;
Ra5, Ra7, Ra8 independently of one another represent hydrogen, methyl or ethyl Particulary preferably,
Ra5 represents hydrogen or methyl ;
Ra6 represents hydrogen ;
Ra7 represents hydrogen or methyl ;
Ra8 represents fluorine, chlorine, methyl, ethyl or trifluoromethyl ;
Figure imgf000011_0002
, wherein
Ra represent hydrogen or fluorine ;
A4 represents
Figure imgf000011_0003
, wherein
Ra ° represent optionally substituted C2-Ci2-alkyl, optionally substituted C2-C-i2-alkenyl, optionally substituted C2-Ci2-alkynyl, optionally substituted C3-C8-cycloalkyl, optionally substituted phenyl or heterocyclyl ;
Ra 1 represent hydrogen or halogen ;
Ra 2 represent hydrogen or halogen ;
Particulary preferably,
Ra ° represents ethyl, propyl, isopropyl, butyl, secbutyl, terbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, a-methylcyclopropyl, 4-fluorophenyl, 4-bromophenyl, 2-thienyl, 3-thienyl or 2-fury;
Ra 1 represents hydrogen ;
Ra 2 represents hydrogen ;
Other preferred compounds according to the invention are compounds of formula (I) wherein the R1 substituent of the group Q' and the R1 substituent of the group Ql+2, i being an integer between 1 and 2, together with the consecutive carbon atoms to which they are linked can form an optionally mono or polysusbtituted 4-, 5-, 6- or 7-membered saturated carbocycle ; more preferably an optionally mono or polysusbtituted cyclopentyl, cyclohexyl or a cycloheptyl ring ; even more preferably a cyclohexyl ring ;
Other more preferred compounds according to the invention are compounds of formula (I) wherein the R substituent of the group Q' and the R substituent of the group QL+2, i being an integer between 1 and 2, together with the consecutive carbon atoms to which they are linked can form an cyclohexyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl ;
Even more prefered compounds according to the invention are compounds of formula (I) wherein -Q -Q2- Q3- represents an optionally mono or polysubstituted cyclohexyl-1 ,3-diyl and -Q4-B represents a bicyclo[2.2.1]heptan-2-yl group, or a A1 , A2, A3 or A4 group as defined above. Other preferred compounds according to the invention are compounds of formula (I) wherein R3 and R4 independently represent a hydrogen atom, or a substituted or non-substituted Ci-C8-alkyl;
Other preferred compounds according to the invention are compounds of formula (I) wherein R5 represents a substituted or non-substituted Ci-C8-alkyl ;
Other preferred compounds according to the invention are compounds of formula (I) wherein R6 and R7 independently represent a non-substituted Ci-C8-alkyl ;
More preferably, R6 and R7 independently represent a non-substituted Ci-C3-alkyl ;
Even more preferably, R6 and R7 represent methyl
Other preferred compounds according to the invention are compounds of formula (I) wherein U represents O.
Other preferred compounds according to the invention are compounds of formula (I) wherein U represents N-0-(Ci-C4-alkyl).
The above mentioned preferences with regard to the substituents of the compounds according to the invention can be combined in various manners. These combinations of preferred features thus provide sub-classes of compounds according to the invention. Examples of such sub-classes of preferred compounds according to the invention can be combined:
- preferred features of X1 with preferred features of X2, Y, T, B, Z , Q , Q2, Q3, Q4, R1 , R2, R3, R4, R5, R6, R7, X and U;
- preferred features of X2 with preferred features of X1 , Y, T, B, Z , Q , Q2, Q3, Q4, R1 , R2, R3, R4, R5, R6, R7, X and U;
- preferred features of Y with preferred features of X1 , X2, T, B, Z Q a2, a3, a4, R1 , R2, R3, R4, R5, R6, R7, X and U;
- preferred features of T with preferred features of X1 , X2, Y, B, Z Q a2, a3, a4, R1 , R2, R3, R4, R5, R6, R7, X and U; - preferred features of B with preferred features of X1, X2, Y, T, Z Q , Q2, Q3, Q4, R , R2, R3, R4, R5, R6,
R7, X and U;
- preferred features of Z with preferred features of X , X2, Y, T, B, Q , Q2, Q3, Q4, R , R2, R3, R4, R5, R6,
R7, X and U;
- preferred features of Q with preferred features of X1 , X2 , Y, T, B, Z1 , Q2, Q3, Q4, R , R2, R3, R4, R5, R6, R7, X and U;
- preferred features of Q2 with preferred features of X1 , X2 , Y, T, B, Z1 , Q1, Q3, Q4, R , R2, R3, R4, R5, R6,
R7, X and U;
- preferred features of Q3 with preferred features of X1 , X2 , Y, T, B, Z1 , Q1, Q2, Q4, R , R2, R3, R4, R5, R6,
R7, X and U;
- preferred features of Q4 with preferred features of X1 , X2 , Y, T, B, Z1 , Q1, Q2, Q3, R1, R2, R3, R4, R5, R6,
R7, X and U;
- preferred features of R with preferred features of X1 , X2, Y, T, B, Z1 , Q1, Q2, Q3, Q4, R2, R3, R4, R5, R6,
R7, X and U;
- preferred features of R2 with preferred features of X1 , X2, Y, T, B, Z1 , Q\ Q2, Q3, Q4, R1, R3, R4, R5, R6, R7, X and U;
- preferred features of R3 with preferred features of X1 , X2, Y, T, B, Z1 , Q1, Q2, Q3, Q4, R1, R2, R4, R5, R6,
R7, X and U;
- preferred features of R4 with preferred features of X1 , X2, Y, T, B, Z1 , Q1, Q2, Q3, Q4, R1, R2, R3, R5, R6,
R7, X and U;
- preferred features of R5 with preferred features of X1 , X2, Y, T, B, Z1 , Q1, Q2, Q3, Q4, R1, R2, R3, R4, R6,
R7, X and U;
- preferred features of R6 with preferred features of X1 , X2, Y, T, B, Z1 , Q1, Q2, Q3, Q4, R1, R2, R3, R4, R5,
R7, X and U;
- preferred features of R7 with preferred features of X1 , X2, Y, T, B, Z1 , Q1, Q2, Q3, Q4, R1, R2, R3, R4, R5, R6, X and U;
- preferred features of X with preferred features of X1, X2, Y, T, B, Z Q1, Q2, Q3, Q4, R1, R2, R3, R4, R5,
R6, R7 and U;
- preferred features of U with preferred features of X1, X2, Y, T, B, Z Q1, Q2, Q3, Q4, R1, R2, R3, R4, R5, R6, R7, and X;
In these combinations of preferred features of the substituents of the compounds according to the invention, the said preferred features can also be selected among the more preferred features of each of X1, X2, Y, T, B, Z Q a2, a3, a4, R1, R2, R3, R4, R5, R6, R7, X and U, so as to form most preferred subclasses of compounds according to the invention.
The present invention also relates to a process for the preparation of the compound of formula (I).
Thus, according to a further aspect of the present invention there is provided a process P1 for the preparation of a compound of formula (I) as herein-defined and wherein T represents O and that comprises reacting a N-susbtituted amine derivative of formula (II) or one of its salts: -Q Q B
(II)
wherein Z , Q , Q2, Q3, Q4 and B are as herein-defined; with a carboxylic acid derivative of formula (III):
Figure imgf000014_0001
(IN)
wherein X1 , X2 and Y are as herein-defined and L represents a leaving group selected in the list consisting of a halogen atom, a hydroxyl group, -ORb, -OC(=0)Rb, Rb being a substituted or non- substituted Ci-Ce-alkyI, a substituted or non-substituted Ci-C6-haloalkyl, a benzyl, a 4-methoxybenzyl or a pentafluorophenyl group ; in the presence of a catalyst and in the presence of a condensing agent in case L represents a hydroxyl group, and in the presence of an acid binder in case L represents a halogen atom.
N-substituted amine derivatives of formula (II) are known or can be prepared by known processes such as reductive amination of aldehyde or ketone (Bioorganics and Medicinal Chemistry Letters (2006), 2014), or reduction of imines (Tetrahedron (2005), 1 1689), or nucleophilic substitution of halogen, mesylate or tosylate (Journal of Medicinal Chemistry (2002), 3887).
Moreover, some amines of formula (II) are specificaly known such as :
- 2-butylcyclohexanamine can be prepared according to Tetrahedron (1976), 23, 2421 ,
- 2-(4-methylpentan-2-yl)cyclohexanamine can be prepared according to WO-2006/061215,
- 2-(4,4-dimethylpentan-2-yl)cyclohexanamine can be prepared according to WO-2006/061215,
- 2-(3-methylbutyl)cyclohexanamine can be prepared according to WO-2006/061215,
- 2-(3,3-dimethylbutyl)cyclohexanamine can be prepared according to WO-2006/061215,
- 2-[3-(trimethysilyl)propyl]cyclohexanamine can be prepared according to WO-2006/061215,
- 2-isobutylcyclohexanamine can be prepared according to Tetrahedron (1997), 53, 4935,
- 2-propylcyclohexanamine can be prepared according to Journal of Combinatorial Chemistry (2005), 7, 109.
Carboxylic acid derivatives of formula (III) can be prepared according to process P2.
In case L represents a hydroxy group, the process according to the present invention is conducted in the presence of condensing agent. Suitable condensing agent may be selected in the non limited list consisting of acid halide former, such as phosgene, phosphorous tribromide, phosphorous trichloride, phosphorous pentachloride, phosphorous trichloride oxide or thionyl chloride; anhydride former, such as ethyl chloroformate, methyl chloroformate, isopropyl chloroformate, isobutyl chloroformate or methanesulfonyl chloride; carbodiimides, such as Ν,Ν'-dicyclohexylcarbodiimide (DCC) or other customary condensing agents, such as phosphorous pentoxide, polyphosphoric acid, N,N'-carbonyl- diimidazole, 2-ethoxy-N-ethoxycarbonyl-1 ,2-dihydroquinoline (EEDQ), triphenylphosphine/tetrachloro- methane, 4-(4,6-dimethoxy[1 .3.5]-triazin-2-yl)-4-methylmorpholinium chloride hydrate or bromo- tripyrrolidino-phosphonium-hexafluorophosphate.
The process according to the present invention is conducted in the presence of a catalyst. Suitable catalyst may be selected in the list consisting of 4-dimethyl-aminopyridine, 1-hydroxy-benzotriazole or dimethylformamide.
In case L represents a halogen atom, the process according to the present invention is conducted in the presence of an acid binder. Suitable acid binders for carrying out process P1 according to the invention are in each case all inorganic and organic bases that are customary for such reactions. Preference is given to using alkaline earth metal, alkali metal hydride, alkali metal hydroxides or alkali metal alkoxides, such as sodium hydroxide, sodium hydride, calcium hydroxide, potassium hydroxide, potassium tert- butoxide or other ammonium hydroxide, alkali metal carbonates, such as cesium carbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, alkali metal or alkaline earth metal acetates, such as sodium acetate, potassium acetate, calcium acetateand also tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine, N,N-dimethylaniline, pyridine, N-methylpiperidine, Ν,Ν-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclo- nonene (DBN) or diazabicycloundecene (DBU).
It is also possible to work in the absence of an additional condensing agent or to employ an excess of the amine component, so that it simultaneously acts as acid binder agent.
According to a further aspect according to the invention, there is provided a process P2 for the preparation of carboxylic acid derivatives of formula (III) wherein T represents O and illustrated according to the following reaction scheme :
Figure imgf000015_0001
(llle) (Mid)
Process P2
wherein X2 is as herein-defined
5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbaldehyde is known from WO-2004/014138 (reference example 35). Step 1 of process P2 is performed in the presence of an oxidant, and if appropriate in the presence of a solvent.
Steps 2 and 5 of process P2 are performed in the presence of acid halide, and if appropriate in the presence of a solvent.
Step 3 of process P2 is performed in the presence of a fluorinating agent, and if appropriate in the presence of a solvent.
Step 4 of process P2 is performed in the presence of an acid or a base and if appropriate in the presence of a solvent
Suitable oxidants for carrying out step 1 of process P2 according to the invention are in each case all inorganic and organic oxidant which are customary for such reactions. Preference is given to using benzyltriethylammonium permanganate, bromine, chlorine, m-chloroperbenzoic acid, chromic acid, chromium (VI) oxide, hydrogen peroxide, hydrogen peroxide-boron trifluoride, hydrogen peroxide-urea, 2-hydroxyperoxyhexafluoro-2-propanol; Iodine, oxygen-platinum catalyst, perbenzoic acid, peroxyacetyl nitrate, potassium permanganate, potassium ruthenate, pyridinium dichromate, ruthenium (VIII) oxide, silver (I) oxide, silver (II) oxide, silver nitrite, sodium chlorite, sodium hypochlorite, or 2,2,6,6- tetramethylpiperidin-1-oxyl. Suitable acid halides for carrying out steps 2 and 5 of process P2 according to the invention are in each case all organic or inorganic acid halides which are customary for such reactions. Preference is given to using notably phosgene, phosphorous trichloride, phosphorous pentachloride, phosphorous trichloride oxide, thionyl chloride, or carbon tetrachloride-triphenylphosphine. Suitable fluorinating agent for carrying out step 3 of process P2 according to the invention is in each case all fluorinating agents which are customary for such reactions. Preference is given to using cesium fluoride, potassium fluoride, potassium fluoride-calcium difluoride, or tetrabutylammonium fluoride.
When carrying out steps 1 to 5 of process P2 according to the invention, the reaction temperatures can independently be varied within a relatively wide range. Generally, processes according to the invention are carried out at temperatures between 0°C and 160°C, preferably between 10°C and 120°C. A way to control the temperature for the processes according to the invention is to use the micro-waves technology. Steps 1 to 5 of process P2 according to the invention are generally independently carried out under atmospheric pressure. However, in each case, it is also possible to operate under elevated or reduced pressure.
When carrying out step 1 of process P2 according to the invention, generally one mole or other an excess of the oxidant is employed per mole of aldehyde of formula (IV). It is also possible to employ the reaction components in other ratios. When carrying out carrying out steps 2 and 5 of process P2 to the invention, generally one mole or other an excess of the acid halides is employed per mole of acid of formula (Ilia) or (Mid). It is also possible to employ the reaction components in other ratios.
When carrying out steps 3 of process P2 according to the invention generally one mole or other an excess of fluorinating agent is employed per mole of acid chloride (1Mb). It is also possible to employ the reaction components in other ratios.
When carrying out steps 4 of process P2 according to the invention generally one mole or other an excess of acid or base is employed per mole of acid fluoride (lllc). It is also possible to employ the reaction components in other ratios.
According to a further aspect according to the invention, there is provided a process P3 for the preparation of a compound of formula (I) wherein T represents S, starting from a compound of formula (I) wherein T represents O and illustrated according to the following reaction scheme :
Figure imgf000017_0001
Process P3
wherein X1 , X2, Y, Z , Q , Q2, Q3, Q4 and B are as herein-defined, in the optional presence of a catalytic or stoechiometric or more, quantity of a base such as an inorganic and organic base. Preference is given to using alkali metal carbonates, such as sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate ; heterocyclic aromatic bases, such as pyridine, picoline, lutidine, collidine ; and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, Ν,Ν-dimethylaniline, N,N-dimethyl- aminopyridine or N-methyl-piperidine.
Process P3 according to the invention is performed in the presence of a thionating agent. Starting amide derivatives of formula (I) can be prepared according to processes P1.
Suitable thionating agents for carrying out process P3 according to the invention can be sulphur (S), sulfhydric acid (H2S), sodium sulfide (Na2S), sodium hydrosulfide (NaHS), boron trisulfide (B2S3), bis(diethylaluminium) sulfide ((AIEt2)2S), ammonium sulfide ((NH4)2S), phosphorous pentasulfide (P2S5), Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1 ,2,3,4-dithiadiphosphetane 2,4-disulfide) or a polymer- supported thionating reagent such as described in Journal of the Chemical Society, Perkin 1 (2001 ), 358. The compound according to the present invention can be prepared according to the general processes of preparation described above. It will nevertheless be understood that, on the basis of his general knowledge and of available publications, the skilled worker will be able to adapt this method according to the specifics of each of the compounds, which it is desired to synthesize.
In a further aspect, the present invention also relates to a fungicide composition comprising an effective and non-phytotoxic amount of an active compound of formula (I).
The expression "effective and non-phytotoxic amount" means an amount of composition according to the invention that is sufficient to control or destroy the fungi present or liable to appear on the cropsand that does not entail any appreciable symptom of phytotoxicity for the said crops. Such an amount can vary within a wide range depending on the fungus to be controlled, the type of crop, the climatic conditions and the compounds included in the fungicide composition according to the invention. This amount can be determined by systematic field trials that are within the capabilities of a person skilled in the art. Thus, according to the invention, there is provided a fungicide composition comprising, as an active ingredient, an effective amount of a compound of formula (I) as herein defined and an agriculturally acceptable support, carrier or filler.
According to the invention, the term "support" denotes a natural or synthetic, organic or inorganic compound with that the active compound of formula (I) is combined or associated to make it easier to apply, notably to the parts of the plant. This support is thus generally inert and should be agriculturally acceptable. The support can be a solid or a liquid. Examples of suitable supports include clays, natural or synthetic silicates, silica, resins, waxes, solid fertilisers, water, alcohols, in particular butanol, organic solvents, mineral and plant oils and derivatives thereof. Mixtures of such supports can also be used.
The composition according to the invention can also comprise additional components. In particular, the composition can further comprise a surfactant. The surfactant can be an emulsifier, a dispersing agent or a wetting agent of ionic or non-ionic type or a mixture of such surfactants. Mention can be made, for example, of polyacrylic acid salts, lignosulphonic acid salts, phenolsulphonic or naphthalenesulphonic acid salts, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (in particular alkylphenols or arylphenols), salts of sulphosuccinic acid esters, taurine derivatives (in particular alkyl taurates), phosphoric esters of polyoxyethylated alcohols or phenols, fatty acid esters of polyolsand derivatives of the above compounds containing sulphate, sulphonate and phosphate functions. The presence of at least one surfactant is generally essential when the active compound and/or the inert support are water-insoluble and when the vector agent for the application is water. Preferably, surfactant content can be comprised from 5% to 40% by weight of the composition.
Optionally, additional components can also be included, e.g. protective colloids, adhesives, thickeners, thixotropic agents, penetration agents, stabilisers, sequestering agents. More generally, the active compounds can be combined with any solid or liquid additive, that complies with the usual formulation techniques. In general, the composition according to the invention can contain from 0.05 to 99% by weight of active compound, preferably 10 to 70% by weight.
Compositions according to the invention can be used in various forms such as aerosol dispenser, capsule suspension, cold fogging concentrate, dustable powder, emulsifiable concentrate, emulsion oil in water, emulsion water in oil, encapsulated granule, fine granule, flowable concentrate for seed treatment, gas (under pressure),gas generating product, granule, hot fogging concentrate, macrogranule, microgranule, oil dispersible powder, oil miscible flowable concentrate, oil miscible liquid, paste, plant rodlet, powder for dry seed treatment, seed coated with a pesticide, soluble concentrate, soluble powder, solution for seed treatment, suspension concentrate (flowable concentrate), ultra low volume (ULV) liquid, ultra low volume (ULV) suspension, water dispersible granules or tablets, water dispersible powder for slurry treatment, water soluble granules or tablets, water soluble powder for seed treatment and wettable powder. These compositions include not only compositions that are ready to be applied to the plant or seed to be treated by means of a suitable device, such as a spraying or dusting device, but also concentrated commercial compositions that must be diluted before application to the crop.
The compounds according to the invention can also be mixed with one or more insecticide, fungicide, bactericide, attractant, acaricide or pheromone active substance or other compounds with biological activity. The mixtures thus obtained have normally a broadened spectrum of activity. The mixtures with other fungicide compounds are particularly advantageous.
Examples of suitable fungicide mixing partners can be selected in the following lists:
(1 ) Inhibitors of the ergosterol biosynthesis, for example (1.1 ) aldimorph (1704-28-5), (1 .2) azaconazole
(60207-31-0), (1 .3) bitertanol (55179-31-2), (1.4) bromuconazole (1 16255-48-2), (1 .5) cyproconazole (1 13096-99-4), (1 .6) diclobutrazole (75736-33-3), (1.7) difenoconazole (1 19446-68-3), (1.8) diniconazole (83657-24-3), (1.9) diniconazole-M (83657-18-5), (1.10) dodemorph (1593-77-7), (1.1 1 ) dodemorph acetate (31717-87-0), (1.12) epoxiconazole (106325-08-0), (1.13) etaconazole (60207-93-4), (1.14) fenarimol (60168-88-9), (1.15) fenbuconazole (1 14369-43-6), (1.16) fenhexamid (126833-17-8), (1.17) fenpropidin (67306-00-7), (1.18) fenpropimorph (67306-03-0), (1.19) fluquinconazole (136426-54-5), (1.20) flurprimidol (56425-91-3), (1.21 ) flusilazole (85509-19-9), (1.22) flutriafol (76674-21-0), (1.23) furconazole (1 12839-33-5), (1.24) furconazole-cis (1 12839-32-4), (1 .25) hexaconazole (79983-71-4), (1.26) imazalil (60534-80-7), (1.27) imazalil sulfate (58594-72-2), (1.28) imibenconazole (86598-92-7), (1.29) ipconazole (125225-28-7), (1.30) metconazole (1251 16-23-6), (1 .31 ) myclobutanil (88671-89-0), (1.32) naftifine (65472-88-0), (1.33) nuarimol (63284-71-9), (1.34) oxpoconazole (174212-12-5), (1.35) paclobutrazol (76738-62-0), (1.36) pefurazoate (101903-30-4), (1 .37) penconazole (66246-88-6), (1.38) piperalin (3478-94-2), (1.39) prochloraz (67747-09-5), (1.40) propiconazole (60207-90-1 ), (1.41 ) prothioconazole (178928-70-6), (1.42) pyributicarb (88678-67-5), (1 .43) pyrifenox (88283-41-4), (1.44) quinconazole (103970-75-8), (1.45) simeconazole (149508-90-7), (1.46) spiroxamine (1 18134-30-8), (1.47) tebuconazole (107534-96-3), (1.48) terbinafine (91 161-71-6), (1 .49) tetraconazole (1 12281-77-3), (1.50) triad imefon (43121-43-3), (1.51 ) triadimenol (89482-17-7), (1 .52) tridemorph (81412-43-3), (1.53) triflumizole (68694-1 1-1 ), (1.54) triforine (26644-46-2), (1.55) triticonazole (131983-72-7), (1.56) uniconazole (83657-22-1 ), (1 .57) uniconazole-p (83657-17-4), (1.58) viniconazole (77174-66-4), (1.59) voriconazole (137234-62-9), (1.60) 1-(4-chlorophenyl)-2-(1 H-1 ,2,4-triazol-1-yl)cycloheptanol (129586-32- 9), (1 .61 ) methyl 1-(2,2-dimethyl-2,3-dihydro-1 H-inden-1-yl)-1 H-imidazole-5-carboxylate (1 10323-95-0), (1.62) N 5-(difluoromethyl)-2-methyl-4-[3-(trimethylsilyl)propo
methylimidoformamide, (1.63) N-ethyl-N-methyl-N 2-methyl-5-(trifluoromethyl)-4-[3- (trimethylsilyl)propoxy]phenyl}imidoformamide and (1.64) 0-[1-(4-methoxyphenoxy)-3,3-dimethylbutan-2- yl] 1 H-imidazole-1-carbothioate (1 1 1226-71-2).
(2) inhibitors of the respiratory chain at complex I or II, for example (2.1 ) bixafen (581809-46-3), (2.2) boscalid (188425-85-6), (2.3) carboxin (5234-68-4), (2.4) diflumetorim (130339-07-0), (2.5) fenfuram (24691-80-3), (2.6) fluopyram (658066-35-4), (2.7) flutolanil (66332-96-5), (2.8) fluxapyroxad (907204-31-
3) , (2.9) furametpyr (123572-88-3), (2.10) furmecyclox (60568-05-0), (2.1 1 ) isopyrazam (mixture of syn- epimeric racemate 1 RS,4SR,9RS and anti-epimeric racemate 1 RS,4SR,9SR) (881685-58-1 ), (2.12) isopyrazam (anti-epimeric racemate 1 RS,4SR,9SR), (2.13) isopyrazam (anti-epimeric enantiomer 1 R,4S,9S), (2.14) isopyrazam (anti-epimeric enantiomer 1 S,4R,9R), (2.15) isopyrazam (syn epimeric racemate 1 RS,4SR,9RS), (2.16) isopyrazam (syn-epimeric enantiomer 1 R,4S,9R), (2.17) isopyrazam (syn-epimeric enantiomer 1 S,4R,9S), (2.18) mepronil (55814-41-0), (2.19) oxycarboxin (5259-88-1 ),
(2.20) penflufen (494793-67-8), (2.21 ) penthiopyrad (183675-82-3), (2.22) sedaxane (874967-67-6), (2.23) thifluzamide (130000-40-7), (2.24) 1-methyl-N-[2-(1 , 1 ,2,2-tetrafluoroethoxy)phenyl]-3- (trifluoromethyl)-1 H-pyrazole-4-carboxamide, (2.25) 3-(difluoromethyl)-1-methyl-N-[2-(1 , 1 ,2,2- tetrafluoroethoxy)phenyl]-1 H-pyrazole-4-carboxamide, (2.26) 3-(difluoromethyl)-N-[4-fluoro-2-(1 , 1 ,2,3,3,3- hexafluoropropoxy)phenyl]-1-methyl-1 H-pyrazole-4-carboxamide, (2.27) N-[1-(2,4-dichlorophenyl)-1- methoxypropan-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide (1092400-95-7) (WO 2008148570), (2.28) 5,8-difluoro-N-[2-(2-fluoro-4-{[4-(trifluoromethyl)pyridin-2- yl]oxy}phenyl)ethyl]quinazolin-4-amine (1210070-84-0) (WO2010025451 ) and (2.29) N-[9- (dichloromethylene)-1 ,2,3,4-tetrahydro-1 ,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1 H- pyrazole-4-carboxamide.
(3) inhibitors of the respiratory chain at complex III, for example (3.1 ) ametoctradin (865318-97-4), (3.2) amisulbrom (348635-87-0), (3.3) azoxystrobin (131860-33-8), (3.4) cyazofamid (1201 16-88-3), (3.5) coumethoxystrobin (850881-30-0), (3.6) coumoxystrobin (850881-70-8), (3.7) dimoxystrobin (141600-52-
4) , (3.8) enestroburin (238410-1 1-2) (WO 2004/058723), (3.9) famoxadone (131807-57-3) (WO
2004/058723), (3.10) fenamidone (161326-34-7) (WO 2004/058723), (3.1 1 ) fenoxystrobin (918162-02-4), (3.12) fluoxastrobin (361377-29-9) (WO 2004/058723), (3.13) kresoxim-methyl (143390-89-0) (WO 2004/058723), (3.14) metominostrobin (133408-50-1 ) (WO 2004/058723), (3.15) orysastrobin (189892- 69-1 ) (WO 2004/058723), (3.16) picoxystrobin (1 17428-22-5) (WO 2004/058723), (3.17) pyraclostrobin (175013-18-0) (WO 2004/058723), (3.18) pyrametostrobin (915410-70-7) (WO 2004/058723), (3.19) pyraoxystrobin (862588-1 1-2) (WO 2004/058723), (3.20) pyribencarb (799247-52-2) (WO 2004/058723),
(3.21 ) triclopyricarb (902760-40-1 ), (3.22) trifloxystrobin (141517-21-7) (WO 2004/058723), (3.23) (2E)-2- (2-{[6-(3-chloro-2-methylphenoxy)-5-fluoropyrimidin-4-yl]oxy}phenyl)-2-(methoxyimino)-N- methylethanamide (WO 2004/058723), (3.24) (2E)-2-(methoxyimino)-N-methyl-2-(2-{[({(1 E)-1-[3- (trifluoromethyl)phenyl]ethylidene}amino)oxy]methyl}phenyl)ethanamide (WO 2004/058723), (3.25) (2E)- 2-(methoxyimino)-N-methyl-2-{2-[(E)-({1-[3- (trifluoromethyl)phenyl]ethoxy}imino)methyl]phenyl}ethanamide (158169-73-4), (3.26) (2E)-2-{2-[({[(1 E)-1- (3-{[(E)-1-fluoro-2-phenylethenyl]oxy}phenyl)ethylidene]am
methylethanamide (326896-28-0), (3.27) (2E)-2-{2-[({[(2E,3E)-4-(2,6-dichlorophenyl)but-3-en-2- ylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylethanamide, (3.28) 2-chloro-N-(1 , 1 ,3- trimethyl-2,3-dihydro-1 H-inden-4-yl)pyridine-3-carboxamide (1 19899-14-8), (3.29) 5-methoxy-2-methyl-4- (2-{[({(1 E)-1-[3-(trifluoromethyl)phenyl]ethy^
3-one, (3.30) methyl (2E)-2-{2-[({cyclopropyl[(4-methoxyphenyl)imino]methyl}sulfanyl)m
methoxyprop-2-enoate (149601-03-6), (3.31 ) N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-(formylamino)-2- hydroxybenzamide (226551-21-9), (3.32) 2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N- methylacetamide (173662-97-0) and (3.33) (2R)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N- methylacetamide (394657-24-0).
(4) Inhibitors of the mitosis and cell division, for example (4.1 ) benomyl (17804-35-2), (4.2) carbendazim (10605-21-7), (4.3) chlorfenazole (3574-96-7), (4.4) diethofencarb (87130-20-9), (4.5) ethaboxam (162650-77-3), (4.6) fluopicolide (2391 10-15-7), (4.7) fuberidazole (3878-19-1 ), (4.8) pencycuron (66063-
05- 6), (4.9) thiabendazole (148-79-8), (4.10) thiophanate-m ethyl (23564-05-8), (4.1 1 ) thiophanate (23564-06-9), (4.12) zoxamide (156052-68-5), (4.13) 5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6- trifluorophenyl)[1 ,2,4]triazolo[1 ,5-a]pyrimidine (214706-53-3) and (4.14) 3-chloro-5-(6-chloropyridin-3-yl)-
6- methyl-4-(2,4,6-trifluorophenyl)pyridazine (1002756-87-7).
(5) Compounds capable to have a multisite action, like for example (5.1 ) bordeaux mixture (801 1-63-0), (5.2) captafol (2425-06-1 ), (5.3) captan (133-06-2) (WO 02/12172), (5.4) chlorothalonil (1897-45-6), (5.5) copper hydroxide (20427-59-2), (5.6) copper naphthenate (1338-02-9), (5.7) copper oxide (1317-39-1 ), (5.8) copper oxychloride (1332-40-7), (5.9) copper(2+) sulfate (7758-98-7), (5.10) dichlofluanid (1085-98- 9), (5.1 1 ) dithianon (3347-22-6), (5.12) dodine (2439-10-3), (5.13) dodine free base, (5.14) ferbam (14484-64-1 ), (5.15) fluorofolpet (719-96-0), (5.16) folpet (133-07-3), (5.17) guazatine (108173-90-6), (5.18) guazatine acetate, (5.19) iminoctadine (13516-27-3), (5.20) iminoctadine albesilate (169202-06-6), (5.21 ) iminoctadine triacetate (57520-17-9), (5.22) mancopper (53988-93-5), (5.23) mancozeb (8018-01- 7), (5.24) maneb (12427-38-2), (5.25) metiram (9006-42-2), (5.26) metiram zinc (9006-42-2), (5.27) oxine-copper (10380-28-6), (5.28) propamidine (104-32-5), (5.29) propineb (12071-83-9), (5.30) sulphur and sulphur preparations including calcium polysulphide (7704-34-9), (5.31 ) thiram (137-26-8), (5.32) tolylfluanid (731-27-1 ), (5.33) zineb (12122-67-7) and (5.34) ziram (137-30-4).
(6) Compounds capable to induce a host defence, like for example (6.1 ) acibenzolar-S-methyl (135158- 54-2), (6.2) isotianil (224049-04-1 ), (6.3) probenazole (27605-76-1 ) and (6.4) tiadinil (223580-51-6).
(7) Inhibitors of the amino acid and/or protein biosynthesis, for example (7.1 ) andoprim (23951-85-1 ), (7.2) blasticidin-S (2079-00-7), (7.3) cyprodinil (121552-61-2), (7.4) kasugamycin (6980-18-3), (7.5) kasugamycin hydrochloride hydrate (19408-46-9), (7.6) mepanipyrim (1 10235-47-7), (7.7) pyrimethanil (531 12-28-0) and (7.8) 3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinoline (861647-32-7) (WO2005070917). (8) Inhibitors of the ATP production, for example (8.1 ) fentin acetate (900-95-8), (8.2) fentin chloride (639- 58-7), (8.3) fentin hydroxide (76-87-9) and (8.4) silthiofam (175217-20-6).
(9) Inhibitors of the cell wall synthesis, for example (9.1 ) benthiavalicarb (177406-68-7), (9.2)
dimethomorph (1 10488-70-5), (9.3) flumorph (21 1867-47-9), (9.4) iprovalicarb (140923-17-7), (9.5) mandipropamid (374726-62-2), (9.6) polyoxins (1 1 1 13-80-7), (9.7) polyoxorim (22976-86-9), (9.8) validamycin A (37248-47-8) and (9.9) valifenalate (283159-94-4; 283159-90-0).
(10) Inhibitors of the lipid and membrane synthesis, for example (10.1 ) biphenyl (92-52-4), (10.2) chloroneb (2675-77-6), (10.3) dicloran (99-30-9), (10.4) edifenphos (17109-49-8), (10.5) etridiazole (2593-15-9), (10.6) iodocarb (55406-53-6), (10.7) iprobenfos (26087-47-8), (10.8) isoprothiolane (50512- 35-1 ), (10.9) propamocarb (25606-41-1 ), (10.10) propamocarb hydrochloride (25606-41-1 ), (10.1 1 ) prothiocarb (19622-08-3), (10.12) pyrazophos (13457-18-6), (10.13) quintozene (82-68-8), (10.14) tecnazene (1 17-18-0) and (10.15) tolclofos-methyl (57018-04-9).
(1 1 ) Inhibitors of the melanine biosynthesis, for example (1 1.1 ) carpropamid (104030-54-8), (1 1.2) diclocymet (139920-32-4), (1 1.3) fenoxanil (1 15852-48-7), (1 1 .4) phthalide (27355-22-2), (1 1.5) pyroquilon (57369-32-1 ), (1 1 .6) tricyclazole (41814-78-2) and (1 1.7) 2,2,2-trifluoroethyl {3-methyl-1-[(4- methylbenzoyl)amino]butan-2-yl}carbamate (851524-22-6) (WO2005042474).
(12) Inhibitors of the nucleic acid synthesis, for example (12.1 ) benalaxyl (71626-1 1-4), (12.2) benalaxyl- M (kiralaxyl) (98243-83-5), (12.3) bupirimate (41483-43-6), (12.4) clozylacon (67932-85-8), (12.5) dimethirimol (5221-53-4), (12.6) ethirimol (23947-60-6), (12.7) furalaxyl (57646-30-7), (12.8) hymexazol (10004-44-1 ), (12.9) metalaxyl (57837-19-1 ), (12.10) metalaxyl-M (mefenoxam) (70630-17-0), (12.1 1 ) ofurace (58810-48-3), (12.12) oxadixyl (77732-09-3) and (12.13) oxolinic acid (14698-29-4).
(13) Inhibitors of the signal transduction, for example (13.1 ) chlozolinate (84332-86-5), (13.2) fenpiclonil (74738-17-3), (13.3) fludioxonil (131341-86-1 ), (13.4) iprodione (36734-19-7), (13.5) procymidone (32809-16-8), (13.6) quinoxyfen (124495-18-7) and (13.7) vinclozolin (50471-44-8).
(14) Compounds capable to act as an uncoupler, like for example (14.1 ) binapacryl (485-31-4), (14.2) dinocap (131-72-6), (14.3) ferimzone (89269-64-7), (14.4) fluazinam (79622-59-6) and (14.5)
meptyldinocap (131-72-6).
(15) Further compounds, like for example (15.1 ) benthiazole (21564-17-0), (15.2) bethoxazin (163269-30- 5), (15.3) capsimycin (70694-08-5), (15.4) carvone (99-49-0), (15.5) chinomethionat (2439-01-2), (15.6) pyriofenone (chlazafenone) (688046-61-9), (15.7) cufraneb (1 1096-18-7), (15.8) cyflufenamid (180409- 60-3), (15.9) cymoxanil (57966-95-7), (15.10) cyprosulfamide (221667-31-8), (15.1 1 ) dazomet (533-74-4), (15.12) debacarb (62732-91-6), (15.13) dichlorophen (97-23-4), (15.14) diclomezine (62865-36-5), (15.15) difenzoquat (49866-87-7), (15.16) difenzoquat methylsulphate (43222-48-6), (15.17)
diphenylamine (122-39-4), (15.18) ecomate, (15.19) fenpyrazamine (473798-59-3), (15.20) flumetover (154025-04-4), (15.21 ) fluoroimide (41205-21-4), (15.22) flusulfamide (106917-52-6), (15.23) flutianil (304900-25-2), (15.24) fosetyl-aluminium (39148-24-8), (15.25) fosetyl-calcium, (15.26) fosetyl-sodium (39148-16-8), (15.27) hexachlorobenzene (1 18-74-1 ), (15.28) irumamycin (81604-73-1 ), (15.29) methasulfocarb (66952-49-6), (15.30) methyl isothiocyanate (556-61-6), (15.31 ) metrafenone (220899- 03-6), (15.32) mildiomycin (67527-71-3), (15.33) natamycin (7681-93-8), (15.34) nickel
dimethyldithiocarbamate (15521-65-0), (15.35) nitrothal-isopropyl (10552-74-6), (15.36) octhilinone (26530-20-1 ), (15.37) oxamocarb (917242-12-7), (15.38) oxyfenthiin (34407-87-9), (15.39)
pentachlorophenol and salts (87-86-5), (15.40) phenothrin, (15.41 ) phosphorous acid and its salts (13598-36-2), (15.42) propamocarb-fosetylate, (15.43) propanosine-sodium (88498-02-6), (15.44) proquinazid (189278-12-4), (15.45) pyrimorph (868390-90-3), (15.46) pyrrolnitrine (1018-71-9) (EP-A 1 559 320), (15.47) tebufloquin (376645-78-2), (15.48) tecloftalam (76280-91-6), (15.49) tolnifanide (30491 1-98-6), (15.50) triazoxide (72459-58-6), (15.51 ) trichlamide (70193-21-4), (15.52) zarilamid (84527-51-5), (15.53) (3S,6S,7R,8R)-8-benzyl-3-[({3-[(isobutyryloxy)methoxy]-4-methoxypyridin-2- yl}carbonyl)amino]-6-methyl-4,9-dioxo-1 ,5-dioxonan-7-yl 2-methylpropanoate (517875-34-2)
(WO2003035617), (15.54) 1-(4-{4-[(5R)-5-(2,6-difluorophenyl)-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3-thiazol-2- yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]ethanone (1003319-79-6) (WO
2008013622), (15.55) 1-(4-{4-[(5S)-5-(2,6-difluorophenyl)-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3-thiazol-2- yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]ethanone (1003319-80-9) (WO
2008013622), (15.56) 1-(4-{4-[5-(2,6-difluorophenyl)-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3-thiazol-2- yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]ethanone (1003318-67-9) (WO
2008013622), (15.57) 1-(4-methoxyphenoxy)-3,3-dimethylbutan-2-yl 1 H-imidazole-1-carboxylate
(1 1 1227-17-9), (15.58) 2,3,5,6-tetrachloro-4-(methylsulfonyl)pyridine (13108-52-6), (15.59) 2,3-dibutyl-6- chlorothieno[2,3-d]pyrimidin-4(3H)-one (221451-58-7), (15.60) 2,6-dimethyl-1 H,5H-[1 ,4]dithiino[2,3-c:5,6- c']dipyrrole-1 ,3,5,7(2H,6H)-tetrone, (15.61 ) 2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]-1-(4-{4-[(5R)- 5-phenyl-4,5-dihydro-1 ,2-oxazol-3-yl]-1 ,3-thiazol-2-yl}piperidin-1 -yl)ethanone (1003316-53-7) (WO 2008013622), (15.62) 2-[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]-1-(4-{4-[(5S)-5-phenyl-4, 5-dihydro- 1 ,2-oxazol-3-yl]-1 ,3-thiazol-2-yl}piperidin-1-yl)ethanone (1003316-54-8) (WO 2008013622), (15.63) 2-[5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl]-1-{4-[4-(5-phenyl-4,5-dihydro-1 ,2-oxazol-3-yl)-1 ^
yl]piperidin-1-yl}ethanone (1003316-51-5) (WO 2008013622), (15.64) 2-butoxy-6-iodo-3-propyl-4H- chromen-4-one, (15.65) 2-chloro-5-[2-chloro-1-(2,6-difluoro-4-methoxyphenyl)-4-methyl-1 H-imidazol-5- yl]pyridine, (15.66) 2-phenylphenol and salts (90-43-7), (15.67) 3-(4,4,5-trifluoro-3,3-dimethyl-3,4- dihydroisoquinolin-1-yl)quinoline (861647-85-0) (WO2005070917), (15.68) 3,4,5-trichloropyridine-2,6- dicarbonitrile (17824-85-0), (15.69) 3-[5-(4-chlorophenyl)-2,3-dimethyl-1 ,2-oxazolidin-3-yl]pyridine, (15.70) 3-chloro-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-6-methylpyridazine, (15.71 ) 4-(4-chlorophenyl)-5-(2,6- difluorophenyl)-3,6-dimethylpyridazine, (15.72) 5-amino-1 ,3,4-thiadiazole-2-thiol, (15.73) 5-chloro-N'- phenyl-N'-(prop-2-yn-1-yl)thiophene-2-sulfonohydrazide (134-31-6), (15.74) 5-fluoro-2-[(4- fluorobenzyl)oxy]pyrimidin-4-amine (1 174376-1 1-4) (WO2009094442), (15.75) 5-fluoro-2-[(4- methylbenzyl)oxy]pyrimidin-4-amine (1 174376-25-0) (WO2009094442), (15.76) 5-methyl-6- octyl[1 ,2,4]triazolo[1 ,5-a]pyrimidin-7-amine, (15.77) ethyl (2Z)-3-amino-2-cyano-3-phenylprop-2-enoate, (15.78) N'-(4-{[3-(4-chlorobenzyl)-1 ,2,4-thiadiazol-5-yl]oxy}-2,5-dimethylphenyl)-N-ethyl-N- methylimidoformamide, (15.79) N-(4-chlorobenzyl)-3-[3-methoxy-4-(prop-2-yn-1- yloxy)phenyl]propanamide, (15.80) N-[(4-chlorophenyl)(cyano)methyl]-3-[3-methoxy-4-(prop-2-yn-1- yloxy)phenyl]propanamide, (15.81 ) N-[(5-bromo-3-chloropyridin-2-yl)methyl]-2,4-dichloropyridine-3- carboxamide, (15.82) N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2,4-dichloropyridine-3-carboxamid^ (15.83) N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2-fluoro-4-iodopyridine-3-carboxamide, (15.84) N-{(E)- [(cyclopropylmethoxy)imino][6-(difluoromethoxy)-2,3-difluorophenyl]methy^ (221201- 92-9), (15.85) N-{(Z)-[(cyclopropylmethoxy)imino][6-(difluoromethoxy)-2,3-difluorophenyl]m
phenylacetamide (221201-92-9), (15.86) N'-{4-[(3-tert-butyl-4-cyano-1 ,2-thiazol-5-yl)oxy]-2-chloro-5- methylphenyl}-N-ethyl-N-methylimidoformamide, (15.87) N-methyl-2-(1-{[5-methyl-3-(trifluoromethyl)-1 H- pyrazol-1-yl]acetyl}piperidin-4-yl)-N-(1 ,2,3,4-tetrahydro^
(922514-49-6) (WO 2007014290), (15.88) N-methyl-2-(1-{[5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1- yl]acetyl}piperidin-4-yl)-N-[(1 R)-1 ,2,3,4-tetrahydronaphthalen-1-yl]-1 ,3-thiazole-4-carboxamide (922514- 07-6) (WO 2007014290), (15.89) N-methyl-2-(1-{[5-methyl-3-(trifluorom
yl]acetyl}piperidin-4-yl)-N-[(1 S)-1 ,2,3,4-tetrahydro^ (922514- 48-5) (WO 2007014290), (15.90) pentyl {6-[({[(1-methyl-1 H-tetrazol-5- yl)(phenyl)methylidene]amino}oxy)methyl]pyridin-2-yl}carbamate, (15.91 ) phenazine-1-carboxylic acid, (15.92) quinolin-8-ol (134-31-6), (15.93) quinolin-8-ol sulfate (2: 1 ) (134-31-6) and (15.94) tert-butyl {6- [({[(1-methyl-1 H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}carba
(16) Further compounds, like for example (16.1 ) 1-methyl-3-(trifluoromethyl)-N-[2'- (trifluoromethyl)biphenyl-2-yl]-1 H-pyrazole-4-carboxamide, (16.2) N-(4'-chlorobiphenyl-2-yl)-3- (difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide, (16.3) N-(2',4'-dichlorobiphenyl-2-yl)-3- (difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide, (16.4) 3-(difluoromethyl)-1-methyl-N-[4'- (trifluoromethyl)biphenyl-2-yl]-1 H-pyrazole-4-carboxamide, (16.5) N-(2',5'-difluorobiphenyl-2-yl)-1-methyl- 3-(trifluoromethyl)-1 H-pyrazole-4-carboxamide, (16.6) 3-(difluoromethyl)-1-methyl-N-[4'-(prop-1-yn-1- yl)biphenyl-2-yl]-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.7) 5-fluoro-1 ,3- dimethyl-N-[4'-(prop-1-yn-1-yl)biphenyl-2-yl]-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.8) 2-chloro-N-[4'-(prop-1-yn-1-yl)biphenyl-2-yl]pyridine-3-carboxamide (known from WO
2004/058723), (16.9) 3-(difluoromethyl)-N-[4'-(3,3-dimethylbut-1-yn-1-yl)biphenyl-2-yl]-1-methyl-1 H- pyrazole-4-carboxamide (known from WO 2004/058723), (16.10) N-[4'-(3,3-dimethylbut-1-yn-1- yl)biphenyl-2-yl]-5-fluoro-1 ,3-dimethyl-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.1 1 ) 3-(difluoromethyl)-N-(4'-ethynylbiphenyl-2-yl)-1-methyl-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.12) N-(4'-ethynylbiphenyl-2-yl)-5-fluoro-1 ,3-dimethyl-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.13) 2-chloro-N-(4'-ethynylbiphenyl-2-yl)pyridine-3-carboxamide (known from WO 2004/058723), (16.14) 2-chloro-N-[4'-(3,3-dimethylbut-1-yn-1-yl)biphenyl-2-yl]pyridine-3- carboxamide (known from WO 2004/058723), (16.15) 4-(difluoromethyl)-2-methyl-N-[4'- (trifluoromethyl)biphenyl-2-yl]-1 ,3-thiazole-5-carboxamide (known from WO 2004/058723), (16.16) 5- fluoro-N-[4'-(3-hydroxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]-1 ,3-dimethyl-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.17) 2-chloro-N-[4'-(3-hydroxy-3-methylbut-1-yn-1-yl)biphenyl-2- yl]pyridine-3-carboxamide (known from WO 2004/058723), (16.18) 3-(difluoromethyl)-N-[4'-(3-methoxy-3- methylbut-1-yn-1-yl)biphenyl-2-yl]-1-methyl-1 H-pyrazole-4-carboxamide (known from WO 2004/058723), (16.19) 5-fluoro-N-[4'-(3-methoxy-3-methylbut-1-yn-1-yl)biphenyl-2-yl]-1 ,3-dimethyl-1 H-pyrazole-4- carboxamide (known from WO 2004/058723), (16.20) 2-chloro-N-[4'-(3-methoxy-3-methylbut-1-yn-1- yl)biphenyl-2-yl]pyridine-3-carboxamide (known from WO 2004/058723), (16.21 ) (5-bromo-2-methoxy-4- methylpyridin-3-yl)(2,3,4-trimethoxy-6-methylphenyl)methanone (known from EP-A 1 559 320) and (16.22) N-[2-(4-{[3-(4-chlorophenyl)prop-2-yn-1-yl]oxy}-3-methoxyphenyl)ethyl]-N2- (methylsulfonyl)valinamide (220706-93-4).
All named mixing partners of the classes (1 ) to (16) can, if their functional groups enable this, optionally form salts with suitable bases or acids.
The composition according to the invention comprising a mixture of a compound of formula (I) with a bactericide compound can also be particularly advantageous. Examples of suitable bactericide mixing partners can be selected in the following list: bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracycline, probenazole, streptomycin, tecloftalam, copper sulphate and other copper preparations.
The compounds of formula (I) and the fungicide composition according to the invention can be used to curatively or preventively control the phytopathogenic fungi of plants or crops.
Thus, according to a further aspect of the invention, there is provided a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops characterised in that a compound of formula (I) or a fungicide composition according to the invention is applied to the seed, the plant or to the fruit of the plant or to the soil wherein the plant is growing or wherein it is desired to grow.
The method of treatment according to the invention can also be useful to treat propagation material such as tubers or rhizomes, but also seeds, seedlings or seedlings pricking out and plants or plants pricking out. This method of treatment can also be useful to treat roots. The method of treatment according to the invention can also be useful to treat the overground parts of the plant such as trunks, stems or stalks, leaves, flowers and fruit of the concerned plant.
According to the invention all plants and plant parts can be treated. By plants is meant all plants and plant populations such as desirable and undesirable wild plants, cultivars and plant varieties (whether or not protectable by plant variety or plant breeder's rights). Cultivars and plant varieties can be plants obtained by conventional propagation and breeding methods which can be assisted or supplemented by one or more biotechnological methods such as by use of double haploids, protoplast fusion, random and directed mutagenesis, molecular or genetic markers or by bioengineering and genetic engineering methods. By plant parts is meant all above ground and below ground parts and organs of plants such as shoot, leaf, blossom and root, whereby for example leaves, needles, stems, branches, blossoms, fruiting bodies, fruits and seed as well as roots, corms and rhizomes are listed. Crops and vegetative and generative propagating material, for example cuttings, corms, rhizomes, runners and seeds also belong to plant parts.
Among the plants that can be protected by the method according to the invention, mention may be made of major field crops like corn, soybean, cotton, Brassica oilseeds such as Brassica napus (e.g. canola), Brassica rapa, B. juncea (e.g. mustard) and Brassica carinata, rice, wheat, sugarbeet, sugarcane, oats, rye, barley, millet, triticale, flax, vine and various fruits and vegetables of various botanical taxa such as Rosaceae sp. (for instance pip fruit such as apples and pears, but also stone fruit such as apricots, cherries, almonds and peaches, berry fruits such as strawberries), Ribesioidae sp., Juglandaceae sp., Betulaceae sp.,
Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp. (for instance banana trees and plantings), Rubiaceae sp. (for instance coffee), Theaceae sp., Sterculiceae sp., Rutaceae sp. (for instance lemons, oranges and grapefruit) ; Solanaceae sp. (for instance tomatoes, potatoes, peppers, eggplant), Liliaceae sp., Compositiae sp. (for instance lettuce, artichoke and chicory - including root chicory, endive or common chicory), Umbelliferae sp. (for instance carrot, parsley, celery and celeriac), Cucurbitaceae sp. (for instance cucumber - including pickling cucumber, squash, watermelon, gourds and melons), Alliaceae sp. (for instance onions and leek), Cruciferae sp. (for instance white cabbage, red cabbage, broccoli, cauliflower, brussel sprouts, pak choi, kohlrabi, radish, horseradish, cress, Chinese cabbage), Leguminosae sp. (for instance peanuts, peas and beans beans - such as climbing beans and broad beans), Chenopodiaceae sp. (for instance mangold, spinach beet, spinach, beetroots), Malvaceae (for instance okra), Asparagaceae (for instance asparagus); horticultural and forest crops; ornamental plants; as well as genetically modified homologues of these crops.
The method of treatment according to the invention can be used in the treatment of genetically modified organisms (GMOs), e.g. plants or seeds. Genetically modified plants (or transgenic plants) are plants of which a heterologous gene has been stably integrated into genome. The expression "heterologous gene" essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which are present in the plant (using for example, antisense technology, cosuppression technology or RNA interference - RNAi - technology). A heterologous gene that is located in the genome is also called a transgene. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also result in superadditive ("synergistic") effects. Thus, for example, reduced application rates and/or a widening of the activity spectrum and/or an increase in the activity of the active compounds and compositions which can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, bigger fruits, larger plant height, greener leaf color, earlier flowering, higher quality and/or a higher nutritional value of the harvested products, higher sugar concentration within the fruits, better storage stability and/or processability of the harvested products are possible, which exceed the effects which were actually to be expected.
At certain application rates, the active compound combinations according to the invention may also have a strengthening effect in plants. Accordingly, they are also suitable for mobilizing the defense system of the plant against attack by unwanted microorganisms. This may, if appropriate, be one of the reasons of the enhanced activity of the combinations according to the invention, for example against fungi. Plant- strengthening (resistance-inducing) substances are to be understood as meaning, in the present context, those substances or combinations of substances which are capable of stimulating the defense system of plants in such a way that, when subsequently inoculated with unwanted microorganisms, the treated plants display a substantial degree of resistance to these microorganisms. In the present case, unwanted microorganisms are to be understood as meaning phytopathogenic fungi, bacteria and viruses. Thus, the substances according to the invention can be employed for protecting plants against attack by the abovementioned pathogens within a certain period of time after the treatment. The period of time within which protection is effected generally extends from 1 to 10 days, preferably 1 to 7 days, after the treatment of the plants with the active compounds. Plants and plant cultivars which are preferably to be treated according to the invention include all plants which have genetic material which impart particularly advantageous, useful traits to these plants (whether obtained by breeding and/or biotechnological means).
Plants and plant cultivars which are also preferably to be treated according to the invention are resistant against one or more biotic stresses, i.e. said plants show a better defense against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.
Examples of nematode resistant plants are described in e.g. US Patent Application Nos 1 1/765,491 , 1 1/765,494, 10/926,819, 10/782,020, 12/032,479, 10/783,417, 10/782,096, 1 1/657,964, 12/192,904, 1 1/396,808, 12/166,253, 12/166,239, 12/166,124, 12/166,209, 1 1/762,886, 12/364,335, 1 1/763,947, 12/252,453, 12/209,354, 12/491 ,396 or 12/497,221.
Plants and plant cultivars which may also be treated according to the invention are those plants which are resistant to one or more abiotic stresses. Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients, shade avoidance.
Plants and plant cultivars which may also be treated according to the invention, are those plants characterized by enhanced yield characteristics. Increased yield in said plants can be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation. Yield can furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance. Further yield traits include seed composition, such as carbohydrate content, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
Examples of plants with the above-mentioned traits are non-exhaustively listed in Table A. Plants that may be treated according to the invention are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses). Such plants are typically made by crossing an inbred male-sterile parent line (the female parent) with another inbred male-fertile parent line (the male parent). Hybrid seed is typically harvested from the male sterile plants and sold to growers. Male sterile plants can sometimes (e.g. in corn) be produced by detasseling, i.e. the mechanical removal of the male reproductive organs (or males flowers) but, more typically, male sterility is the result of genetic determinants in the plant genome. In that case, and especially when seed is the desired product to be harvested from the hybrid plants it is typically useful to ensure that male fertility in the hybrid plants is fully restored. This can be accomplished by ensuring that the male parents have appropriate fertility restorer genes which are capable of restoring the male fertility in hybrid plants that contain the genetic determinants responsible for male-sterility. Genetic determinants for male sterility may be located in the cytoplasm. Examples of cytoplasmic male sterility (CMS) were for instance described in Brassica species (WO 92/05251 , WO 95/09910, WO 98/27806, WO 05/002324, WO 06/021972 and US 6,229,072).
However, genetic determinants for male sterility can also be located in the nuclear genome. Male sterile plants can also be obtained by plant biotechnology methods such as genetic engineering. A particularly useful means of obtaining male-sterile plants is described in WO 89/10396 in which, for example, a ribonuclease such as barnase is selectively expressed in the tapetum cells in the stamens. Fertility can then be restored by expression in the tapetum cells of a ribonuclease inhibitor such as barstar (e.g. WO 91/02069). Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated according to the invention are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance.
Herbicide-resistant plants are for example glyphosate-tolerant plants, i.e. plants made tolerant to the herbicide glyphosate or salts thereof. Plants can be made tolerant to glyphosate through different means. For example, glyphosate-tolerant plants can be obtained by transforming the plant with a gene encoding the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Examples of such EPSPS genes are the AroA gene (mutant CT7) of the bacterium Salmonella typhimurium (Comai et al., 1983, Science 221 , 370-371 ), the CP4 gene of the bacterium Agrobacterium sp. (Barry et al., 1992, Curr. Topics Plant Physiol. 7, 139-145), the genes encoding a Petunia EPSPS (Shah et al., 1986, Science 233, 478-481 ), a Tomato EPSPS (Gasser et al., 1988, J. Biol. Chem. 263, 4280-4289), or an Eleusine EPSPS (WO 01/66704). It can also be a mutated EPSPS as described in for example EP 0837944, WO 00/66746, WO 00/66747 or WO02/26995. Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate oxido-reductase enzyme as described in U.S. Patent Nos. 5,776,760 and 5,463, 175. Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate acetyl transferase enzyme as described in for example WO 02/36782, WO 03/092360, WO 05/012515 and WO 07/024782. Glyphosate-tolerant plants can also be obtained by selecting plants containing naturally-occurring mutations of the above-mentioned genes, as described in for example WO 01/024615 or WO 03/013226. Plants expressing EPSPS genes that confer glyphosate tolerance are described in e.g. US Patent Application Nos 1 1/517,991 , 10/739,610, 12/139,408, 12/352,532,
1 1/312,866, 1 1/315,678, 12/421 ,292, 1 1/400,598, 1 1/651 ,752, 1 1/681 ,285, 1 1/605,824, 12/468,205, 1 1/760,570, 1 1/762,526, 1 1/769,327, 1 1/769,255, 1 1/943801 or 12/362,774. Plants comprising other genes that confer glyphosate tolerance, such as decarboxylase genes, are described in e.g. US patent applications 1 1/588,81 1 , 1 1/185,342, 12/364,724, 1 1/185,560 or 12/423,926.
Other herbicide resistant plants are for example plants that are made tolerant to herbicides inhibiting the enzyme glutamine synthase, such as bialaphos, phosphinothricin or glufosinate. Such plants can be obtained by expressing an enzyme detoxifying the herbicide or a mutant glutamine synthase enzyme that is resistant to inhibition, e.g. described in US Patent Application No 1 1/760,602. One such efficient detoxifying enzyme is an enzyme encoding a phosphinothricin acetyltransferase (such as the bar or pat protein from Streptomyces species). Plants expressing an exogenous phosphinothricin acetyltransferase are for example described in U.S. Patent Nos. 5,561 ,236; 5,648,477; 5,646,024; 5,273,894; 5,637,489; 5,276,268; 5,739,082; 5,908,810 and 7, 1 12,665.
Further herbicide-tolerant plants are also plants that are made tolerant to the herbicides inhibiting the enzyme hydroxyphenylpyruvatedioxygenase (HPPD). Hydroxyphenylpyruvatedioxygenases are enzymes that catalyze the reaction in which para-hydroxyphenylpyruvate (HPP) is transformed into homogentisate. Plants tolerant to HPPD-inhibitors can be transformed with a gene encoding a naturally-occurring resistant HPPD enzyme, or a gene encoding a mutated or chimeric HPPD enzyme as described in WO 96/38567, WO 99/24585, WO 99/24586, WO 2009/144079, WO 2002/046387, or US 6,768,044..
Tolerance to HPPD-inhibitors can also be obtained by transforming plants with genes encoding certain enzymes enabling the formation of homogentisate despite the inhibition of the native HPPD enzyme by the HPPD-inhibitor. Such plants and genes are described in WO 99/34008 and WO 02/36787. Tolerance of plants to HPPD inhibitors can also be improved by transforming plants with a gene encoding an enzyme having prephenate deshydrogenase (PDH) activity in addition to a gene encoding an HPPD- tolerant enzyme, as described in WO 2004/024928. Further, plants can be made more tolerant to HPPD- inhibitor herbicides by adding into their genome a gene encoding an enzyme capable of metabolizing or degrading HPPD inhibitors, such as the CYP450 enzymes shown in WO 2007/103567 and WO
2008/150473.
Still further herbicide resistant plants are plants that are made tolerant to acetolactate synthase (ALS) inhibitors. Known ALS-inhibitors include, for example, sulfonylurea, imidazolinone, triazolopyrimidines, pryimidinyoxy(thio)benzoates, and/or sulfonylaminocarbonyltriazolinone herbicides. Different mutations in the ALS enzyme (also known as acetohydroxyacid synthase, AHAS) are known to confer tolerance to different herbicides and groups of herbicides, as described for example in Tranel and Wright (2002, Weed Science 50:700-712), but also, in U.S. Patent No. 5,605,01 1 , 5,378,824, 5, 141 ,870, and 5,013,659. The production of sulfonylurea-tolerant plants and imidazolinone-tolerant plants is described in U.S. Patent Nos. 5,605,01 1 ; 5,013,659; 5,141 ,870; 5,767,361 ; 5,731 ,180; 5,304,732; 4,761 ,373; 5,331 , 107;
5,928,937; and 5,378,824; and international publication WO 96/33270. Other imidazolinone-tolerant plants are also described in for example WO 2004/040012, WO 2004/106529, WO 2005/020673, WO 2005/093093, WO 2006/007373, WO 2006/015376, WO 2006/024351 , and WO 2006/060634. Further sulfonylurea- and imidazolinone-tolerant plants are also described in for example WO 07/024782 and US Patent Application No 61/288958.
Other plants tolerant to imidazolinone and/or sulfonylurea can be obtained by induced mutagenesis, selection in cell cultures in the presence of the herbicide or mutation breeding as described for example for soybeans in U.S. Patent 5,084,082, for rice in WO 97/41218, for sugar beet in U.S. Patent 5,773,702 and WO 99/057965, for lettuce in U.S. Patent 5,198,599, or for sunflower in WO 01/065922. Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are insect-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.
An "insect-resistant transgenic plant", as used herein, includes any plant containing at least one transgene comprising a coding sequence encoding:
1 ) an insecticidal crystal protein from Bacillus thuringiensis or an insecticidal portion thereof, such as the insecticidal crystal proteins listed by Crickmore et al. (1998, Microbiology and Molecular Biology Reviews, 62: 807-813), updated by Crickmore et al. (2005) at the Bacillus thuringiensis toxin nomenclature, online at:
http://www.lifesci.sussex.ac.uk Home/Neil_Crickmore/Bt ), or insecticidal portions thereof, e.g., proteins of the Cry protein classes CrylAb, CrylAc, Cryl B, Cryl C, Cryl D, Cryl F, Cry2Ab, Cry3Aa, or Cry3Bb or insecticidal portions thereof (e.g. EP 1999141 and WO 2007/107302), or such proteins encoded by synthetic genes as e.g. described in and US Patent Application No 12/249,016 ; or
2) a crystal protein from Bacillus thuringiensis or a portion thereof which is insecticidal in the presence of a second other crystal protein from Bacillus thuringiensis or a portion thereof, such as the binary toxin made up of the Cry34 and Cry35 crystal proteins (Moellenbeck et al. 2001 , Nat. Biotechnol. 19: 668-72; Schnepf et al. 2006, Applied Environm. Microbiol. 71 , 1765-1774) or the binary toxin made up of the CrylA or Cryl F proteins and the Cry2Aa or Cry2Ab or Cry2Ae proteins (US Patent Appl. No. 12/214,022 and EP 08010791.5); or
3) a hybrid insecticidal protein comprising parts of different insecticidal crystal proteins from Bacillus thuringiensis, such as a hybrid of the proteins of 1 ) above or a hybrid of the proteins of 2) above, e.g., the Cry1A.105 protein produced by corn event MON89034 (WO 2007/027777); or
4) a protein of any one of 1 ) to 3) above wherein some, particularly 1 to 10, amino acids have been replaced by another amino acid to obtain a higher insecticidal activity to a target insect species, and/or to expand the range of target insect species affected, and/or because of changes introduced into the encoding DNA during cloning or transformation, such as the Cry3Bb1 protein in corn events MON863 or MON88017, or the Cry3A protein in corn event MIR604; or
5) an insecticidal secreted protein from Bacillus thuringiensis or Bacillus cereus, or an insecticidal portion thereof, such as the vegetative insecticidal (VIP) proteins listed at:
http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/vip.html, e.g., proteins from the VIP3Aa protein class; or
6) a secreted protein from Bacillus thuringiensis or Bacillus cereus which is insecticidal in the presence of a second secreted protein from Bacillus thuringiensis or B. cereus, such as the binary toxin made up of the VIPIA and VIP2A proteins (WO 94/21795); or
7) a hybrid insecticidal protein comprising parts from different secreted proteins from Bacillus thuringiensis or Bacillus cereus, such as a hybrid of the proteins in 1 ) above or a hybrid of the proteins in 2) above; or
8) a protein of any one of 5) to 7) above wherein some, particularly 1 to 10, amino acids have been replaced by another amino acid to obtain a higher insecticidal activity to a target insect species, and/or to expand the range of target insect species affected, and/or because of changes introduced into the encoding DNA during cloning or transformation (while still encoding an insecticidal protein), such as the VIP3Aa protein in cotton event COT102; or 9) a secreted protein from Bacillus thuringiensis or Bacillus cereus which is insecticidal in the presence of a crystal protein from Bacillus thuringiensis, such as the binary toxin made up of VIP3 and CrylA or Cryl F (US Patent Appl. No. 61/126083 and 61/195019), or the binary toxin made up of the VIP3 protein and the Cry2Aa or Cry2Ab or Cry2Ae proteins (US Patent Appl. No. 12/214,022 and EP 08010791.5).
10) a protein of 9) above wherein some, particularly 1 to 10, amino acids have been replaced by another amino acid to obtain a higher insecticidal activity to a target insect species, and/or to expand the range of target insect species affected, and/or because of changes introduced into the encoding DNA during cloning or transformation (while still encoding an insecticidal protein)
Of course, an insect-resistant transgenic plant, as used herein, also includes any plant comprising a combination of genes encoding the proteins of any one of the above classes 1 to 10. In one embodiment, an insect-resistant plant contains more than one transgene encoding a protein of any one of the above classes 1 to 10, to expand the range of target insect species affected when using different proteins directed at different target insect species, or to delay insect resistance development to the plants by using different proteins insecticidal to the same target insect species but having a different mode of action, such as binding to different receptor binding sites in the insect.
An "insect-resistant transgenic plant", as used herein, further includes any plant containing at least one transgene comprising a sequence producing upon expression a double-stranded RNA which upon ingestion by a plant insect pest inhibits the growth of this insect pest, as described e.g. in WO
2007/080126, WO 2006/129204, WO 2007/074405, WO 2007/080127 and WO 2007/035650.
Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance. Particularly useful stress tolerance plants include:
1 ) plants which contain a transgene capable of reducing the expression and/or the activity of poly(ADP-ribose) polymerase (PARP) gene in the plant cells or plants as described in WO 00/04173, WO/2006/045633, EP 04077984.5, or EP 06009836.5.
2) plants which contain a stress tolerance enhancing transgene capable of reducing the expression and/or the activity of the PARG encoding genes of the plants or plants cells, as described e.g. in WO 2004/090140.
3) plants which contain a stress tolerance enhancing transgene coding for a plant-functional enzyme of the nicotineamide adenine dinucleotide salvage synthesis pathway including nicotinamidase, nicotinate phosphoribosyltransferase, nicotinic acid mononucleotide adenyl transferase, nicotinamide adenine dinucleotide synthetase or nicotine amide
phosphorybosyltransferase as described e.g. in EP 04077624.7, WO 2006/133827,
PCT/EP07/002433, EP 1999263, or WO 2007/107326.
Plants or plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention show altered quantity, quality and/or storage-stability of the harvested product and/or altered properties of specific ingredients of the harvested product such as :
1 ) transgenic plants which synthesize a modified starch, which in its physical-chemical characteristics, in particular the amylose content or the amylose/amylopectin ratio, the degree of branching, the average chain length, the side chain distribution, the viscosity behaviour, the gelling strength, the starch grain size and/or the starch grain morphology, is changed in comparison with the synthesised starch in wild type plant cells or plants, so that this is better suited for special applications. Said transgenic plants synthesizing a modified starch are disclosed, for example, in EP 0571427, WO 95/04826, EP 0719338, WO 96/15248, WO
96/19581 , WO 96/27674, WO 97/1 1 188, WO 97/26362, WO 97/32985, WO 97/42328, WO 97/44472, WO 97/45545, WO 98/27212, WO 98/40503, W099/58688, WO 99/58690, WO 99/58654, WO 00/08184, WO 00/08185, WO 00/08175, WO 00/28052, WO 00/77229, WO 01/12782, WO 01/12826, WO 02/101059, WO 03/071860, WO 2004/056999, WO 2005/030942, WO 2005/030941 , WO 2005/095632, WO 2005/095617, WO 2005/095619, WO 2005/095618, WO 2005/123927, WO 2006/018319, WO 2006/103107, WO 2006/108702, WO 2007/009823, WO 00/22140, WO 2006/063862, WO 2006/072603, WO 02/034923, EP 06090134.5, EP 06090228.5, EP 06090227.7, EP 07090007.1 , EP 07090009.7, WO 01/14569, WO 02/79410, WO 03/33540, WO 2004/078983, WO 01/19975, WO 95/26407, WO 96/34968, WO 98/20145, WO 99/12950, WO 99/66050, WO 99/53072, US 6,734,341 , WO 00/1 1 192, WO 98/22604, WO 98/32326, WO 01/98509, WO 01/98509, WO 2005/002359, US 5,824,790, US 6,013,861 , WO 94/04693, WO 94/09144, WO 94/1 1520, WO 95/35026, WO 97/20936
2) transgenic plants which synthesize non starch carbohydrate polymers or which synthesize non starch carbohydrate polymers with altered properties in comparison to wild type plants without genetic modification. Examples are plants producing polyfructose, especially of the inulin and levan-type, as disclosed in EP 0663956, WO 96/01904, WO 96/21023, WO 98/39460, and WO 99/24593, plants producing alpha-1 ,4-glucans as disclosed in WO 95/31553, US 2002031826, US 6,284,479, US 5,712, 107, WO 97/47806, WO 97/47807, WO 97/47808 and WO 00/14249, plants producing alpha-1 ,6 branched alpha-1 ,4-glucans, as disclosed in WO 00/73422, plants producing alternan, as disclosed in e.g. WO 00/47727, WO 00/73422, EP 06077301.7, US 5,908,975 and EP 0728213,
3) transgenic plants which produce hyaluronan, as for example disclosed in WO 2006/032538, WO 2007/039314, WO 2007/039315, WO 2007/039316, JP 2006304779, and WO 2005/012529.
4) transgenic plants or hybrid plants, such as onions with characteristics such as 'high soluble solids content', 'low pungency' (LP) and/or 'long storage' (LS), as described in US Patent Appl. No. 12/020,360 and 61/054,026.
Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as cotton plants, with altered fiber characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered fiber characteristics and include:
a) Plants, such as cotton plants, containing an altered form of cellulose synthase genes as described in WO 98/00549
b) Plants, such as cotton plants, containing an altered form of rsw2 or rsw3 homologous nucleic acids as described in WO 2004/053219
c) Plants, such as cotton plants, with increased expression of sucrose phosphate synthase as described in WO 01/17333
d) Plants, such as cotton plants, with increased expression of sucrose synthase as described in WO 02/45485
e) Plants, such as cotton plants, wherein the timing of the plasmodesmatal gating at the basis of the fiber cell is altered, e.g. through downregulation of fiber-selective -1 ,3-glucanase as described in WO 2005/017157, or as described in EP 08075514.3 or US Patent Appl. No. 61/128,938
f) Plants, such as cotton plants, having fibers with altered reactivity, e.g. through the expression of N-acetylglucosaminetransferase gene including nodC and chitin synthase genes as described in WO 2006/136351
Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered oil profile
characteristics and include:
a) Plants, such as oilseed rape plants, producing oil having a high oleic acid content as described e.g. in US 5,969,169, US 5,840,946 or US 6,323,392 or US 6,063,947 b) Plants such as oilseed rape plants, producing oil having a low linolenic acid content as described in US 6,270,828, US 6,169,190, or US 5,965,755
c) Plant such as oilseed rape plants, producing oil having a low level of saturated fatty acids as described e.g. in US Patent No. 5,434,283 or US Patent Application No 12/668303
Plants or plant cultivars (that can be obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered seed shattering characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered seed shattering characteristics and include plants such as oilseed rape plants with delayed or reduced seed shattering as described in US Patent Appl. No. 61/135,230 WO09/068313 and WO10/006732.
Particularly useful transgenic plants which may be treated according to the invention are plants containing transformation events, or combination of transformation events, that are the subject of petitions for non- regulated status, in the United States of America, to the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA) whether such petitions are granted or are still pending. At any time this information is readily available from APHIS (4700 River Road Riverdale, MD 20737, USA), for instance on its internet site (URL http://www.aphis.usda.gov/brs/not_reg.html). On the filing date of this application the petitions for nonregulated status that were pending with APHIS or granted by APHIS were those listed in table B which contains the following information:
Petition : the identification number of the petition. Technical descriptions of the transformation events can be found in the individual petition documents which are obtainable from APHIS, for example on the APHIS website, by reference to this petition number. These descriptions are herein incorporated by reference.
Extension of Petition : reference to a previous petition for which an extension is requested. Institution : the name of the entity submitting the petition.
Regulated article : the plant species concerned.
Transgenic phenotype : the trait conferred to the plants by the transformation event.
Transformation event or line : the name of the event or events (sometimes also designated as lines or lines) for which nonregulated status is requested.
APHIS documents : various documents published by APHIS in relation to the Petition and which can be requested with APHIS.
Additional particularly useful plants containing single transformation events or combinations of transformation events are listed for example in the databases from various national or regional regulatory agencies (see for example http://gmoinfo.jrc.it/gmp_browse.aspx and http://www.agbios.com/dbase.php).
Further particularly transgenic plants include plants containing a transgene in an agronomically neutral or beneficial position as described in any of the patent publications listed in Table C.
Table A
Trait Reference
Water use efficiency WO 2000/073475
Nitrogen use efficiency WO 1995/00991 1 WO 2007/0761 15
WO 1997/030163 WO 2005/103270
WO 2007/092704 WO 2002/002776
Improved photosynthesis WO 2008/056915 WO 2004/101751
Nematode resistance WO 1995/020669 WO 2003/033651
WO 2001/051627 WO 1999/060141
WO 2008/139334 WO 1998/012335
WO 2008/095972 WO 1996/030517
WO 2006/085966 WO 1993/018170
Reduced pod dehiscence WO 2006/009649 WO 1997/013865
WO 2004/1 13542 WO 1996/030529
WO 1999/015680 WO 1994/023043
WO 1999/000502
Aphid resistance WO 2006/125065 WO 2008/067043
WO 1997/046080 WO 2004/072109
Sclerotinia resistance WO 2006/135717 WO 2005/000007
WO 2006/055851 WO 2002/099385
WO 2005/090578 WO 2002/061043
Botrytis resistance WO 2006/046861 WO 2002/085105
Bremia resistance US 20070022496 WO 2004/049786
WO 2000/063432
Erwinia resistance WO 2004/049786
Closterovirus resistance WO 2007/073167 WO 2002/022836
WO 2007/053015
Stress tolerance (including WO 2010/019838 WO2008/002480 drought tolerance)
WO 2009/0491 10 WO2005/033318
Tobamovirus resistance WO 2006/038794 Table B
Petitions of Nonregulated Status Granted or Pending by APHIS
as of March 31, 2010
NOTE: To obtain the most up-to-date list of Crops No Longer Regulated, please look at the Current Status of Petitions. This list is automatically updated and reflects all petitions received to date by APHIS, including petitions pending, withdrawn, or approved.
Abbreviations:
CMV-cucumber mosaic virus; CPB-colorado potato beetle; PLRV- potato leafroll virus; PRSV-papaya ringspot virus; PVY-potato virus Y; WMV2- watermelon mosaic virus 2 ZYMV-zucchini yellow mosaic virus
Figure imgf000036_0001
Figure imgf000037_0001
Figure imgf000038_0001
Figure imgf000039_0001
Figure imgf000040_0001
Table C
Plant species Event Trait Patent reference
Corn PV-ZMGT32 (NK603) Glyphosate tolerance US 2007-056056
Corn MIR604 Insect resistance (Cry3a055) EP 1 737 290
Corn LY038 High lysine content US 7, 157,281
Corn 3272 Self processing corn (alpha- US 2006-230473 amylase)
Corn PV-ZMIR13 Insect resistance (Cry3Bb) US 2006-095986
(MON863)
Corn DAS-59122-7 Insect resistance US 2006-070139
(Cry34Ab1/Cry35Ab1 )
Corn TC1507 Insect resistance (Cryl F) US 7,435,807
Corn MON810 Insect resistance (CrylAb) US 2004-180373
Corn VIP1034 Insect resistance WO 03/052073
Corn B16 Glufosinate resistance US 2003-126634
Corn GA21 Glyphosate resistance US 6,040,497
Corn GG25 Glyphosate resistance US 6,040,497
Corn GJ1 1 Glyphosate resistance US 6,040,497
Corn FI1 17 Glyphosate resistance US 6,040,497
Corn GAT-ZM 1 Glufosinate tolerance WO 01/51654
Corn MON87460 Drought tolerance WO 2009/1 1 1263
Corn DP-098140-6 Glyphosate tolerance / ALS WO 2008/1 12019 inhibitor tolerance
Wheat Event 1 Fusarium resistance CA 2561992
(trichothecene 3-0- acetyltransferase)
Sugar beet T227-1 Glyphosate tolerance US 2004-1 17870
Sugar beet H7-1 Glyphosate tolerance WO 2004-074492
Soybean MON89788 Glyphosate tolerance US 2006-282915
Soybean A2704-12 Glufosinate tolerance WO 2006/108674
Soybean A5547-35 Glufosinate tolerance WO 2006/108675
Soybean DP-305423-1 High oleic acid / ALS inhibitor WO 2008/054747 tolerance
Rice GAT-OS2 Glufosinate tolerance WO 01/83818
Rice GAT-OS3 Glufosinate tolerance US 2008-289060
Rice PE-7 Insect resistance (CrylAc) WO 2008/1 14282
Oilseed rape MS-B2 Male sterility WO 01/31042
Oilseed rape MS-BN1/RF-BN1 Male sterility/restoration WO 01/41558
Oilseed rape RT73 Glyphosate resistance WO 02/36831
Cotton CE43-67B Insect resistance (CrylAb) WO 2006/128573
Cotton CE46-02A Insect resistance (CrylAb) WO 2006/128572
Cotton CE44-69D Insect resistance (CrylAb) WO 2006/128571
Cotton 1 143-14A Insect resistance (CrylAb) WO 2006/128569
Cotton 1 143-51 B Insect resistance (CrylAb) WO 2006/128570
Cotton T342-142 Insect resistance (CrylAb) WO 2006/128568
Cotton event3006-210-23 Insect resistance (CrylAc) WO 2005/103266
Cotton PV-GHGT07 (1445) Glyphosate tolerance US 2004-148666
Cotton MON88913 Glyphosate tolerance WO 2004/072235
Cotton EE-GH3 Glyphosate tolerance WO 2007/017186
Cotton T304-40 Insect-resistance (CrylAb) WO2008/122406
Cotton Cot202 Insect resistance (VI P3) US 2007-067868
Cotton LLcotton25 Glufosinate resistance WO 2007/017186
Cotton EE-GH5 Insect resistance (CrylAb) WO 2008/122406
Cotton event 281-24-236 Insect resistance (Cryl F) WO 2005/103266
Cotton Cot 102 Insect resistance (Vip3A) US 2006-130175
Cotton MON 15985 Insect resistance (Cry1A Cry2Ab) US 2004-250317
Bent Grass Asr-368 Glyphosate tolerance US 2006-162007
Brinjal EE-1 Insect resistance (CrylAc) WO 2007/091277
Among the diseases of plants or crops that can be controlled by the method according to the invention, mention can be made of :
Powdery mildew diseases such as :
Blumeria diseases, caused for example by Blumeria graminis ;
Podosphaera diseases, caused for example by Podosphaera leucotricha ;
Sphaerotheca diseases, caused for example by Sphaerotheca fuliginea ;
Uncinula diseases, caused for example by Uncinula necator ; Rust diseases such as :
Gymnosporangium diseases, caused for example by Gymnosporangium sabinae ;
Hemileia diseases, caused for example by Hemileia vastatrix ;
Phakopsora diseases, caused for example by Phakopsora pachyrhizi or Phakopsora meibomiae ;
Puccinia diseases, caused for example by Puccinia recondite, Puccinia graminis or
Puccinia striiformis;
Uromyces diseases, caused for example by Uromyces appendiculatus ;
Oomycete diseases such as :
Albugo diseases caused for example by Albugo Candida;
Bremia diseases, caused for example by Bremia lactucae ;
Peronospora diseases, caused for example by Peronospora pisi or P. brassicae ;
Phytophthora diseases, caused for example by Phytophthora infestans ;
Plasmopara diseases, caused for example by Plasmopara viticola ;
Pseudoperonospora diseases, caused for example by Pseudoperonospora humuli or
Pseudoperonospora cubensis ;
Pythium diseases, caused for example by Pythium ultimum ;
Leafspot, leaf blotch and leaf blight diseases such as :
Alternaria diseases, caused for example by Alternaria solani ;
Cercospora diseases, caused for example by Cercospora beticola ;
Cladiosporum diseases, caused for example by Cladiosporium cucumerinum ;
Cochliobolus diseases, caused for example by Cochliobolus sativus (Conidiaform: Drechslera, Syn: Helminthosporium) or Cochliobolus miyabeanus ;
Colletotrichum diseases, caused for example by Colletotrichum lindemuthanium ;
Cycloconium diseases, caused for example by Cycloconium oleaginum ;
Diaporthe diseases, caused for example by Diaporthe citri ;
Elsinoe diseases, caused for example by Elsinoe fawcettii ;
Gloeosporium diseases, caused for example by Gloeosporium laeticolor ;
Glomerella diseases, caused for example by Glomerella cingulata ;
Guignardia diseases, caused for example by Guignardia bidwelli ;
Leptosphaeria diseases, caused for example by Leptosphaeria maculans ; Leptosphaeria nodorum ;
Magnaporthe diseases, caused for example by Magnaporthe grisea ;
Mycosphaerella diseases, caused for example by Mycosphaerella graminicola ; Mycosphaerella arachidicola ; Mycosphaerella fijiensis ;
Phaeosphaeria diseases, caused for example by Phaeosphaeria nodorum ;
Pyrenophora diseases, caused for example by Pyrenophora teres, or Pyrenophora tritici repentis;
Ramularia diseases, caused for example by Ramularia collo-cygni , or Ramularia areola;
Rhynchosporium diseases, caused for example by Rhynchosporium secalis ;
Septoria diseases, caused for example by Septoria apii or Septoria lycopercisi ;
Typhula diseases, caused for example by Typhula incarnata ;
Venturia diseases, caused for example by Venturia inaequalis ; Root, Sheath and stem diseases such as :
Corticium diseases, caused for example by Corticium graminearum ;
Fusarium diseases, caused for example by Fusarium oxysporum ;
Gaeumannomyces diseases, caused for example by Gaeumannomyces graminis ;
Rhizoctonia diseases, caused for example by Rhizoctonia solani ;
Sarocladium diseases caused for example by Sarocladium oryzae;
Sclerotium diseases caused for example by Sclerotium oryzae;
Tapesia diseases, caused for example by Tapesia acuformis ;
Thielaviopsis diseases, caused for example by Thielaviopsis basicola ;
Ear and panicle diseases such as :
Alternaria diseases, caused for example by Alternaria spp. ;
Aspergillus diseases, caused for example by Aspergillus flavus ;
Cladosporium diseases, caused for example by Cladosporium spp. ;
Claviceps diseases, caused for example by Claviceps purpurea ;
Fusarium diseases, caused for example by Fusarium culmorum ;
Gibberella diseases, caused for example by Gibberella zeae ;
Monographella diseases, caused for example by Monographella nivalis ;
Smut and bunt diseases such as :
Sphacelotheca diseases, caused for example by Sphacelotheca reiliana ;
Tilletia diseases, caused for example by Tilletia caries ;
Urocystis diseases, caused for example by Urocystis occulta ;
Ustilago diseases, caused for example by Ustilago nuda ;
Fruit rot and mould diseases such as :
Aspergillus diseases, caused for example by Aspergillus flavus ;
Botrytis diseases, caused for example by Botrytis cinerea ;
Penicillium diseases, caused for example by Penicillium expansum ;
Rhizopus diseases caused by example by Rhizopus stolonifer
Sclerotinia diseases, caused for example by Sclerotinia sclerotiorum ;
Verticilium diseases, caused for example by Verticilium alboatrum ;
Seed and soilborne decay, mould, wilt, rot and dam ping-off diseases :
Alternaria diseases, caused for example by Alternaria brassicicola
Aphanomyces diseases, caused for example by Aphanomyces euteiches
Ascochyta diseases, caused for example by Ascochyta lentis
Aspergillus diseases, caused for example by Aspergillus flavus
Cladosporium diseases, caused for example by Cladosporium herbarum
Cochliobolus diseases, caused for example by Cochliobolus sativus
(Conidiaform: Drechslera, Bipolaris Syn: Helminthosporium);
Colletotrichum diseases, caused for example by Colletotrichum coccodes;
Fusarium diseases, caused for example by Fusarium culmorum;
Gibberella diseases, caused for example by Gibberella zeae;
Macrophomina diseases, caused for example by Macrophomina phaseolina
Monographella diseases, caused for example by Monographella nivalis; Penicillium diseases, caused for example by Penicillium expansum
Phoma diseases, caused for example by Phoma lingam
Phomopsis diseases, caused for example by Phomopsis sojae;
Phytophthora diseases, caused for example by Phytophthora cactorum;
Pyrenophora diseases, caused for example by Pyrenophora graminea
Pyricularia diseases, caused for example by Pyricularia oryzae;
Pythium diseases, caused for example by Pythium ultimum;
Rhizoctonia diseases, caused for example by Rhizoctonia solani;
Rhizopus diseases, caused for example by Rhizopus oryzae
Sclerotium diseases, caused for example by Sclerotium rolfsii;
Septoria diseases, caused for example by Septoria nodorum;
Typhula diseases, caused for example by Typhula incarnata;
Verticillium diseases, caused for example by Verticillium dahliae ;
Canker, broom and dieback diseases such as :
Nectria diseases, caused for example by Nectria galligena ;
Blight diseases such as :
Monilinia diseases, caused for example by Monilinia laxa ;
Leaf blister or leaf curl diseases such as :
Exobasidium diseases caused for example by Exobasidium vexans
Taphrina diseases, caused for example by Taphrina deformans ;
Decline diseases of wooden plants such as :
Esca diseases, caused for example by Phaemoniella clamydospora ;
Eutypa dyeback, caused for example by Eutypa lata ;
Ganoderma diseases caused for example by Ganoderma boninense;
Rigidoporus diseases caused for example by Rigidoporus lignosus
Diseases of Flowers and Seeds such as
Botrytis diseases caused for example by Botrytis cinerea;
Diseases of Tubers such as
Rhizoctonia diseases caused for example by Rhizoctonia solani;
Helminthosporium diseases caused for example by Helminthosporium solani;
Club root diseases such as
Plasmodiophora diseases, cause for example by Plamodiophora brassicae.
Diseases caused by Bacterial Organisms such as
Xanthomonas species for example Xanthomonas campestris pv. oryzae;
Pseudomonas species for example Pseudomonas syringae pv. lachrymans;
Erwinia species for example Erwinia amylovora.
The composition according to the invention may also be used against fungal diseases liable to grow on or inside timber. The term "timber" means all types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood. The method for treating timber according to the invention mainly consists in contacting one or more compounds according to the invention or a composition according to the invention; this includes for example direct application, spraying, dipping, injection or any other suitable means.
The dose of active compound usually applied in the method of treatment according to the invention is generally and advantageously from 10 to 800 g/ha, preferably from 50 to 300 g/ha for applications in foliar treatment. The dose of active substance applied is generally and advantageously from 2 to 200 g per 100 kg of seed, preferably from 3 to 150 g per 100 kg of seed in the case of seed treatment.
It is clearly understood that the doses indicated herein are given as illustrative examples of the method according to the invention. A person skilled in the art will know how to adapt the application doses, notably according to the nature of the plant or crop to be treated.
The compounds or mixtures according to the invention can also be used for the preparation of composition useful to curatively or preventively treat human or animal fungal diseases such as, for example, mycoses, dermatoses, trichophyton diseases and candidiases or diseases caused by Aspergillus spp., for example Aspergillus fumigatus.
The various aspects of the invention will now be illustrated with reference to the following table of compound examples and the following preparation or efficacy examples. Table 1 illustrates in a non-limiting manner examples of compounds of formula (I) according to the invention
Figure imgf000045_0001
In table 1 , unless otherwise specified, M+H (Apcl+) means the molecular ion peak plus 1 a.m.u. (atomic mass unit) as observed in mass spectroscopy via positive atmospheric pressure chemical ionisation.
In table 1 , the logP values were determined in accordance with EEC Directive 79/831 Annex V.A8 by HPLC (High Performance Liquid Chromatography) on a reversed-phase column (C 18), using the method described below :
Temperature: 40°C ; Mobile phases : 0.1 % aqueous formic acid and acetonitrile ; linear gradient from 10% acetonitrile to 90% acetonitrile.
Calibration was carried out using unbranched alkan-2-ones (comprising 3 to 16 carbon atoms) with known logP values (determination of the logP values by the retention times using linear interpolation between two successive alkanones). lambda-max-values were determined using UV-spectra from 200 nm to 400 nm and the peak values of the chromatographic signals. Table 1:
Figure imgf000046_0001
Figure imgf000047_0001
Figure imgf000048_0001
Figure imgf000049_0001
Figure imgf000050_0001
Figure imgf000051_0001
Figure imgf000052_0001
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
Mass
Ξ logP c X1 X2 Y Z1 Q1 Q2 Q3 Q4 B (M+H) x
LU
#
241 Me O cyclopropyl CH2 2-chlorophenyl 4.67 440
#
242 Me O cyclopropyl CH2 2,4-dichlorophenyl 5.31 474
#
4.34 +
243 Me O cyclopropyl CH2 phenyl 406
4.41 ( )
#
244 Me O cyclopropyl O phenyl 3.89 408
#
245 Me O H O phenyl 3.52 368
#
246 CI Me 0 H O phenyl 3.76 384
Mass
Ξ logP
c X1 X2 Y Z1 Q1 Q2 Q3 Q4 B (M+H) x
LU
247 Me O cyclopropyl O phenyl 4.21 408
#
5.36 +
248 Me O cyclopropyl O 2,4,6-trichlorophenyl 510
5.74(1 )
4.87 +
249 Me O cyclopropyl O 2,4-dichlorophenyl 476
5.31 (1 )
4.59 +
250 Me O cyclopropyl O 2,6-dichlorophenyl 476
4.87(1 )
#
4.25 +
251 Me O cyclopropyl O 2-chlorophenyl 442
4.59(1 )
4.06 +
252 CI Me O cyclopropyl O phenyl 424
4.41 ( )
Figure imgf000067_0001
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0001
Figure imgf000074_0001
Figure imgf000075_0001
Figure imgf000076_0001
Figure imgf000077_0001
Mass
Ξ logP
c X1 X2 Y Z1 Q1 Q2 Q3 Q4 B (M+H) x
LU
347 CI Me O cyclopropyl CH2 H 4.16 372
#
348 CI Me O H C(Me)2 Me 4.15 348
349 Me O H C(Me)2 Me 3.79 332
350 Me O cyclopropyl C(Me)2 Me 4.71 372
#
351 Me O cyclopropyl Me 3.50 362
352 CI Me O cyclopropyl Me 3.73 378
Figure imgf000079_0001
Mass
Ξ logP c X1 X2 Y Z1 Q1 Q2 Q3 Q4 B (M+H) x
LU
#
359 CI Me O H CH(Me) CH2 t-Bu 5.28
#
4.85
360 Me O H CH(Me) CH2 t-Bu isomer
A
#
4.89
361 Me O H CH(Me) CH2 t-Bu isomer
B
Me
362 CI Me O H CH2 Me 4.44 362
Me Me
Me
363 Me O H CH2 Me 4.23 346
Me Me
#
364 Me O H CH2 CH2 Me 3.49
Figure imgf000081_0001
0
L Mass
Ξ logP
c X1 X2 Y Z1 Q1 Q2 Q3 Q4 B (M+H) x
LU
372 Me O cyclopropyl cyclohexyl 5.28 398
#
373 CI Me O cyclopropyl cyclohexyl 5.59 414
#
374 Me O H cyclohexyl 4.34 358
#
375 CI Me O H cyclohexyl 4.56 374
#
376 Me O cyclopropyl cyclohex-1-en-1-yl 4.88 396
#
377 CI Me 0 cyclopropyl cyclohex-1-en-1-yl 5.17 412
Figure imgf000083_0001
Figure imgf000084_0001
Note ' : mixture of two or more isomers ;
Note (2) : mass M ;
Note : # denotes the point of attachement to the amide moiety ;
* denotes the point of attachement to the side chain.
Table 2 provides the NMR data ( H ) of a selected number of compounds from table 1.
The H-NMR data of selected examples are stated in the form of H-NMR peak lists. For each signal peak, the δ value in ppm and the signal intensity in brackets are listed: Table 2:
Example 306
Solvent: DMSO-d6
7.7657 (0.35) 7.7492 (0.95) 7.7287 (0.77) 7.5612 (0.53) 7.5402 (0.54) 7.2237 (0.57) 7.2191 (1.23) 7.1717 (0.88) 7.0889 (1 .21 ) 7.0842 (2.72) 7.0368 (1.88) 6.9542 (0.63) 6.9495 (1.34) 6.9022 (0.96) 4.2971 (0.33) 4.2868 (0.39) 4.2812 (0.4) 4.2745 (0.38) 3.809 (0.82) 3.7885 (1.43) 3.7734 (16) 3.5677 (1.1 ) 3.3526 (0.32) 3.3481 (0.37) 3.3056 (589.57) 2.6737 (0.49) 2.6691 (0.69) 2.6646 (0.5) 2.5392 (0.93) 2.5225 (1.71 ) 2.5177 (2.67) 2.5091 (36.9) 2.5047 (72.29) 2.5001 (97.2) 2.4957 (66.33) 2.4912 (30.83) 2.3314 (0.46) 2.3268 (0.67) 2.3221 (0.45) 2.0692 (0.62) 1.9867 (0.48) 1 .9287 (0.33) 1.923 (0.51 ) 1 .9097 (0.85) 1.9035 (0.51 ) 1 .891 1 (1.05) 1.8785 (1.2) 1.8592 (1.36) 1.8506 (1.21 ) 1.8422 (0.94) 1.8313 (1.03) 1.8192 (0.94) 1.8121 (0.57) 1.8006 (0.52) 1 .7597 (0.42) 1.7507 (0.7) 1.7385 (0.87) 1.7295 (1.16) 1 .7182 (1.08) 1.7093 (1.58) 1 .6878 (1.52) 1.677 (1.17) 1.6629 (0.77) 1.6562 (0.58) 1.6426 (0.63) 1 .6312 (0.49) 1.6235 (0.64) 1.61 1 (0.8) 1 .6002 (0.91 ) 1.5904 (0.96) 1.5808 (0.87) 1.5736 (0.92) 1 .5688 (0.84) 1.5585 (1.1 ) 1.5525 (0.92) 1.5475 (1 ) 1.5414 (1.24) 1.5322 (0.97) 1.5217 (1.04) 1.51 13 (1.04) 1.5051 (0.96) 1.5012 (0.94) 1.4913 (1.15) 1.4839 (1.19) 1.4653 (1.37) 1 .4543 (1.19) 1.4486 (1.26) 1.4419 (1.25) 1.4356 (1.12) 1.4168 (0.66) 1.4121 (0.66) 1.3436 (0.54) 1.3228 (0.66) 1.314 (0.65) 1.2897 (1 ) 1.2779 (1.48) 1 .2688 (1.72) 1.2634 (1.75) 1.2593 (1.83) 1.2484 (3.33) 1.2398 (2.67) 1 .2314 (2.89) 1.222 (1.92) 1.2132 (1.46) 1.2035 (1.22) 1.1927 (1.16) 1.1827 (1 .56) 1.1748 (1.27) 1.1612 (1.3) 1.1518 (1.22) 1.1395 (0.82) 1.1305 (0.94) 1.1 156 (0.45) 1.1092 (0.49) 0.8616 (2.28) 0.8443 (4.9) 0.8316 (4.27) 0.8273 (2.42) 0.8195 (0.95) 0.8138 (1.03) -0.0002 (2.56)
Example 312
Solvent: CD3CN
7.2157 (1.27) 7.1527 (0.7) 7.1439 (1.52) 7.131 1 (1.2) 7.1259 (2.77) 7.0629 (1.51 ) 7.054 (3.13) 7.0412 (2.33) 7.0361 (1.36) 6.9731 (0.75) 6.9642 (1 .63) 6.9515 (1.24) 4.5202 (0.48) 4.5131 (0.45) 4.5049 (0.47) 4.4779 (0.52) 4.4698 (0.42) 4.4629 (0.51 ) 4.1307 (0.53) 4.1 175 (0.96) 4.1044 (1 .09) 4.0913 (0.7)
3.8568 (1 1.44) 3.8556 (10.96) 3.8544 (10.51 ) 3.8501 (16) 2.1768 (124.26) 1.9944 (0.35) 1.9921 (0.73) 1.9815 (0.75) 1.9792 (0.76) 1.9732 (0.64) 1.9709 (0.98) 1.9665 (3.26) 1.9605 (0.94) 1 .9584 (1.76) 1.9543 (1.54) 1.9504 (16.34) 1.9463 (32.24) 1.9422 (47.65) 1.9382 (30.99) 1.934 (15.22) 1.9292 (0.8) 1.9253 (0.37) 1.9228 (0.35) 1.8794 (0.36) 1.8749 (0.32) 1.8704 (0.41 ) 1.8658 (0.68) 1 .8622 (0.56)
1.8569 (0.7) 1.8527 (0.7) 1.8477 (0.43) 1.8436 (0.58) 1.8357 (0.58) 1.8318 (0.42) 1.8275 (0.46) 1.8234 (0.35) 1.8197 (0.44) 1 .7568 (0.49) 1.7485 (0.64) 1.7466 (0.62) 1.742 (0.64) 1.7343 (1.03) 1.7267 (0.83) 1.7235 (1.17) 1 .7201 (1.28) 1.7142 (1.31 ) 1 .7062 (1.7) 1.6915 (1.39) 1.6875 (1.54) 1.6817 (1.52)
1.6749 (1.61 ) 1 .67 (1.46) 1 .6645 (1.77) 1.66 (1 .31 ) 1.6581 (1.48) 1.655 (1 .59) 1.6532 (1.5) 1.6473 (1.69) 1 .644 (1.65) 1.6365 (1.74) 1.6338 (1.49) 1.6313 (1.24) 1.6267 (1.66) 1.6225 (2.13) 1.6157 (1.88) 1.61 1 (1.9) 1.6094 (1.82) 1.6045 (1.44) 1.5986 (1.48) 1.5914 (0.82) 1.5879 (0.78) 1.5838 (0.58) 1.5789 (0.36) 1.5705 (0.34) 1.5177 (0.48) 1.5064 (0.79) 1.5025 (0.6) 1.4957 (0.96) 1.4917 (0.87) 1.4839 (1.17) 1.4794 (0.78) 1 .473 (0.97) 1.4678 (0.77) 1.4615 (0.5) 1.4563 (0.43) 1.4505 (0.4) 1 .4363 (1 1 .79) 1.3752 (0.33) 1.365 (0.69) 1 .3585 (0.46) 1.3503 (0.77) 1.3454 (0.8) 1.3363 (0.78) 1.3293 (0.75) 1.3218 (0.58) 1.3159 (0.94) 1 .3104 (0.69) 1.3006 (0.53) 1 .2981 (0.56) 1.2931 (0.9) 1.2882 (0.72) 1.2757 (0.49) 1.2704 (0.6) 1.2301 (0.34) 1.2249 (0.34) 1.212 (0.47) 1.2077 (0.73) 1.2041 (0.47) 1.203 (0.47) 1.1896 (0.74) 1.1848 (0.89) 1 .175 (0.51 ) 1.171 1 (0.52) 1.1668 (0.33) 1.1622 (1 ) 1.1529 (0.69) 1.1487 (0.76) 1.1392 (0.63) 1 .1 14 (0.5) 1.1023 (0.97) 1.0921 (0.75) 1.0881 (0.76) 1.0797 (0.54) 1.078 (0.77) 1.0698 (0.43) 1 .0658 (0.44) 1.0557 (0.69) 1.0485 (0.74) 1.0424 (0.48) 1.0391 (0.33) 1.0313 (0.68) 1.026 (0.75) 1.0203 (0.4) 1.0091 (0.54) 1.0054 (0.57) 1.0028 (0.42) 0.9993 (0.51 ) 0.9874 (0.49) 0.983 (0.61 ) 0.9816 (0.59) 0.9773 (0.45) 0.9654 (0.41 ) 0.9593 (0.4) 0.904 (3.49) 0.8926 (9.38) 0.8817 (13.38) 0.8713 (7.79) 0.8695 (6.32) 0.8616 (9.02) 0.858 (0.81 ) 0.8506 (8.87) 0.8451 (9.19) 0.8432 (10.55) 0.8423 (1 1.04) 0.834 (8.78) 0.8315 (10.76) 0.8235 (5.81 ) 0.8127 (5.69) 0.8096 (3.91 ) 0.7987 (3.56) 0.6928 (6.25) 0.682 (6.1 1 ) -0.0002 (1.09)
Example 316
Solvent: CD3CN
7.2147 (0.44) 7.2082 (0.82) 7.183 (0.78) 7.1327 (0.56) 7.0797 (0.89) 7.0733 (1.67) 7.0482 (1.6) 6.9979 (1.1 1 ) 6.9448 (0.46) 6.9384 (0.84) 6.9134 (0.81 ) 6.8631 (0.57) 4.5032 (0.35) 4.4808 (0.34) 4.1 165 (0.64) 4.0966 (0.75) 4.0765 (0.46) 3.7434 (12.99) 2.1409 (72.15) 1 .9827 (0.47) 1.971 1 (1 .8) 1.9631 (1.7) 1.957 (1.86) 1 .9512 (10.83) 1.945 (19.73) 1 .9389 (27.64) 1.9327 (19.24) 1.9265 (9.8) 1.91 14 (0.76) 1 .9003 (0.56) 1.8964 (0.48) 1.8899 (0.56) 1.8817 (0.53) 1.8755 (0.51 ) 1.8679 (0.35) 1.8622 (0.48) 1.8592 (0.45) 1.8528 (0.43) 1.8399 (0.47) 1.8272 (0.43) 1.7736 (0.38) 1.7673 (0.43) 1.7612 (0.34) 1 .7546 (0.42) 1.7457 (0.54) 1.7335 (0.73) 1.7254 (0.74) 1.7132 (1.07) 1.7073 (0.93) 1.6958 (1.31 ) 1 .6897 (1.17) 1.6794 (1.69) 1.6734 (1 .59) 1.6701 (1.53) 1.6634 (1.78) 1.6606 (1.75) 1.6568 (1.88) 1.6473 (1.94) 1.6389 (1.73) 1.631 (2.19) 1.6149 (1.88) 1.61 1 (1.83) 1.5975 (1.75) 1.5885 (1.04) 1.5825 (1.12) 1 .579 (1.04) 1.5683 (0.68) 1.5638 (0.65) 1.5006 (0.44) 1.4847 (0.45) 1.4774 (0.45) 1.4691 (0.64) 1.4609 (0.54) 1 .4527 (0.64) 1.4371 (2.96) 1.4267 (0.56) 1.4185 (0.55) 1.4093 (0.35) 1.4012 (0.32) 1 .3917 (0.36) 1.3682 (0.39) 1 .361 (0.58) 1.3419 (0.79) 1.3257 (0.54) 1.3147 (0.82) 1.2989 (0.41 ) 1.2884 (0.67) 1.2813 (0.77) 1.2738 (0.54) 1.2549 (0.43) 1.2471 (0.41 ) 1 .2215 (0.48) 1.2176 (0.39) 1.21 (0.56) 1.2037 (1 ) 1.1857 (0.84) 1.1742 (0.53) 1.1682 (0.34) 1.1543 (0.7) 1.14 (0.5) 1.1346 (0.53) 1.1 199 (0.42) 1.0958 (0.51 ) 1.0801 (0.54) 1.0748 (0.53) 1.0592 (0.58) 1 .0553 (0.45) 1.0514 (0.38) 1.0461 (0.59) 1.0409 (0.46) 1.0265 (0.52) 1.0197 (0.52) 1 .0018 (0.44) 0.9933 (0.6) 0.9749 (0.4) 0.9679 (0.46) 0.9596 (0.34) 0.9418 (0.32) 0.8966 (3.97) 0.8926 (2.77) 0.8804 (7.7) 0.8759 (3.22) 0.8662 (5.67) 0.858 (5.97) 0.8527 (3.83) 0.8416 (16) 0.8345 (4.77) 0.8252 (10.7) 0.8182 (4.04) 0.8049 (2.39) 0.7886 (2.17) 0.6955 (3.9) 0.6791 (3.76) 0.008 (0.47) -0.0002 (1 1.82) -0.0086 (0.45)
Example 319
Solvent: DMSO-d6
7.2105 (0.41 ) 7.0755 (0.92) 7.0349 (0.53) 6.9408 (0.45) 4.0393 (0.45) 4.0215 (0.45) 3.79 (0.48) 3.7742 (3.73) 3.3093 (168.59) 2.5228 (0.43) 2.5181 (0.66) 2.5094 (9.06) 2.505 (17.8) 2.5005 (24.03) 2.496 (16.41 ) 2.4915 (7.68) 1.9867 (2.05) 1.8508 (0.33) 1.5979 (0.37) 1.5843 (0.37) 1 .4587 (0.38) 1.1929 (0.79) 1 .1751 (1.58) 1.1683 (0.37) 1.1573 (1 .02) 1.1472 (1.02) 1.1219 (0.84) 1.1 154 (0.51 ) 1.0992 (0.74) 0.8486 (1.04) 0.8438 (1 .07) 0.8324 (16) 0.8221 (1.24) 0.8126 (9.14) 0.8007 (0.7) 0.7906 (0.98) 0.7852 (0.8) -0.0002 (1.73)
Example 326
Solvent: DMSO-d,
7.6444 (1.62) 7.6244 (1 .63) 7.2284 (1.97) 7.0936 (4.54) 6.9589 (2.17) 3.7683 (14.62) 3.7159 (0.32) 3.7036 (0.41 ) 3.6844 (0.77) 3.6745 (0.95) 3.6649 (0.83) 3.6549 (0.95) 3.6454 (0.78) 3.6363 (0.47) 3.6258 (0.42) 3.4746 (0.38) 3.3181 (533.16) 3.2959 (4.34) 3.2707 (0.33) 2.6747 (0.34) 2.6702 (0.44) 2.5401 (0.67) 2.5233 (1.66) 2.5099 (24.83) 2.5055 (46.48) 2.501 1 (60.77) 2.4967 (42.16) 2.4923 (20.06) 2.3279 (0.38) 2.0689 (1.12) 1.8494 (1.07) 1.8164 (1.83) 1.7797 (0.99) 1 .7332 (1.01 ) 1.7254 (0.81 ) 1 .717 (0.63) 1.7081 (0.93) 1.7009 (1.22) 1.6936 (0.97) 1.6638 (1.03) 1.6331 (1 .07) 1.3223 (1 ) 1.2895 (2.73) 1.2784 (3.48) 1 .2438 (16) 1.2067 (2.19) 1.1926 (2.42) 1.1834 (2.87) 1.1768 (2.89) 1.152 (1.34) 1 .1221 (0.41 ) 1.1 14 (0.37) 0.9417 (0.78) 0.912 (2.05) 0.8819 (2.36) 0.8729 (3.89) 0.8563 (1 1.23) 0.839 (4.04) 0.8132 (0.44) 0.8056 (0.48) 0.7821 (0.98) 0.7744 (0.97) 0.7521 (0.89) 0.7439 (0.88) 0.7216 (0.36) 0.008 (0.37) -0.0002 (8.1 )
Example 330
Solvent: DMSO-d6
7.4069 (1.5) 7.3849 (1.5) 7.1692 (2.38) 7.0345 (5.15) 6.9 (2.63) 4.1 1 14 (1.13) 4.1029 (1.1 1 ) 3.8657 (0.57) 3.7749 (16) 3.7578 (0.4) 3.3014 (141.26) 2.5224 (0.75) 2.5176 (1.21 ) 2.509 (12.2) 2.5046 (23) 2.5001 (30.25) 2.4957 (20.51 ) 2.4912 (9.48) 2.0696 (2.94) 1.6631 (1.28) 1.6504 (1.04) 1.6372 (0.78) 1.619 (0.42) 1.5971 (1.06) 1.5906 (1.02) 1.5618 (1.59) 1.5373 (1.03) 1.4726 (1.14) 1.4491 (3.19) 1.4341 (5) 1.4087 (1.02) 1.3544 (0.5) 1.3464 (0.46) 1.3271 (1.06) 1 .3202 (1.1 ) 1.2941 (1 .69) 1.2661 (1.85) 1 .2546 (2.18) 1.2321 (6.94) 1.2287 (7.18) 1.2199 (8.09) 1.2036 (2.68) 1.1809 (0.76) 1.1628 (0.93) 1 .1444 (1 .04) 1.1255 (0.94) 1.1076 (0.48) 0.8495 (3.55) 0.8404 (3.19) 0.8324 (9.9) 0.8149 (2.86) -0.0002 (1.5)
Example 333
Solvent: DMSO-d6
7.6924 (0.47) 7.6706 (0.46) 7.433 (0.86) 7.41 16 (0.88) 7.201 (0.56) 7.1647 (1 .15) 7.066 (1.2) 7.03 (2.44) 6.9313 (0.62) 6.8954 (1.23) 4.139 (0.51 ) 4.1 17 (0.67) 4.1084 (0.65) 3.7753 (12.35) 3.7007 (0.39) 3.4947 (0.33) 3.4863 (0.36) 3.473 (0.49) 3.4654 (0.68) 3.4449 (0.32) 3.436 (0.32) 3.322 (53.06) 2.9918 (0.62) 2.8915 (0.45) 2.7326 (0.35) 2.51 (12.59) 2.5058 (23.15) 2.5015 (29.75) 2.4972 (20.92) 1.822 (0.34) 1.7828 (0.53) 1.7616 (0.45) 1.6633 (1.29) 1 .6523 (1.07) 1.6382 (0.84) 1 .5947 (0.78) 1.5901 (0.76) 1 .5604 (0.75) 1.5292 (0.91 ) 1.5196 (1 .04) 1.5028 (1.3) 1.493 (1.07) 1.475 (1.52) 1 .4592 (1.79) 1.4426 (3.18) 1.4313 (3.74) 1.41 15 (1.62) 1.3567 (0.99) 1.3359 (0.96) 1.329 (1.01 ) 1.3026 (1.34) 1.2767 (1.57) 1.2464 (1 .93) 1.2299 (1.74) 1.2104 (1.28) 1.1987 (1.04) 1.1891 (1.02) 1 .1804 (1.06) 1.1603 (1.42) 1.1529 (1 .83) 1.1389 (2.94) 1.1265 (3.48) 1.1038 (1.13) 1.0792 (0.66) 1 .0646 (0.62) 1.0506 (0.92) 1.0341 (0.99) 1.0267 (0.8) 1.0055 (0.55) 0.9976 (0.46) 0.9849 (0.36) 0.9741 (0.54) 0.9689 (0.53) 0.9435 (0.38) 0.8783 (0.79) 0.8719 (1.14) 0.867 (1.83) 0.8616 (1.43) 0.8557 (1.77) 0.8503 (2.23) 0.8319 (12.16) 0.8201 (10.95) 0.8155 (16) 0.8037 (9.49) 0.7994 (5.7) 0.7742 (0.88) 0.7674 (0.75) 0.7579 (0.61 ) 0.7499 (0.49) 0.7414 (0.45) 0.7249 (0.36) 0.7083 (0.32) -0.0002 (2.31 )
Example 334
Solvent: DMSO-d,
7.8032 (0.32) 7.7607 (0.59) 7.7382 (0.6) 7.1657 (0.89) 7.1602 (0.5) 7.0306 (2.02) 7.025 (0.98) 6.8955 (1 ) 6.8899 (0.56) 3.8645 (9.89) 3.7287 (0.32) 3.7191 (0.34) 3.7063 (0.44) 3.6957 (0.45) 3.2898 (163.83) 2.668 (0.34) 2.538 (0.69) 2.5214 (1 ) 2.5165 (1.6) 2.5081 (18.42) 2.5035 (37.5) 2.499 (50.91 ) 2.4944 (35.99) 2.4898 (16.62) 2.067 (16) 1.9377 (0.33) 1.9209 (0.4) 1 .9138 (0.41 ) 1.9069 (0.4) 1.8949 (0.37) 1.8251 (0.51 ) 1 .817 (0.53) 1.6918 (1.19) 1.6678 (1.49) 1.567 (0.4) 1.5486 (0.36) 1 .5339 (0.41 ) 1.5183 (0.46) 1 .5023 (0.43) 1.3433 (0.36) 1.3148 (0.72) 1.2849 (0.5) 1.2778 (0.54) 1.2473 (0.8) 1.2226 (0.97) 1.2015 (0.64) 1.1 161 (0.59) 1 .1088 (0.6) 1.0994 (0.52) 1.0834 (1 ) 1.0703 (0.54) 1.0579 (0.53) 1.0498 (0.78) 1.032 (0.48) 1.0151 (0.52) 0.9969 (0.48) 0.9894 (0.44) 0.981 (0.41 ) 0.9633 (0.36) 0.9474 (0.47) 0.9377 (0.43) 0.9188 (0.44) 0.915 (0.45) 0.9092 (0.48) 0.8867 (0.35) 0.8766 (0.44) 0.8628 (2.61 ) 0.8486 (6.05) 0.8429 (5.04) 0.8323 (5.48) 0.8285 (4.65) 0.8256 (4.81 ) 0.8122 (2.46) 0.7999 (0.33) 0.7217 (4.69) 0.7152 (2.8) 0.7055 (4.49) 0.6981 (2.47) -0.0002 (6.7)
Example 335
Solvent: DMSO-d6
7.636 (1.01 ) 7.6135 (1.02) 7.5345 (0.52) 7.5127 (0.53) 7.1804 (0.83) 7.1666 (1.59) 7.0452 (1.78) 7.0315 (3.51 ) 7.0257 (0.5) 6.9101 (0.92) 6.8965 (1.74) 4.3874 (0.38) 4.3812 (0.41 ) 4.365 (0.42) 4.3431 (0.74) 4.3364 (0.73) 4.3205 (0.73) 4.3145 (0.67) 3.8684 (16) 3.2902 (124.98) 3.2673 (2.37) 2.5383 (0.44) 2.5214 (0.78) 2.5083 (1 1 .52) 2.5038 (22.91 ) 2.4992 (30.77) 2.4946 (21.63) 2.4901 (10.03) 2.0673 (1.43) 1 .7708 (0.79) 1.7551 (1 ) 1.7474 (0.89) 1.7088 (1.49) 1 .6932 (2.05) 1.6337 (0.4) 1.624 (0.52) 1 .6171 (0.69) 1.6081 (0.85) 1.6006 (0.92) 1.5923 (0.92) 1.5838 (0.86) 1.5758 (0.76) 1.5675 (0.64) 1.5596 (0.39) 1.437 (1 .78) 1.4241 (1.59) 1.4147 (1.86) 1.3974 (1.7) 1.3842 (1.27) 1.3764 (1.47) 1.3598 (1.07) 1 .3521 (1.19) 1.3452 (0.9) 1.3359 (0.85) 1.3284 (0.92) 1.3203 (0.59) 1.31 19 (0.58) 1.3026 (0.65) 1.2933 (0.5) 1.2683 (1.49) 1 .2607 (1.06) 1.2427 (1.97) 1.2359 (2.08) 1.2278 (1 .24) 1.212 (2.04) 1 .203 (1.47) 1.1931 (1.29) 1 .1718 (0.9) 1.1632 (0.76) 1 .1384 (0.99) 1.1 136 (0.84) 1.1064 (0.81 ) 1.0838 (0.42) 0.9178 (0.71 ) 0.9078 (1 ) 0.8984 (0.59) 0.8928 (0.82) 0.883 (1 .57) 0.8707 (8.87) 0.8632 (2.21 ) 0.8542 (8.57) 0.8467 (6.31 ) 0.8301 (5.28) 0.82 (0.91 ) 0.8125 (1.28) 0.7966 (8.24) 0.7844 (13.33) 0.7806 (8.71 ) 0.7685 (8.15) 0.7151 (5.15) 0.6988 (4.96) -0.0002 (3.34)
Example 343
Solvent: DMSO-d6
7.652 (1.66) 7.6298 (1 .68) 7.2099 (2.55) 7.0749 (5.52) 6.9402 (2.83) 4.1406 (0.41 ) 3.7762 (16) 3.5069 (0.43) 3.4908 (0.83) 3.4809 (1.04) 3.4683 (1.37) 3.458 (0.91 ) 3.4421 (0.4) 3.4319 (0.33) 3.3041 (98.21 ) 2.5228 (0.52) 2.5179 (0.81 ) 2.5094 (7.95) 2.505 (14.97) 2.5005 (19.67) 2.496 (13.33) 2.4916 (6.15) 2.0697 (7.08) 1 .8331 (1.06) 1.8177 (0.59) 1 .803 (1.28) 1.7953 (1.28) 1.7789 (1.07) 1.7684 (1.21 ) 1.7622 (1.22) 1 .7574 (1.23) 1.6845 (1.19) 1 .6631 (1.78) 1.63 (1.18) 1.4884 (0.37) 1.481 1 (0.45) 1.4746 (0.48) 1.4665 (0.6) 1.4626 (0.7) 1.4555 (0.97) 1.4488 (1.02) 1.4409 (0.92) 1.4309 (0.76) 1.4233 (0.91 ) 1.418 (0.89) 1.4106 (0.93) 1.3986 (0.68) 1.3889 (0.7) 1.3812 (0.7) 1.369 (1.15) 1.3571 (1.16) 1.35 (1.21 ) 1 .3392 (1.66) 1.332 (1.54) 1.3238 (1.16) 1.3124 (1.61 ) 1.3061 (1.29) 1.2971 (0.72) 1.2922 (0.68) 1.2782 (1.64) 1 .2495 (2.64) 1.2384 (1.14) 1 .226 (1.76) 1.1906 (1.08) 1.1775 (0.93) 1.1663 (1.29) 1.1595 (1.6) 1.152 (1.56) 1.1489 (1.51 ) 1.1416 (1.1 1 ) 1.1344 (1.71 ) 1.1201 (1.14) 1.1 169 (1 .17) 1.1026 (0.77) 1 .0861 (0.37) 1.0702 (0.76) 1.0593 (0.74) 1.0485 (0.73) 1.0382 (1.31 ) 1.0276 (0.75) 1.0219 (0.57) 1 .0166 (0.85) 1.0131 (1 ) 1.0033 (1 ) 0.9923 (0.89) 0.9819 (0.49) 0.9698 (1.17) 0.9636 (1.03) 0.9398 (0.97) 0.9323 (0.86) 0.9082 (0.37) 0.8369 (7.5) 0.8189 (15.5) 0.801 1 (5.59) -0.0002 (0.84)
Example 344
Solvent: DMSO-d,
7.3972 (1.36) 7.3755 (1.39) 7.1723 (2.53) 7.0376 (5.47) 6.9031 (2.8) 4.1 106 (1.1 ) 4.1019 (1 .09) 3.8658 (0.6) 3.7749 (16) 3.303 (283.9) 2.669 (0.37) 2.5391 (0.54) 2.5224 (1.13) 2.5177 (1.76) 2.509 (20.22) 2.5045 (38.92) 2.5 (52.05) 2.4955 (35.35) 2.491 (16.46) 2.3268 (0.36) 2.0694 (4.18) 1 .6614 (1 .33) 1.6491 (1.05) 1 .6352 (0.83) 1.5935 (1.5) 1.5868 (1.58) 1.5779 (1.73) 1.5699 (1.71 ) 1.5613 (1.6) 1.4814 (0.8) 1.4514 (2.92) 1.4367 (5.34) 1 .4104 (1.1 ) 1.4026 (0.87) 1 .3472 (0.51 ) 1.3398 (0.48) 1.3199 (1 .16) 1.3131 (1.17) 1.3015 (0.77) 1.2866 (2.86) 1.2668 (3.78) 1.2495 (5.06) 1.2351 (3.46) 1 .2327 (3.49) 1.2193 (2.16) 1.2034 (1 .77) 1.1865 (1.1 1 ) 1.1825 (1.26) 1.1656 (0.75) 1.1582 (0.71 ) 1 .1501 (0.62) 1.1438 (1.31 ) 1.1231 (1.31 ) 1.1 108 (0.8) 1.1052 (0.73) 1.0912 (0.58) 0.8754 (0.4) 0.8577 (0.89) 0.8417 (6.23) 0.833 (1 .96) 0.8244 (13.45) 0.8063 (6.1 1 ) -0.0002 (2.62)
Example 354
Solvent: DMSO-d6
7.8628 (0.34) 7.8404 (0.35) 7.1594 (0.47) 7.0241 (1.04) 6.8891 (0.53) 3.8649 (4) 3.2896 (60.33) 2.508 (5.24) 2.5035 (10.59) 2.4989 (14.32) 2.4943 (10.13) 2.4898 (4.71 ) 2.067 (0.66) 1.8013 (0.37) 1.6664 (0.38) 1.2869 (0.33) 1.2657 (0.5) 1.2542 (0.55) 1 .2328 (0.66) 1.0099 (0.8) 0.988 (0.37) 0.9807 (0.45) 0.82 (16) -0.0002 (1.46)
Example 355
Solvent: DMSO-d6
7.1667 (0.44) 7.0315 (0.98) 6.8965 (0.49) 3.8698 (3.74) 3.2879 (20.21 ) 3.2641 (0.69) 2.5081 (1 .95) 2.5035 (3.91 ) 2.4989 (5.29) 2.4944 (3.74) 2.4899 (1.74) 2.0671 (4.7) 1.4676 (0.46) 1.4465 (0.83) 1.4374 (0.74) 1.2051 (0.35) 1.1741 (0.38) 1.1272 (0.47) 1.1042 (0.34) 0.8198 (16) -0.0002 (0.38)
Example 358
Solvent: DMSO-d6
7.7273 (0.35) 7.7052 (0.36) 7.1934 (0.43) 7.0584 (0.98) 6.9236 (0.5) 3.7745 (3.05) 3.3107 (1 18.65) 2.5227 (0.64) 2.5093 (7.8) 2.5049 (14.31 ) 2.5004 (18.44) 2.496 (12.62) 2.4916 (6.04) 1.7773 (0.43) 1.6623 (0.4) 1.2665 (0.56) 1.2417 (0.71 ) 1.2167 (0.49) 1.0095 (0.83) 0.9904 (0.63) 0.9831 (0.49) 0.8194 (0.56) 0.8044 (16) -0.0002 (0.37)
Example 361
Solvent: DMSO-d,
7.6998 (0.59) 7.6774 (0.61 ) 7.1848 (0.46) 7.0497 (0.93) 6.9157 (0.48) 3.7781 (5.13) 3.6192 (0.34) 3.5954 (0.39) 3.3091 (188.57) 3.3066 (192.79) 2.6695 (0.37) 2.5001 (53.35) 2.4964 (50.37) 2.3268 (0.36) 1 .8674 (0.63) 1.8455 (0.79) 1.6884 (0.64) 1.6629 (0.88) 1.6267 (0.5) 1.31 16 (0.9) 1.291 1 (0.39) 1.2761 (0.86) 1.2346 (0.34) 1.2012 (0.54) 1 .1712 (0.84) 1.1395 (0.45) 1.1 174 (0.39) 1.0878 (0.32) 0.9834 (0.43) 0.9417 (2.83) 0.9253 (2.73) 0.8605 (1 .23) 0.8332 (0.68) 0.7964 (16) 0.7768 (0.69) - 0.0002 (3.56) -0.0032 (3.32)
Example 363
Solvent: DMSO-d6
5.8221 (1.12) 3.8508 (1.53) 3.7829 (0.91 ) 3.7612 (0.76) 3.7535 (0.51 ) 3.3821 (87.87) 3.3589 (0.94) 2.5851 (6.75) 2.5808 (12.43) 2.5764 (16) 2.572 (1 1.07) 2.5678 (5.34) 1 .752 (0.39) 1.7147 (0.45) 1.6778 (0.46) 1.565 (0.35) 1.5589 (0.37) 1.5271 (0.53) 1 .5228 (0.53) 1.5038 (0.56) 1.4743 (0.51 ) 1.4322 (0.35) 1.3199 (0.59) 1 .31 17 (0.62) 1.2912 (0.52) 1 .2758 (0.45) 1.2689 (0.47) 1 .251 (0.6) 1.2417 (0.51 ) 1.2332 (0.56) 1.2272 (0.53) 1.2173 (0.52) 1.209 (0.52) 1 .1829 (0.38) 0.0755 (0.75) 0.0471 (0.8) 0.041 1 (0.5) 0.0325 (0.89) 0.0291 (0.83) 0.0266 (1.07) 0.0208 (2.71 ) 0.0135 (2.05) 0.0071 (5.2) -0.0002 (6.36) - 0.0032 (5.69) -0.0059 (5.4) -0.007 (5.33) -0.0136 (3.64) -0.0159 (3.31 ) -0.0181 (4.06) -0.0241 (4.65) - 0.0361 (2.89) -0.0427 (2.74)
Intensity of sharp signals correlates with the height of the signals in a printed example of a NMR spectrum in cm and shows the real relations of signal intensities. From broad signals several peaks or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown. The H-NMR peak lists are similar to classical H-NMR prints and contain therefore usually all peaks, which are listed at classical NMR-interpretation. Additionally they can show like classical 1 H- NMR prints signals of solvents, stereoisomers of the target compounds, which are also object of the invention, and/or peaks of impurities. To show compound signals in the delta-range of solvents and/or water the usual peaks of solvents, for example peaks of DMSO in DMSO-d6 and the peak of water are shown in our H-NMR peak lists and have usually on average a high intensity. The peaks of stereoisomers of the target compounds and/or peaks of impurities have usually on average a lower intensity than the peaks of target compounds (for example with a purity >90%). Such stereoisomers and/or impurities can be typical for the specific preparation process. Therefore their peaks can help to recognize the reproduction of our preparation process via "side-products-fingerprints". An expert, who calculates the peaks of the target compounds with known methods (MestreC, ACD-simulation, but also with empirically evaluated expectation values) can isolate the peaks of the target compounds as needed optionally using additional intensity filters. This isolation would be similar to relevant peak picking at classical H-NMR interpretation. The following examples illustrate in a non-limiting manner the preparation and efficacy of the compounds of formula (I) according to the invention.
Preparation example 1 : preparation of N-cyclopropyl-N-[2-(2,6-dichlorophenoxy)ethyl]-3-(difluoromethyl)- 5-fluoro-1-methyl-1 H-pyrazole-4-carboxamide (compound 124)
Step 1 : preparation of of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid (llla-1 ) In a 500 ml flask, 6.0 g (31 mmol) of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbaldehyde are added to 30 ml of toluene. A solution of 2.4 g (62 mmol) of sodium hydroxide in 6ml of water is added to the reaction mixture, followed by 103 ml of a 30% solution of hydrogen peroxide in water, whilst keeping the temperature below 37°C. After the end of the addition, the reaction mixture is stirred at 50°C for 7 hours. Once the reaction mixture is back to room temperature, the two phases are separated and the organic phase is extracted with 100 ml of water. The combined aqueous phases are acidified to pH 2 with aqueous hydrochloric acid. The resulting white precipitate is filtered, washed twice with 20 ml of water, and dried to yield 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid as a white solid. H NMR (400 MHz, DMSO-c/6) δ ppm : 3.78 (s, 3H); 7.12 (t, 1 H, JHF = 53.60 Hz)13.19 (s, 1 H); IR (KBr) : 1688 cm"1 (C=0); 2200-3200 cm"1 broad (hydrogen bond).
Step 2 : preparation of of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride (lllb-1 ) 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylic acid and 44.3 ml of thionyl chloride are refluxed for 5 hours. After cooling down, the reaction mixture is evaporated under vacuum to yield 3.5 g of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride as a yellow oil. H NMR (400 MHz, CHCI3-c/6) δ ppm : 3.97 (s, 3H); 7.00 (t, J = 52.01 Hz, 1 H); IR (TQ) : 1759 and 1725 cm"1 (C=0).
Step 3 : preparation of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl fluoride (lllc-1 ) To a dried solution of 4.0 g (70 mmol) of potassium fluoride in 21 ml of tetrahydrothiophene-1 , 1 -dioxide is added a solution of 5.0 g (22 mmol) of 5-chloro-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride in 15 ml of toluene at 100°C. The resulting reaction mixture is stirred at 190-200°C for 22 hours. Distillation under vacuum yields 8 g of a solution (25% molar) of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H- pyrazole-4-carbonyl fluoride in tetrahydro-thiophene-1 , 1 -dioxide. H NMR (250 MHz, CHCI3-cf6) δ ppm : 3.87 (s, 3H); 6.79 (t, J = 53.75 Hz, 1 H); 9F NMR (250 MHz, CHCI3-c/6) δ ppm : 45.37 (s, COF); -1 17.5 (d, J = 28.2 Hz); -131 .6 (m).
Step 4 : preparation of of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxylic acid (llld-1 ) To 400 ml of a 1 N sodium hydroxyde aqueous solution, is added dropwise 67.5 g of a solution (10% molar) of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl fluoride in tetra-hydrothiophene- 1 , 1-dioxide. The temperature is kept below 20°C during the addition. After 2 hours of stirring at room temperature, the reaction mixture is carefully acidified to pH 2 with concentrated aqueous hydrochloric acid. The resulting white precipitate is filtered, washed with water, and dried to yield 6 g of 3- (difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxylic acid as a white solid. H NMR (400 MHz, DMSO-c/6) δ ppm: 3.90 (s, 3H); 7.22 (t, 1 H, JHF = 53.55Hz); 13.33 (s, 1 H). Step 5 : preparation of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride (llle-1 ) 9.1 g of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxylic acid and 75.5 ml of thionyl chloride are refluxed for 1.5 hours. After cooling down, the reaction mixture is evaporated under vacuum to yield 10 g of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride as a yellow oil. GC-MS ; observed M/z :Molecular ion : (M+ ) = 212 ; fragments : (M+ -CI) = 177 and (M+ -F) = 193.
Step 6 : preparation of N-cyclopropyl-N-[2-(2,6-dichlorophenoxy)ethyl]-3-(difluoromethyl)-5-fluoro-1- m ethyl- 1 H-pyrazole-4-carboxam ide
In a 13 ml Chemspeed™ vial is weighted 73 mg (0.726 mmol) of triethylamine. Then 3 ml of a 0.23 molar solution of N-[2-(2,6-dichlorophenoxy)ethyl]cyclopropanamine (0.594mmole) in dichloromethane is added followed by 3 ml of a 0.26 molar solution of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride (0.66mmole) in dichloromethane and stirred at ambient temperature for 15 hrs. 1 ml of water is then added and the mixture is deposited on a basic alumina cartridge (2g) and eluted twice by 8 ml of dichloromethane. The solvents are removed to yield 183 mg (64%) of pure N-cyclopropyl-N-[2-(2,6- dichlorophenoxy)ethyl]-3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carboxamide as an oil (M+H = 422).
Preparation example 2 : preparation of 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)cyclopentyl]-5-fluoro-1- methyl-1 H-pyrazole-4-carboxamide (compound 319)
Step 1 : preparation of methyl 1-(3,3-dimethylbutyl)-2-oxocyclopentanecarboxylate
1 17.0 g (846.0 mmol) of potassium carbonate are added to a solution consisting of 40.0 g (281.7 mmol) of methyl 2-oxocyclopentanecarboxylate in 160 ml of dry toluene. 93 g (563.4 mmol) of 1-bromo-3,3- dimethylbutane are then added dropwise, and the mixture is stirred at reflux for 14 hours. After the reaction has ended the mixture is cooled to room temperature and filtered off through Celite. The product is concentrated under reduced pressure and purified by column chromatography (silica gel 100-200 mesh, mobile phase: ethyl acetate 5%/petroleum ether). This gives 48 g (75% of theory) of methyl 1-(3,3- dimethylbutyl)-2-oxocyclopentanecarboxylate. Step 2 : preparation of 2-(3,3-dimethylbutyl)cyclopentanone
A solution consisting of 23.0 g (101 .7 mmol) of methyl 1-(3,3-dimethylbutyl)-2- oxocyclopentanecarboxylate in 80 ml of acetic acid and 80 ml of cone, hydrochloric acid is stirred at 90°C for 14 hours. After the reaction has ended, the mixture is cooled to room temperature and ice-water is added. The product is extracted with diethyl ether. The org. phase is washed with water, dried with sodium sulphate and concentrated under reduced pressure. The crude product is purified by column chromatography (silica gel 60-120, mobile phase: ethyl acetate 3% / petroleum ether). This gives 10 g (59% of theory) of 2-(3,3-dimethylbutyl)cyclopentanone.
Step 3 : preparation of 2-(3,3-dimethylbutyl)-N-hydroxycyclopentanimine
At 0°C, aq. sodium carbonate solution is added to a solution consisting of 20.0 g of (1 19 mmol) of 2-(3,3- dimethylbutyl)cyclopentanone and 16.5 g (238 mmol) of hydroxylamine hydrochloride in 200 ml of methanol until the pH is 8. The mixture is then stirred at 50°C for 15 hours. After the reaction has ended, the mixture is cooled to room temperature and filtered off and the product is concentrated under reduced pressure. The residue is extracted with water/diethyl ether. The org. phase is dried with sodium sulphate and concentrated under reduced pressure. This gives 20.0 g (92% of theory) of an 2-(3,3-dimethylbutyl)- N-hydroxycyclopentanimine.
Step 4 : preparation of 2-(3,3-dimethylbutyl)cyclopentanamine hydrochloride (1 :1 )
3.0 g of Raney nickel are added to a solution consisting of 1 .00 g (5.4 mmol) of 2-(3,3-dimethylbutyl)-N- hydroxycyclopentanimine in 10 ml of methanolic ammonia solution, and the mixture is hydrogenated with hydrogen at 20°C for 18 hours. After the reaction has ended, the mixture is filtered off and the product is concentrated under reduced pressure. The residue is dissolved in diethyl ether, and HCI gas is added. Decanting and washing with diethyl ether gives 0.5 g (45% of theory) of 2-(3,3- dimethylbutyl)cyclopentanamine hydrochloride (1 :1 ).
Step 5 : preparation of 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)cyclopentyl]-5-fluoro-1-methyl-1 H- pyrazole-4-carboxamide
As for example 1 - step 6, condensation of 1.03 g 2-(3,3-dimethylbutyl)cyclopentanamine hydrochloride over 1.06 g of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride gives 0.6 (31 % of theory) of a syn + anti mixture of 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)cyclopentyl]-5-fluoro-1-methyl- 1 H-pyrazole-4-carboxamide. logP = 4.22 (isomer A) and logP = 4.28 (isomer B).
Preparation example 3 : preparation of 3-(difluoromethyl)-N-[3-(3,3-dimethylbutyl)cyclohexyl]-5-fluoro-1- methyl-1 H-pyrazole-4-carboxamide (compound 324)
Step 1 : 3-(3,3-dimethylbut-1-yn-1-yl)aniline
1.05 g (1.5 mmol) of bis(triphenylphosphine)palladium(ll) chloride and 0.26 g (1.5 mmol) of copper(l) iodide are added to a solution consisting of 5.47 g (25 mmol) of 3-iodoaniline in 40 ml of triethylamine.
With ice-cooling, 3.08 g (37.5 mmol) of 3,3-dimethyl-1-butyne are added dropwise such that the temperature remains at 20°C. After the addition has ended, the mixture is stirred at 20°C for 20 hours.
The reaction solution is concentrated under reduced pressure and the residue formed is stirred into 1 I of water. The mixture is then extracted three times with diethyl ether. The combined organic phases are once more washed with water, dried with sodium sulphate and concentrated under reduced pressure.
The crude product obtained is purified by silica gel chromatography (mobile phase methylene chloride).
This gives 2.70 g (60% of theory) of 3-(3,3-dimethylbut-1-yn-1-yl)aniline having a content of 97% according to HPLC. logP = 2.71.
Step 2 : 3-(3,3-dimethylbutyl)cyclohexanamine
0.5 g of Ru/C 5% is added to a solution consisting of 1.04 g (0.6 mol) of 3-(3,3-dimethylbut-1-yn-1- yl)aniline in 20 ml of tetrahydrofuran, and the mixture is hydrogenated with 100 bar of hydrogen at 120°C for 40 hours. After cooling to room temperature, the catalyst is filtered off through kieselguhr and the product is concentrated under reduced pressure. This gives 0.9 g (81 % of theory) of 3-(3,3- dimethylbutyl)cyclohexanamine as main component according to MSD-HPLC. Step 3 : preparation of 3-(difluoromethyl)-N-[3-(3,3-dimethylbutyl)cyclohexyl]-5-fluoro-1-methyl-1 H- py razo le-4-carboxa m id e
As for example 1 - step 6, condensation of 0.50 g 3-(3,3-dimethylbutyl)cyclohexanamine over 0.638 g of 3-(difluoromethyl)-5-fluoro-1-methyl-1 H-pyrazole-4-carbonyl chloride gives 0.65 (54% of theory) of 3- (difluoromethyl)-N-[3-(3,3-dimethylbutyl)cyclohexyl]-5-fluoro-1-methyl-1 H-pyrazole-4-carboxamide. logP = 4.80.
General preparation example 4 : thionation of amide of formula (I) on Chemspeed™ apparatus
In a 13 ml Chemspeed™ vial is weighted 0.27mmole of phosphorous pentasulfide (P2S5). 3 ml of a 0.18 molar solution of the amide (I) (0.54mmole) in dioxane is added and the mixture is heated at reflux for two hours. The temperature is then cooled to 80°C and 2.5 ml of water are added. The mixture is heated at 80°C for one more hour. 2 ml of water are then added and the reaction mixture is extracted twice by 4 ml of dichloromethane. The organic phase is deposited on a basic alumina cartridge (2g) and eluted twice by 8 ml of dichloromethane. The solvents are removed and the crude thioamide derivative is analyzed by LCMS and NMR. Insufficiently pure compounds are further purified by preparative LCMS.
Example A : in vivo preventive test on Sphaerotheca fuliginea (cucumber)
Solvent: 49 parts by weight of N,N-dimethylformamide
Emulsifier: 1 part by weight of Alkylarylpolyglycolether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. One day after this treatment, the plants are inoculated with an aqueous spore suspension of Sphaerotheca fuliginea. Then the plants are placed in a greenhouse at approximately 23°C and a relative atmospheric humidity of approximately 70 %.
The test is evaluated 7 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table A : Table A :
Figure imgf000095_0001
Under the same conditions, total protection is observed at a dose of 500 ppm of active ingredient with compound 240, whereas poor protection (less than 25%) is observed with the des-fluoro analogue compound CMP1 as in table A2..
Table A2:
Figure imgf000095_0002
The des-fluoro analogue compound CMP1 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N- [(2-phenylcyclohexyl)methyl]-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Under the same conditions, total protection is observed at a dose of 500 ppm of active ingredient with compound 256, whereas poor protection (less than 15%) is observed with the des-fluoro analogues compound CMP2 and compound CMP3 as in table A3. Table A3:
Figure imgf000096_0001
The des-fluoro analogue compound CMP2 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-(3- phenylcyclohexyl)-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP3 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-(3-phenylcyclohexyl)-1 H-pyrazole-4- carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Under the same conditions, total protection is observed at a dose of 500 ppm of active ingredient with compound 374, whereas no protection is observed with the des-fluoro analogues compound CMP4 and compound CMP5 as in table A4.
Table A4:
Figure imgf000096_0002
The des-fluoro analogue compound CMP4 corresponds to N-[1 , 1 '-bi(cyclohexyl)-2-yl]-5-fluoro-1 ,3- dimethyl-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP5 corresponds to N- [1 , 1 '-bi(cyclohexyl)-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Example B : in vivo preventive test on Altemaria solani (tomato)
Solvent: 49 parts by weight of N,N-dimethylformamide
Emulsifier: 1 part by weight of Alkylarylpolyglycolether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. One day after this treatment, the plants are inoculated with an aqueous spore suspension of Altemaria solani. The plants remain for one day in an incubation cabinet at approximately 22°C and a relative atmospheric humidity of 100%. Then the plants are placed in an incubation cabinet at approximately 20°C and a relative atmospheric humidity of 96 %. The test is evaluated 7 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table B :
Example Efficacy Example Efficacy Example Efficacy
5 80 128 95 195 95
6 95 129 100 196 95
9 90 130 95 210 70
10 90 131 95 213 100
1 1 95 132 100 214 80
12 95 136 80 215 95
13 90 137 95 218 90
14 90 142 100 219 95
16 90 143 100 220 95
17 95 144 100 221 100
19 95 145 70 222 90
21 90 148 95 224 70
22 95 149 90 225 95
29 80 150 80 240 100
32 95 151 90 241 100
33 95 154 100 242 100
34 90 156 80 243 100
36 70 157 80 244 100
37 80 158 80 245 90
38 80 159 90 256 93
40 95 163 100 259 90
42 70 164 95 287 95
44 100 165 90 288 100
45 95 166 100 289 95
46 100 167 100 290 95
47 80 168 90 291 100
48 90 169 90 294 95
63 100 170 90 295 100
66 95 171 95 296 80
67 70 172 100 297 100
69 80 173 90 298 100
70 95 174 100 299 95
71 95 175 95 300 90
74 95 176 80 301 100
81 90 177 100 302 95
82 95 178 95 303 80
83 95 180 90 306 100
84 95 181 100 307 100
89 80 182 95 309 100
1 15 90 183 95 310 100
1 16 90 184 90 31 1 100
121 90 188 100 312 95
122 100 189 90 313 80
123 95 190 90 314 95
124 95 191 95 315 100
125 95 192 95 316 90
126 90 193 95 318 90
Table B : 127 90 194 70 319 100 Table B (next) :
Figure imgf000099_0001
Under the same conditions, high protection (at least 90%) is observed at a dose of 500 ppm of active ingredient with compound 13 and compound 14, whereas poor protection (less than 10%) is observed with the des-halogeno analogue compound CMP6 as in table B2.
Table B2:
Figure imgf000099_0002
The des-halogeno analogue compound CMP6 corresponds to 3-(difluoromethyl)-1-methyl-N-(1- phenoxypropan-2-yl)-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Under the same conditions, excellent protection (at least 95%) is observed at a dose of 500 ppm and 100 ppm of active ingredient with compound 349, whereas moderate protection (less than 60%) is observed with the des-fluoro analogue compound CMP7 as in table B3. Table B3:
Figure imgf000099_0003
The des-fluoro analogue compound CMP7 corresponds to N-(2-tert-butylcyclohexyl)-3-(difluoromethyl)-1- m ethyl- 1 H-pyrazole-4-carboxam ide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds. Example C : in vivo preventive test on Pyrenophora teres (barley)
Solvent: 49 parts by weight of N,N-dimethylformamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. One day after this treatment, the plants are inoculated with an aqueous spore suspension of Pyrenophora teres. The plants remain for 48 hours in an incubation cabinet at 22°C and a relative atmospheric humidity of 100 %. Then the plants are placed in a greenhouse at a temperature of approximately 20°C and a relative atmospheric humidity of approximately 80 %.
The test is evaluated 7-9 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table C :
Table C
Example Efficacy Example Efficacy Example Efficacy
6 70 137 89 202 80
9 100 139 90 210 90
10 95 141 90 213 100
1 1 100 142 95 214 100
12 100 143 100 215 100
13 94 144 100 216 100
14 95 145 70 217 100
16 90 147 100 218 100
19 89 148 95 219 100
21 80 149 95 220 100
28 90 150 100 221 95
29 100 151 94 222 90
32 70 153 100 240 100
33 95 154 100 241 100
35 70 155 100 242 100
36 100 156 95 243 100
37 100 157 100 244 95
38 80 158 95 245 78
40 80 161 100 247 100
42 94 162 95 256 100
43 89 163 100 258 89
46 100 164 100 259 78
62 80 165 100 260 70
63 100 166 100 271 95
66 100 167 80 287 100
67 100 168 100 288 100
68 80 171 100 289 100
70 100 172 100 290 100
71 100 173 78 291 100
83 95 174 95 294 95
84 95 175 95 295 100
89 100 176 95 296 100
1 15 100 177 100 297 100
1 16 100 178 100 298 100
1 17 78 179 100 299 100
121 100 180 100 300 100
122 100 181 100 301 100
123 100 182 100 302 100
124 90 183 100 303 100
125 100 184 100 306 100
126 100 187 100 307 100
127 100 188 100 309 100
128 100 189 100 310 100
129 100 190 95 31 1 100
130 95 191 100 312 100
131 100 192 100 313 100
132 100 193 94 314 100
135 90 195 95 315 100
136 95 196 100 316 100 Table C (next) :
Figure imgf000102_0001
Under the same conditions, total protection is observed at a dose of 500 ppm and 100 ppm of active ingredient with compound 326, whereas poor protection (less than 10%) to no protection is observed with the des-halogeno analogue compound CMP8 as in table C2.
Table C2:
Figure imgf000102_0002
The des-fluoro analogue compound CMP8 corresponds to N-(2-hexylcyclohexyl)-1-methyl-3- (trifluoromethyl)-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Example D : in vivo preventive test on Venturia inaepualis (apple scab)
Solvent: 24.5 parts by weight of acetone
24.5 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. After the spray coating has dried on, the plants are inoculated with an aqueous conidia suspension of the causal agent of apple scab (Venturia inaequalis) and then remain for 1 day in an incubation cabinet at approximately 20°C and a relative atmospheric humidity of 100 %.
The plants are then placed in a greenhouse at approximately 21 °C and a relative atmospheric humidity of approximately 90 %. The test is evaluated 10 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 100 ppm of active ingredient with the following compounds from table D :
Table D :
Figure imgf000103_0001
Example E : in vivo preventive test on Septoria tritici (wheat)
Solvent: 49 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound or active compound combination at the stated rate of application.
After the spray coating has been dried, the plants are sprayed with a spore suspension of Septoria tritici. The plants remain for 48 hours in an incubation cabinet at approximately 20°C and a relative atmospheric humidity of approximately 100 % and afterwards for 60 hours at approximately 15°C in a translucent incubation cabinet at a relative atmospheric humidity of approximately 100 %.
The plants are placed in the greenhouse at a temperature of approximately 15°C and a relative atmospheric humidity of approximately 80 %.
The test is evaluated 21 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table E : Table E
Figure imgf000104_0001
Example F : in vivo preventive test on Blumeria graminis (barley)
Solvent: 49 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound or active compound combination at the stated rate of application.
After the spray coating has been dried, the plants are dusted with spores of Blumeria graminis f.sp. hordei.
The plants are placed in the greenhouse at a temperature of approximately 18°C and a relative atmospheric humidity of approximately 80 % to promote the development of mildew pustules.
The test is evaluated 7 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table F :
Table F
Figure imgf000105_0001
Example G : in vivo preventive test on Fusarium nivale (wheat)
Solvent: 49 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound or active compound combination at the stated rate of application.
After the spray coating has been dried, the plants are slightly injured by using a sandblast and afterwards they are sprayed with a conidia suspension of Fusarium nivale (var. majus).
The plants are placed in the greenhouse under a translucent incubation cabinet at a temperature of approximately 10°C and a relative atmospheric humidity of approximately 100 %.
The test is evaluated 5 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table G :
Table G :
Example Efficacy Example Efficacy Example Efficacy
9 100 315 100 339 100
184 100 319 100 343 100
213 93 324 100 344 100
215 71 326 92 353 100
216 93 329 100 354 100
217 100 330 100 355 100
218 100 331 100 357 100
240 71 333 100 358 100
256 100 334 93 359 100
306 100 335 86 360 86
31 1 100 338 100 Example H : in vivo preventive test on Fusarium graminearum (barley)
Solvent: 49 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound or active compound combination at the stated rate of application.
After the spray coating has been dried, the plants are slightly injured by using a sandblast and afterwards they are sprayed with a conidia suspension of Fusarium graminearum.
The plants are placed in the greenhouse under a translucent incubation cabinet at a temperature of approximately 22°C and a relative atmospheric humidity of approximately 100 %.
The test is evaluated 5 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, high (at least 85 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table H :
Table H :
Figure imgf000106_0001
Example I : in vivo preventive test on Leptosphaeria nodorum (wheat)
Solvent: 49 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with a preparation of active compound at the stated rate of application. One day after this treatment, the plants are inoculated with an aqueous spore suspension of Leptosphaeria nodorum. The plants remain for 48 hours in an incubation cabinet at 22°C and a relative atmospheric humidity of 100 %. Then the plants are placed in a greenhouse at a temperature of approximately 22°C and a relative atmospheric humidity of approximately 90 %.
The test is evaluated 7-9 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100% means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table I : Table I
Figure imgf000107_0001
Under the same conditions, hioh protection (at least 90%) is observed at a dose of 500 ppm of active ingredient with compound 220 and compound 221 , whereas poor protection (less than 10%) is observed with the compound of example E-12 disclosed in patent application WO-2008/101976 as in table I2.
Table I2:
Figure imgf000107_0002
Example E-12 disclosed in international patent WO-2008/101976 corresponds to N-cyclopropyl-5-fluoro-
1 ,3-dimethyl-N-{4-[2-(trifluoromethyl)phenyl]butan-2-yl}-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds disclosed in WO-2008/101976.
Example J : in vivo preventive test on Uromyces appendiculatus (beans)
Solvent: 24.5 parts by weight of acetone
24.5 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. After the spray coating has dried on, the plants are inoculated with an aqueous spore suspension of the causal agent of bean rust (Uromyces appendiculatus) and then remain for 1 day in an incubation cabinet at approximately 20°C and a relative atmospheric humidity of 100 %.
The plants are then placed in a greenhouse at approximately 21 °C and a relative atmospheric humidity of approximately 90 %.
The test is evaluated 10 days after the inoculation. 0% means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 70 %) to total protection is observed at a dose of 100 ppm of active ingredient with the following compounds from table J : Table J
Figure imgf000108_0001
Example K : in vivo preventive test on Puccinia triticina (wheat)
Solvent: 49 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound or active compound combination is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound or active compound combination at the stated rate of application. After the spray coating has been dried, the plants are sprayed with a spore suspension of Puccinia triticina. The plants remain for 48 hours in an incubation cabinet at approximately 20°C and a relative atmospheric humidity of approximately 100 %.
The plants are placed in the greenhouse at a temperature of approximately 20°C and a relative atmospheric humidity of approximately 80 %.
The test is evaluated 8 days after the inoculation. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, good (at least 75 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table K : Table K
Figure imgf000109_0001
Under the same conditions, moderate protection (at least 70%) is observed at a dose of 500 ppm of active ingredient with compound 129 and compound 130, whereas no protection is observed with the compound of example E-13 disclosed in patent application WO-2008/101976 as in table K2.
Table K2:
Figure imgf000109_0002
Example E-13 disclosed in international patent WO-2008/101976 corresponds to N-cyclopropyl-N-[4-(3,4- dichlorophenyl)butan-2-yl]-5-fluoro-1 ,3-dimethyl-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds disclosed in WO-2008/101976.
Under the same conditions, excellent protection (at least 95%) is observed at a dose of 500 ppm of active ingredient with compound 187, whereas weak protection (less than 30%) is observed with the compound of example 18 disclosed in patent application WO-2010/012795 as in table K3. Table K3:
Example dose (ppm) Efficacy
187 from this invention 500 95
18 from WO-2010/012795 500 30 Example 18 disclosed in international patent WO-2010/012795 corresponds to N-cyclopropyl-N-[1-(2,4- dichlorophenoxy)propan-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds disclosed in WO-2010/012795.
Under the same conditions, total protection to good protection (at least 80%) is observed at a dose of 500 ppm and 100 ppm of active ingredient with compound 243, whereas moderate protection (less than 60%) to no protection is observed with the compound of example 16 disclosed in patent application WO-2010/094666 as in table K4.
Table K4:
Figure imgf000110_0001
Example 16 disclosed in international patent WO-2010/094666 corresponds to N-(2-benzylcyclohexyl)-N- cyclopropyl-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds disclosed in WO-2010/012795.
Under the same conditions, excellent protection (at least 95%) is observed at a dose of 500 ppm of active ingredient with compound 256, whereas no protection is observed with the des-fluoro analogues compound CMP2 and compound CMP3 as in table K5.
Table K5:
Figure imgf000110_0002
The des-fluoro analogue compound CMP2 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-(3- phenylcyclohexyl)-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP3 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-(3-phenylcyclohexyl)-1 H-pyrazole-4- carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Under the same conditions, total protection is observed at a dose of 500 ppm of active ingredient with compound 374, whereas no protection is observed with the des-fluoro analogues compound CMP4 and compound CMP5 as in table K6. Table K6:
Figure imgf000111_0001
The des-fluoro analogue compound CMP4 corresponds to N-[1 , 1 '-bi(cyclohexyl)-2-yl]-5-fluoro-1 ,3- dimethyl-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP5 corresponds to N- [1 , 1 '-bi(cyclohexyl)-2-yl]-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Example L : in vivo preventive test on Botrytis cinerea (beans)
Solvent: 24.5 parts by weight of acetone
24.5 parts by weight of N,N-dimethylacetamide
Emulsifier: 1 part by weight of alkylaryl polyglycol ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound. After the spray coating has dried on, 2 small pieces of agar covered with growth of Botrytis cinerea are placed on each leaf. The inoculated plants are placed in a darkened chamber at 20°C and a relative atmospheric humidity of 100 %.
2 days after the inoculation, the size of the lesions on the leaves is evaluated. 0 % means an efficacy which corresponds to that of the untreated control, while an efficacy of 100 % means that no disease is observed. Under these conditions, good (at least 70 %) to total protection is observed at a dose of 500 ppm of active ingredient with the following compounds from table L :
Table L :
Figure imgf000111_0002
Under the same conditions, excellent protection (at least 95%) is observed at a dose of 500 ppm of active ingredient with compound 240, whereas poor protection (less than 15%) is observed with the des-fluoro analogues compound CMP1 and compound CMP9 as in table L2. Table L2:
Figure imgf000112_0001
The des-fluoro analogue compound CMP1 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N- [(2-phenylcyclohexyl)methyl]-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP9 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-[(2-phenylcyclohexyl)methyl]-1 H-pyrazole-4- carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Under the same conditions, high protection (at least 90%) is observed at a dose of 500 ppm of active ingredient with compound 243, whereas poor protection (less than 30%) is observed with the compound of example 16 disclosed in patent application WO-2010/094666 as in table L3. Table L3:
Figure imgf000112_0002
Example 16 disclosed in international patent WO-2010/094666 corresponds to N-(2-benzylcyclohexyl)-N- cyclopropyl-3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds disclosed in WO-2010/012795.
Under the same conditions, good protection (at least 85%) is observed at a dose of 500 ppm of active ingredient with compound 244, whereas poor protection (less than 30%) is observed with the des-fluoro analogue compound CMP10 as in table L4.
Table L4:
Figure imgf000112_0003
The des-fluoro analogue compound CMP10 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-(2- phenoxycyclohexyl)-1 H-pyrazole-4-carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.. Under the same conditions, high protection (at least 90%) is observed at a dose of 500 ppm of active ingredient with compound 256, whereas poor protection (less than 5%) is observed with the des-fluoro analogues compound CMP2 and compound CMP3 as in table L5. Table L5:
Figure imgf000113_0001
The des-fluoro analogue compound CMP2 corresponds to N-cyclopropyl-5-fluoro-1 ,3-dimethyl-N-(3- phenylcyclohexyl)-1 H-pyrazole-4-carboxamide and the des-fluoro analogue compound CMP3 corresponds to N-cyclopropyl-3-(difluoromethyl)-1-methyl-N-(3-phenylcyclohexyl)-1 H-pyrazole-4- carboxamide.
These results show that the compounds according to the invention have a much better biological activity than the structurally closest compounds.
Example M : in vivo protective test on Cochliobolus miyabeanus (rice)
Solvent: 28.5 parts by weight of acetone
Emulsifier: 1.5 part by weight of polyoxyethylene alkyl phenyl ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated rate of application. One day after spraying, the plants are inoculated with an aqueous spore suspension of the causal agent of rice brown spot (Cochliobolus miyabeanus). The plants are then placed in an incubator at approximately 25°C and a relative atmospheric humidity of approximately 100 % for 1 day.
The test is evaluated 4 days after the inoculation. 0 % means an efficacy which corresponds to that of the control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, high (at least 85 %) protection is observed at a dose of 250 ppm of active ingredient with the following compounds from table M :
Table M :
Example Efficacy Example Efficacy Example Efficacy
215 98 315 97 339 92
216 90 324 97 344 95
217 98 329 98 357 93
306 95 330 85 360 94
31 1 97 338 96 Example N : in vivo protective test on Phakopsora pachyrhizi (soybeans)
Solvent: 28.5 parts by weight of acetone
Emulsifier: 1.5 part by weight of polyoxyethylene alkyl phenyl ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated rate of application. One day after spraying, the plants are inoculated with an aqueous spore suspension of the causal agent of soybean rust (Phakopsora pachyrhizi). The plants are then placed in a greenhouse at approximately 20°C and a relative atmospheric humidity of approximately 80 %.
The test is evaluated 1 1 days after the inoculation. 0% means an efficacy which corresponds to that of the control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, high (at least 85 %) to total protection is observed at a dose of 250 ppm of active ingredient with the following compounds from table M :
Table N :
Figure imgf000114_0001
Example O : in vivo protective test on Pyricularia oryzae (rice)
Solvent: 28.5 parts by weight of acetone
Emulsifier: 1.5 part by weight of polyoxyethylene alkyl phenyl ether
To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for preventive activity, young plants are sprayed with the preparation of active compound at the stated rate of application. One day after spraying, the plants are inoculated with an aqueous spore suspension of the causal agent of rice blast (Pyricularia oryzae). The plants are then placed in an incubator at approximately 25°C and a relative atmospheric humidity of approximately 100 % for 1 day. The test is evaluated 5 days after the inoculation. 0 % means an efficacy which corresponds to that of the control, while an efficacy of 100 % means that no disease is observed.
Under these conditions, high (at least 80 %) to total protection is observed at a dose of 250 ppm of active ingredient with the following compounds from table O : Table O :
Figure imgf000115_0001
Example P : inhibition of aflatoxines produced by Aspergillus parasiticus
Compounds were tested in microtiter plates (96 well black flat and transparent bottom) in Aflatoxin- inducing liquid media (20g sucrose, yeast extract 4g, KH2P04 1g, and MgS04 7H20 0.5g per liter), supplemented with 20mM of Cavasol (hydroxypropyl-beta-cyclodextrin) and containing 1 % of DMSO. The assay is started by inoculating the medium with a concentrated spore suspension of Aspergillus parasiticus at a final concentration of 1000 spores/ml.
The plate was covered and incubated at 20°C for 7 days.
After 7 days of culture, OD measurement at OD62onm with multiple read per well (circle: 4 x 4) was taken with an Infinite 1000 (Tecan) to calculate the growth inhibition. In the same time bottom fluorescence measurement at Em360nm and Ex426nm with multiple read per well (square: 3 x 3) was taken to calculate inhibition of aflatoxin formation.
Compounds from table O show good (at least 80%) to total inhibition of aflatoxines production at 50 μΜ. Growth inhibition of Fusarium graminearum of these examples vary from 67 to 100 % at 50 μΜ.
Table P
% Inhibition of % Inhibition of % Inhibition of % Inhibition of
Example Aflatoxin at 50 fungal growth at Example Aflatoxin at 50 fungal growth at μΜ 50 μΜ μΜ 50 μΜ
70 97 78 189 100 94
71 100 83 190 88 77
76 100 83 191 100 100
77 100 98 192 100 91
78 83 65 193 100 92
79 100 93 196 100 91
81 97 80 202 100 84
82 100 100 213 100 100
89 100 89 214 100 93
116 100 82 215 100 100
117 99 81 216 100 100
119 95 77 217 100 100
120 100 100 219 81 71
121 100 98 221 100 100
122 100 91 222 91 78
123 100 96 225 100 85
124 99 81 240 100 98
125 96 76 241 100 97
126 100 89 242 100 100
128 83 71 243 100 100
129 100 100 244 99 82
132 100 85 247 93 78
134 100 79 255 100 90
136 93 71 256 96 79
142 100 84 259 97 82
143 96 73 288 100 99
144 100 94 290 82 72
148 90 67 291 100 100
150 100 82 292 100 86
151 100 100 293 100 100
153 100 99 294 100 84
154 100 100 295 100 100
155 100 100 297 100 85
162 100 100 298 100 100
163 100 100 301 100 100
165 99 83 302 100 100
166 100 88 303 100 90
169 100 84 306 100 100
172 100 100 307 100 92
173 100 85 309 100 82
174 85 67 310 100 96
175 100 92 311 100 97
178 100 88 312 100 99
180 100 100 313 99 82
182 100 90 315 100 100
183 82 79 316 100 100
184 100 100 317 100 90
185 100 89 318 100 89
187 100 100 319 100 89 Table P (next) :
% Inhibition of % Inhibition of % Inhibition of % Inhibition of
Example Aflatoxin at 50 fungal growth at Example Aflatoxin at 50 fungal growth at μΜ 50 μΜ μΜ 50 μΜ
320 99 82 343 100 87
322 100 99 344 100 89
328 100 91 350 100 100
329 100 97 351 100 100
330 100 87 352 99 85
331 99 79 353 99 85
333 100 92 359 100 90
334 100 90 360 100 96
335 100 84 361 100 84
338 100 100 364 99 81
339 100 100 367 100 100
340 100 95 368 100 93

Claims

Figure imgf000118_0001
wherein
• X1 and X2 which can be the same or different, represent a halogen atom ;
• Y represents a Ci-C4-alkyl ;
• T represents O or S ;
• Q represents CR R2 ; -CR3=CR4- ; -CR3=N-0- ; or -C(=W)- ;
• Q2, Q3 and Q4 , which can be the same or different, represent a direct bond ; CR R2 ; -CR3=CR4- ;
-C≡C- ; -CR3=N-0- ; -0-N=CR3- ; O ; S ; SO ; S02 ; NR5 ; SiR6R7 ; or -C(=U)-;
• B represents a phenyl ring that can be susbtituted by up to 5 groups X which can be the same or different ; a naphthyl ring that can be susbtituted by up to 7 groups X which can be the same or different ; a saturated, partially saturated or unsaturated, monocyclic or fused bicyclic 4-, 5-, 6-, 7- , 8-, 9-, 10-membered ring comprising from 1 up to 4 heteroaroms selected in the list consisting of N, O, S, that can be substituted by up to 6 groups X which can be the same or different ; a hydrogen atom ; a halogen atom ; a substituted or non-substituted Ci-Ci2-alkyl group ; a C1-C12- halogenoalkyl group having 1 to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C8-cycloalkyl group ; a substituted or non-substituted C3-C8-cycloalkenyl group, a bicyclo[2.2.1]heptan-2-yl group ; a tri(Ci-C8-alkyl)silyl group ; a substituted or non- substituted C2-C12 alkenyl group ; or a substituted or non-substituted C2-Ci2 alkynyl group ;
• X represents a halogen atom ; nitro ; cyano ; isonitrile ; hydroxy ; amino ; sulfanyl ; pentafluoro-λ6- sulfanyl ; formyl ; formyloxy ; formylamino ; substituted or non-substituted (hydroxyimino)-Ci-C8- alkyl ; substituted or non-substituted (Ci-C8-alkoxyimino)-Ci-C8-alkyl ; substituted or non- substituted (C2-C8-alkenyloxyimino)-Ci-C8-alkyl ; substituted or non-substituted (C2-C8- alkynyloxyimino)-Ci-C8-alkyl ; substituted or non-substituted (benzyloxyimino)-Ci-C8-alkyl ; carboxy ; carbamoyl ; N-hydroxycarbamoyl ; carbamate ; substituted or non-substituted Ci-C8- alkyl ; Ci-C8-halogenoalkyl having 1 to 5 halogen atoms ; substituted or non-substituted C2-C8- alkenyl ; C2-C8-halogenoalkenyl having 1 to 5 halogen atoms ; substituted or non-substituted C2- C8-alkynyl ; C2-C8-halogenoalkynyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkoxy ; Ci-C8-halogenoalkoxy having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylsulfanyl ; Ci-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylsulfinyl ; Ci-C8-halogenoalkylsulfinyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylsulfonyl ; Ci-C8-halogenoalkylsulfonyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylamino ; substituted or non-substituted di-C-i-Cs-alkylamino ; substituted or non-substituted C2-C8-alkenyloxy ; C2-C8-halogenoalkenyloxy having 1 to 5 halogen atoms ; substituted or non-substituted C3-C8-alkynyloxy ; C2-C8- halogenoalkynyloxy having 1 to 5 halogen atoms ; substituted or non-substituted C3-C7-cycloalkyl ; C3-C7-halogenocycloalkyl having 1 to 5 halogen atoms ; substituted or non-substituted (C3-C7- cycloalkyl)-Ci-C8-alkyl ; substituted or non-substituted (C3-C7-cycloalkyl)-C2-C8-alkenyl ; substituted or non-substituted (C3-C7-cycloalkyl)-C2-C8-alkynyl ; substituted or non-substituted tri(Ci-C8-alkyl)silyl ; substituted or non-substituted tri(Ci-C8-alkyl)silyl-Ci-C8-alkyl ; substituted or non-substituted Ci-C8-alkylcarbonyl ; Ci-C8-halogenoalkylcarbonyl having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylcarbonyloxy ; Ci-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylcarbonylamino ; Ci-C8- halogenoalkyl- carbonylamino having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8- alkoxycarbonyl ; Ci-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms ; substituted or non- substituted Ci-C8-alkyloxycarbonyloxy ; Ci-C8-halogenoalkoxycarbonyloxy having 1 to 5 halogen atoms ; substituted or non-substituted Ci-C8-alkylcarbamoyl ; substituted or non-substituted di-C-r C8-alkylcarbamoyl ; substituted or non-substituted Ci-C8-alkylaminocarbonyloxy ; substituted or non-substituted di-Ci-C8-alkylaminocarbonyloxy ; substituted or non-substituted N-(Ci-C8- alkyl)hydroxy carbamoyl ; substituted or non-substituted Ci-C8-alkoxycarbamoyl ; substituted or non-substituted N-(Ci-C8-alkyl)-Ci-C8-alkoxycarbamoyl ; aryl that can be susbtituted by up to 6 groups Q which can be the same or different ; Ci-C8-arylalkyl that can be susbtituted by up to 6 groups Q which can be the same or different ; C2-C8-arylalkenyl that can be susbtituted by up to 6 groups Q which can be the same or different ; C2-C8-arylalkynyl that can be susbtituted by up to 6 groups Q which can be the same or different ; aryloxy that can be susbtituted by up to 6 groups Q which can be the same or different ; arylsulfanyl that can be susbtituted by up to 6 groups Q which can be the same or different ; arylamino that can be susbtituted by up to 6 groups Q which can be the same or different ; Ci-C8-arylalkyloxy that can be susbtituted by up to 6 groups Q which can be the same or different ; Ci-C8-arylalkylsulfanyl that can be susbtituted by up to 6 groups Q which can be the same or different ; or Ci-C8-arylalkylamino that can be susbtituted by up to 6 groups Q which can be the same or different ; or
• two substituent X together with the consecutive carbon atoms to which they are linked can form a 5- or 6-membered, saturated carbocycle or saturated heterocycle, which can be substituted by up to four groups Q which can be the same or different ;
• Z represents a hydrogen atom ; a formyl group ; a substituted or non-substituted Ci-C8-alkyl ; a substituted or non substituted Ci-C8-alkoxy ; a non-substituted C3-C7-cycloalkyl or a C3-C7- cycloalkyl substituted by up to 10 atoms or groups that can be the same or different and that can be selected in the list consisting of halogen atoms, cyano, Ci-C8-alkyl, Ci-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, Ci-C8-alkoxy, Ci-C8- halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, Ci-C8- alkoxycarbonyl, Ci-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that can be the same or different, Ci-C8-alkylaminocarbonyl and di-Ci-C8-alkylaminocarbonyl ; • R and R2 independently represent a hydrogen atom ; a halogen atom ; cyano ; substituted or non-substituted Ci-Ci2-alkyl ; substituted or non-substituted C2-Ci2-alkenyl ; substituted or non- substituted C2-Ci2-alkynyl ; substituted or non-substituted C3-C7-cycloalkyl ; Ci-Ci2-halogenoalkyl having 1 to 5 halogen atoms ; substituted or non-substituted C-rC8-alkoxy ; substituted or non- substituted Ci-C8-alkylsulfanyl ; substituted or non-substituted Ci-C8-alkylamino ; substituted or non-substituted di-(Ci-C8-alkyl)amino ; or substituted or non-substituted Ci-C8-alkoxycarbonyl ; or R and R2 are a C2-C5-alkylene group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl or Ci-C2-halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ; or
• The R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form a 3-, 4-, 5-, -6 or 7-membered saturated carbocycle that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl or Ci-C2-halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ; or
• The R substituent of the group Q' and the R substituent of the group Ql+2, i being an integer between 1 and 2, together with the consecutive carbon atoms to which they are linked can form a 3-, 4-, 5-, 6- or 7-membered saturated carbocycle that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl or Ci-C2-halogenoalkyl comprising up to 5 halogen atoms that can be the same or different ;
• R3 and R4 independently represent a hydrogen atom ; substituted or non-substituted Ci-C8-alkyl ; substituted or non-substituted C2-C8-alkenyl ; substituted or non-substituted C2-C8-alkynyl ; substituted or non-substituted C3-C7-cycloalkyl ; or Ci-C8-halogenoalkyl having 1 to 5 halogen atoms ; R5 represents a hydrogen atom ; a substituted or non-substituted Ci-C8-alkyl ; a Ci-C8- halogenoalkyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C2-C8-alkenyl ; a C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C8-alkynyl ; a C3-C8- halogenoalkynyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C7-cycloalkyl ; a C3-C7-halogeno-cycloalkyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted C3-C7- cycloalkyl-Ci-C8-alkyl ; formyl ; a substituted or non-substituted Ci-C8-alkylcarbonyl ; Ci-C8- halogenoalkylcarbonyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted Ci-C8-alkoxycarbonyl ; Ci-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that can be the same or different ; a substituted or non-substituted Ci-C8- alkylsulphonyl ; Ci-C8-halogenoalkylsulphonyl comprising up to 9 halogen atoms that can be the same or different ; phenylmethylene that can be substituted by up to 7 groups Q which can be the same or different ; or phenylsulphonyl that can be substituted by up to 5 groups Q which can be the same or different ;
• R6 and R7 independently represent a substituted or non-substituted Ci-C8-alkyl ;
• W represents O ; or S ;
• U represents O ; S ; N-ORa ; or N-CN ; • Ra represents a hydrogen atom ; a substituted or non-substituted Ci-C4-alkyl ; or a C1-C4- halogenoalkyl comprising up to 7 halogen atoms that can be the same or different ;
• Q independently represents a halogen atom ; cyano ; nitro ; substituted or non-substituted C-|-C8- alkyl ; Ci-C8-halogenoalkyl having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted C-rC8-alkoxy ; Ci-C8-halogenoalkoxy having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C8-alkylsulfanyl ; Ci-C8- halogenoalkylsulfanyl having 1 to 9 halogen atoms that can be the same or different ; substituted or non-substituted tri(Ci-C8)alkylsilyl ; substituted or non-substituted tri(Ci-C8)alkylsilyl-Ci-C8-alkyl ; substituted or non-substituted (Ci-C8-alkoxyimino)-Ci-C8-alkyl ; substituted or non-substituted (benzyloxyimino)-Ci-C8-alkyl ;
with the provisio that -Q -Q2-Q3-Q4- does not represent CR R2 when B represents a substituted or non- substituted phenyl, naphthyl or 2-pyridyl ring ;
or that -Q -Q2-Q3-Q4- does not represent [CR R2]2 or CR R2-C(=W)- or a cycloalkyl-1 ,2-diyl group, when B represents a substituted or non-substituted phenyl, naphthyl or heterocyclic ring ;
or that Z does not represent a hydrogen atom when -Q -Q2- represents a unsubstituted cyclohexyl-1 ,2- diyl group and -Q3-Q4- represents a substituted or non-substituted cyclopropyl-1 ,2-diyl group ;
as well as its salts, N-oxydes, metallic complexes, metalloidic complexes and optically active isomers.
2. A compound according to claim 1 wherein X1 and X2 independently represent a chlorine or a fluorine atom.
3. A compound according to claim 1 or 2 wherein Y represents methyl.
4. A compound according to anyone of claims 1 to 3 wherein T represents O.
5. A compound according to anyone of claims 1 to 4 wherein B represents a substituted or non- substituted phenyl ring ; a substituted or non-substituted naphthyl ring ; a substituted or non-substituted pyridyl ring ; a substituted or non-substituted thienyl ring ; or a substituted or non-substituted
benzothienyl ring; preferably a substituted or non-substituted phenyl ring or a substituted or non- substituted 2-pyridyl ring.
6. A compound according to anyone of claims 1 to 5 wherein X independently represents a halogen atom; substituted or non-substituted Ci-C8-alkyl ; Ci-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different ; substituted or non-substituted tri(Ci-C8-alkyl)silyl ; substituted or non- substituted Ci-C8-alkoxy or Ci-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different ; substituted or non-substituted Ci-C8-alkylsulfanyl or Ci-C8-halogenoalkylsulfanyl comprising up to 9 halogen atoms that can be the same or different ; or wherein two consecutive substituents X together with the phenyl ring form a substituted or non-substituted cyclopentyl or cyclohexyl ring.
7. A compound according to anyone of claims 1 to 6 wherein X independently represents fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, terbutyl, cyclopropyl, cyclopentyl, cyclohexyl, trimethylsilyl, methoxy, ethoxy, methylsulfanyl, ethylsulfanyl, trifluoromethyl, trichloromethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy,
difluoromethysulfanyl, trifluoromethylsulfanyl and difluorochloro-methylsulfanyl
8. A compound according to anyone of claims 1 to 7 wherein Z represents a hydrogen atom ; a non- substituted C3-C7 cycloalkyl ; or a C3-C7 cycloalkyl substituted by up to 10 groups or atoms that can be the same or different and that can be selected in the list consisting of halogen atoms, Ci-C8-alkyl, C-|-C8- halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C-rC8-alkoxy and d- C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different; preferably a non- substituted C3-C7-cycloalkyl; more preferably a cyclopropyl.
9. A compound according to anyone of claims 1 to 8 wherein wherein Q represents CR R2
10. A compound according to anyone of claims 1 to 9 wherein Q2, Q3 and Q4, which can be the same or different, represents a direct bond ; CR R2 ; or O.
1 1. A compound according to anyone of claims 1 to 10 wherein Q2 represents CR R2, Q3 represents a direct bond or O, and Q4 represent a direct bond.
12. A compound according to anyone of claims 1 to 1 1 wherein R and R2 independently represent a hydrogen atom, a fluorine atom, a substituted or non-substituted Ci-C8-alkyl or a substituted or non- substituted Ci-C8-alkoxy
13. A compound according to anyone of claims 1 to 1 1 wherein the R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form an optionally mono or polysubstituted 3-, 4-, 5-, 6- or 7- membered saturated carbocycle; preferably an optionally mono or polysubstituted cyclopropyl, cyclopentyl, cyclohexyl or a cycloheptyl ring; more preferably a cyclopropyl, a cyclopentyl or a cyclohexyl ring.
14. A compound according to claim 13 wherein the R substituent of the group Q' and the R substituent of the group Ql+ , i being an integer between 1 and 3, together with the consecutive carbon atoms to which they are linked can form a cyclopentyl, cyclohexyl or cycloheptyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl
15. A compound according to claim 14 wherein
• -Q -Q2- represents an optionally mono or polysubstituted cyclopentyl-1 ,2-diyl, cyclohexyl- 1 ,2-diyl or cycloheptyl- 1 ,2-diyl group; and • -Q3-Q4-B represents a bicyclo[2.2.1]heptan-2-yl group, A1, A2, A3 or wherein
Figure imgf000123_0001
o A represents , wherein
Ra represents hydrogen, Ci-C4-alkyl or Ci-C4-haloalkyl ;
Z represents -CRa2Ra3Ra4 or -Si Ra2Ra3Ra4 ;
s represents 0, 1 , 2 or 3 ;
t represents 0 or 1 ;
Ra2, Ra3, Ra4 independently of one another represent hydrogen, halogen Ci-C4-alkyl or C1-C4- haloalkyl ; or
Ra3 aanndd RRaa4 together with the carbon atom to which they are attached form an optionally substituted saturated or insaturated 3- to 6-membered carbocyclic ring
Figure imgf000123_0002
o A2 represents , wherein
Ra6 represent hydrogen, halogen, Ci-C8-alkyl or Ci-C8-haloalkyl ;
R , R , R independently of one another represent hydrogen, methyl or ethyl
o
Figure imgf000123_0003
, wherein
Ra9 represent hydrogen or fluorine ;
o A4 represents
Figure imgf000123_0004
, wherein
Ra ° represent optionally substituted C2-Ci2-alkyl, optionally substituted C2-Ci2-alkenyl, optionally substituted C2-Ci2-alkynyl, optionally substituted C3-C8-cycloalkyl, optionally substituted phenyl or heterocyclyl;
Ra 1 represent hydrogen or halogen ; and
Ra 2 represent hydrogen or halogen.
16. A compound according to claim 15 wherein
Ra represents hydrogen or methyl ;
s represents 0 or 1 ;
Ra2 represents chlorine, methyl, ethyl, isopropyl or trifluoromethyl;
Ra3 represents chlorine, methyl, ethyl, isopropyl or trifluoromethyl; Ra4 represents hydrogen, chlorine, methyl, ethyl, isopropyl or trifluoromethyl; Ra5 represents hydrogen or methyl ;
Ra6 represents hydrogen ;
Ra7 represents hydrogen or methyl ;
Ra8 represents fluorine, chlorine, methyl, ethyl or trifluoromethyl ;
Ra9 represent hydrogen or fluorine;
Ra ° represents ethyl, propyl, isopropyl, butyl, secbutyl, terbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, omethylcyclopropyl, 4-fluorophenyl, 4-bromophenyl, 2-thienyl, 3-thienyl or 2-fury;
Ra 1 represents hydrogen ;
Ra 2 represents hydrogen.
17. A compound according to anyone of claims 1 to 1 1 wherein the R substituent of the group Q' and the R substituent of the group Ql+2, i being an integer between 1 and 2, together with the consecutive carbon atoms to which they are linked can form an cyclohexyl group that can be substituted by up to four groups that can be the same or different and that can be selected in the list consisting of fluorine, chlorine, methyl, ethyl, propyl, isopropyl, isobutyl, secbutyl, terbutyl, trifluoromethyl or difluoromethyl
18. A compound according to claim 17 wherein -Q -Q2-Q3- represents an optionally mono or polysubstituted cyclohexyl-1 ,3-diyl and -Q4-B represents a bicyclo[2.2.1 ]heptan-2-yl group, A1 , A2, A3 or
A4 group as defined in claim 15 or 16.
19. A compound according to anyone of claims 1 to 18 wherein R3 and R4 independently represent a hydrogen atom, or a substituted or non-substituted Ci-C8-alkyl.
20. A compound according to anyone of claims 1 to 19 wherein R5 represents a substituted or non- substituted Ci-C8-alkyl.
21. A compound according to anyone of claims 1 to 20 wherein R6 and R7 independently represent a non- substituted Ci-C8-alkyl, preferably a non-substituted Ci-C3-alkyl, more preferably methyl.
22. A compound according to anyone of claims 1 to 21 wherein U represents O or N-0-(Ci-C4-alkyl).
23. A fungicide composition comprising, as an active ingredient, an effective amount of a compound of formula (I) according to claims 1 to 24 and an agriculturally acceptable support, carrier or filler.
24. A method for controlling phytopathogenic fungi of crops, characterized in that an agronomically effective and substantially non-phytotoxic quantity of a compound according to claims 1 to 22 or a composition according to claim 23 is applied to the soil where plants grow or are capable of growing, to the leaves and/or the fruit of plants or to the seeds of plants.
PCT/EP2011/059026 2010-06-03 2011-06-01 N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues WO2011151370A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AU2011260333A AU2011260333B2 (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues
CA2796194A CA2796194A1 (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues
US13/700,716 US8999956B2 (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)] pyrazole(thio)carboxamides and their heterosubstituted analogues
KR1020127031072A KR20130088022A (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl] pyrazole(thio)carboxamides and their heterosubstituted analogues
PL11723939T PL2576517T3 (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)]pyrazole (thio)carboxamides and their heterosubstituted analogues
BR112012030607-3A BR112012030607B1 (en) 2010-06-03 2011-06-01 COMPOUND, FUNGICIDE COMPOSITION AND METHOD FOR CONTROLING PHYTOPATHOGENIC CROPS FUNGI
ES11723939.2T ES2532971T3 (en) 2010-06-03 2011-06-01 N - [(het) arylalkyl)] pyrazole (thio) carboxamides and their hetero substituted analogs
EP11723939.2A EP2576517B1 (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)]pyrazole (thio)carboxamides and their heterosubstituted analogues
CN201180027220.8A CN102918028B (en) 2010-06-03 2011-06-01 N-[(mixing) arylalkyl] pyrazoles (sulfo-) carboxylic acid amides and the assorted analogue replaced thereof
MX2012013896A MX2012013896A (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues.
UAA201214917A UA107231C2 (en) 2010-06-03 2011-06-01 N - [(het) arylalkyl] pyrazole (thio) carboxamides and their heterosubstituted analogs
JP2013512887A JP5730993B2 (en) 2010-06-03 2011-06-01 N-[(Heta) arylalkyl)] pyrazole (thio) carboxamides and their hetero-substituted analogues

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP10356020.7 2010-06-03
EP10356020 2010-06-03
US36800310P 2010-07-27 2010-07-27
US61/368,003 2010-07-27
EP10356032.2 2010-11-15
EP10356032 2010-11-15

Publications (1)

Publication Number Publication Date
WO2011151370A1 true WO2011151370A1 (en) 2011-12-08

Family

ID=45066204

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2011/059026 WO2011151370A1 (en) 2010-06-03 2011-06-01 N-[(het)arylalkyl)] pyrazole (thio)carboxamides and their heterosubstituted analogues

Country Status (15)

Country Link
US (1) US8999956B2 (en)
EP (1) EP2576517B1 (en)
JP (1) JP5730993B2 (en)
KR (1) KR20130088022A (en)
CN (1) CN102918028B (en)
AR (1) AR081834A1 (en)
AU (1) AU2011260333B2 (en)
BR (1) BR112012030607B1 (en)
CA (1) CA2796194A1 (en)
CL (1) CL2012003358A1 (en)
CO (1) CO6660480A2 (en)
ES (1) ES2532971T3 (en)
MX (1) MX2012013896A (en)
PL (1) PL2576517T3 (en)
WO (1) WO2011151370A1 (en)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013079566A3 (en) * 2011-11-30 2013-07-25 Bayer Intellectual Property Gmbh Fungicidal n- bicycloalkyl and n-tricycloalkyl pyrazole - 4 - (thio) carboxamide derivatives
WO2013167651A1 (en) * 2012-05-11 2013-11-14 Syngenta Participations Ag Crop enhancement
WO2014010737A1 (en) 2012-07-12 2014-01-16 日産化学工業株式会社 Oxime-substituted amide compound and pest control agent
EP2730570A1 (en) * 2012-11-13 2014-05-14 Bayer CropScience AG Pyridyloxyal alkyl carboxamides and their use as endoparasiticides and nematicide
WO2014206954A1 (en) * 2013-06-26 2014-12-31 Bayer Cropscience Ag N-cycloalkyl-n-[(fusedphenyl)methylene]-(thio)carboxamide derivatives
US9132129B2 (en) 2010-11-15 2015-09-15 Katholieke Universiteit Leuven Antiviral compounds
WO2015144657A1 (en) * 2014-03-27 2015-10-01 Bayer Cropscience Ag Use of pyridyloxyalkylcarboxamides for the control of unwanted microorganisms
US9232799B2 (en) 2010-06-03 2016-01-12 Bayer Intellectual Property Gmbh N-[(het)arylethyl)] pyrazole(thio)carboxamides and their heterosubstituted analogues
US9320276B2 (en) 2010-11-02 2016-04-26 Bayer Intellectual Property Gmbh N-hetarylmethyl pyrazolylcarboxamides
US9499563B2 (en) 2009-05-15 2016-11-22 Katholieke Universiteit Leuven Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors
US9556205B2 (en) 2010-06-03 2017-01-31 Bayer Intellectual Property Gmbh Fungicide N-[(trisubstitutedsilyl)methyl]-carboxamide derivatives
US9617220B2 (en) 2012-08-07 2017-04-11 Bayer Cropscience Ag Method for the preparation of perfluoroalkyl containing pyrazoles carboxylates
US10029986B2 (en) 2014-02-18 2018-07-24 Nissan Chemical Industries, Ltd. Alkynyl pyridine-substituted amide compound and pesticide
EP3189043B1 (en) * 2014-09-03 2020-11-18 C4x Discovery Limited Therapeutic compounds as inhibitors of the orexin-1 receptor

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104649972B (en) * 2013-11-25 2017-09-15 沈阳中化农药化工研发有限公司 A kind of pyrazol acid amide compounds and purposes
CN110615764A (en) * 2019-10-25 2019-12-27 浙江工业大学 N- (2-benzamide) -1H-pyrazole-4-formamide compound and preparation method and application thereof
CN110669007A (en) * 2019-10-25 2020-01-10 浙江工业大学 3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxylic ester compound and preparation method and application thereof
CN110615765B (en) * 2019-10-25 2021-06-25 浙江工业大学 (1H-pyrazole-4-formamido) ethyl benzoate compound and preparation method and application thereof
CN110713458B (en) * 2019-10-25 2021-06-29 浙江工业大学 N- (2-benzoylaminoethyl) -2-chloronicotinamide compound and preparation method and application thereof
CN110734403B (en) * 2019-10-25 2021-08-31 浙江工业大学 (S) -2- (1H-pyrazole-4-formamido) propyl benzoate compound and preparation method and application thereof
CN113845480B (en) * 2020-09-30 2023-05-12 江苏中旗科技股份有限公司 Protenamide compound and application thereof, bactericide and application thereof

Citations (214)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2036008A (en) 1934-11-07 1936-03-31 White Martin Henry Plug fuse
US3247908A (en) 1962-08-27 1966-04-26 Robook Nicolay Nikolaevich Adjustable blades hydraulic turbine runner
US4761373A (en) 1984-03-06 1988-08-02 Molecular Genetics, Inc. Herbicide resistance in plants
WO1989010396A1 (en) 1988-04-28 1989-11-02 Plant Genetic Systems N.V. Plants with modified stamen cells
EP0407798A2 (en) 1989-07-08 1991-01-16 Bayer Ag Process for the preparation of aqueous polyurethane dispersions.
EP0407762A1 (en) 1989-06-28 1991-01-16 Hoechst Aktiengesellschaft Degradable polymer blends
WO1991002069A1 (en) 1989-08-10 1991-02-21 Plant Genetic Systems N.V. Plants with modified flowers
US5013659A (en) 1987-07-27 1991-05-07 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
US5084082A (en) 1988-09-22 1992-01-28 E. I. Du Pont De Nemours And Company Soybean plants with dominant selectable trait for herbicide resistance
WO1992005251A1 (en) 1990-09-21 1992-04-02 Institut National De La Recherche Agronomique Dna sequence imparting cytoplasmic male sterility, mitochondrial genome, nuclear genome, mitochondria and plant containing said sequence and process for the preparation of hybrids
US5198599A (en) 1990-06-05 1993-03-30 Idaho Resarch Foundation, Inc. Sulfonylurea herbicide resistance in plants
EP0559320A2 (en) 1992-02-29 1993-09-08 Tioxide Specialties Limited Water-in-oil emulsions
EP0571427A1 (en) 1991-02-13 1993-12-01 Hoechst Schering AgrEvo GmbH Plasmids containing dna-sequences that cause changes in the carbohydrate concentration and the carbohydrate composition in plants, as well as plant cells and plants containing these plasmids
US5273894A (en) 1986-08-23 1993-12-28 Hoechst Aktiengesellschaft Phosphinothricin-resistance gene, and its use
US5276268A (en) 1986-08-23 1994-01-04 Hoechst Aktiengesellschaft Phosphinothricin-resistance gene, and its use
WO1994004693A2 (en) 1992-08-26 1994-03-03 Zeneca Limited Novel plants and processes for obtaining them
US5304732A (en) 1984-03-06 1994-04-19 Mgi Pharma, Inc. Herbicide resistance in plants
WO1994009144A1 (en) 1992-10-14 1994-04-28 Zeneca Limited Novel plants and processes for obtaining them
WO1994011520A2 (en) 1992-11-09 1994-05-26 Zeneca Limited Novel plants and processes for obtaining them
EP0600983A1 (en) 1991-08-05 1994-06-15 Bio Tech Resources A fermentation process for producing natamycin.
US5331107A (en) 1984-03-06 1994-07-19 Mgi Pharma, Inc. Herbicide resistance in plants
EP0607730A1 (en) 1992-12-24 1994-07-27 International Business Machines Corporation Method of direct transferring of electrically conductive elements into a substrate
EP0609013A2 (en) 1993-01-21 1994-08-03 Matsushita Electric Industrial Co., Ltd. Recording and reproducing apparatus
EP0609022A2 (en) 1993-01-25 1994-08-03 Matsushita Electric Industrial Co., Ltd. Image encoding apparatus
WO1994021795A1 (en) 1993-03-25 1994-09-29 Ciba-Geigy Ag Novel pesticidal proteins and strains
US5378824A (en) 1986-08-26 1995-01-03 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
WO1995004826A1 (en) 1993-08-09 1995-02-16 Institut Für Genbiologische Forschung Berlin Gmbh Debranching enzymes and dna sequences coding them, suitable for changing the degree of branching of amylopectin starch in plants
US5402608A (en) 1992-02-27 1995-04-04 Chu; Rey-Chin Prefabricated built-up building construction
WO1995009910A1 (en) 1993-10-01 1995-04-13 Mitsubishi Corporation Gene that identifies sterile plant cytoplasm and process for preparing hybrid plant by using the same
US5434283A (en) 1990-04-04 1995-07-18 Pioneer Hi-Bred International, Inc. Edible endogenous vegetable oil extracted from rapeseeds of reduced stearic and palmitic saturated fatty acid content
EP0663956A1 (en) 1992-08-12 1995-07-26 Hoechst Schering AgrEvo GmbH Dna sequences which lead to the formation of polyfructans (levans), plasmids containing these sequences as well as a process for preparing transgenic plants
WO1995026407A1 (en) 1994-03-25 1995-10-05 National Starch And Chemical Investment Holding Corporation Method for producing altered starch from potato plants
US5463175A (en) 1990-06-25 1995-10-31 Monsanto Company Glyphosate tolerant plants
WO1995031553A1 (en) 1994-05-18 1995-11-23 Institut Für Genbiologische Forschung Berlin Gmbh DNA SEQUENCES CODING FOR ENZYMES CAPABLE OF FACILITATING THE SYNTHESIS OF LINEAR α-1,4 GLUCANS IN PLANTS, FUNGI AND MICROORGANISMS
WO1995035026A1 (en) 1994-06-21 1995-12-28 Zeneca Limited Novel plants and processes for obtaining them
WO1996001904A1 (en) 1994-07-08 1996-01-25 Stichting Scheikundig Onderzoek In Nederland Production of oligosaccharides in transgenic plants
EP0709000A1 (en) 1993-07-15 1996-05-01 Siemens Ag Method and device for firing an m-pulse d.c./a.c. converter assembly consisting of a master d.c./a.c. converter and at least one slave d.c./a.c. converter
WO1996015248A1 (en) 1994-11-10 1996-05-23 Hoechst Schering Agrevo Gmbh Dna molecules that code for enzymes involved in starch synthesis, vectors, bacteria, transgenic plant cells and plants containing said molecules
WO1996019581A1 (en) 1994-12-22 1996-06-27 Hoechst Schering Agrevo Gmbh Dna molecules coding for debranching enzymes derived from plants
EP0719338A1 (en) 1993-09-09 1996-07-03 Hoechst Schering AgrEvo GmbH Combination of dna sequences which enable the formation of modified starch in plant cells and plants, processes for the production of these plants and the modified starch obtainable therefrom
WO1996021023A1 (en) 1995-01-06 1996-07-11 Centrum Voor Plantenveredelings- En Reproduktieonderzoek (Cpro - Dlo) Dna sequences encoding carbohydrate polymer synthesizing enzymes and method for producing transgenic plants
EP0728213A1 (en) 1993-11-09 1996-08-28 E.I. Du Pont De Nemours And Company Transgenic fructan accumulating crops and methods for their production
WO1996027674A1 (en) 1995-03-08 1996-09-12 Hoechst Schering Agrevo Gmbh Modified starch from plants, plants synthesizing this starch, and process for its preparation
US5561236A (en) 1986-03-11 1996-10-01 Plant Genetic Systems Genetically engineered plant cells and plants exhibiting resistance to glutamine synthetase inhibitors, DNA fragments and recombinants for use in the production of said cells and plants
WO1996033270A1 (en) 1995-04-20 1996-10-24 American Cyanamid Company Structure-based designed herbicide resistant products
WO1996034968A2 (en) 1995-05-05 1996-11-07 National Starch And Chemical Investment Holding Corporation Improvements in or relating to plant starch composition
WO1996038567A2 (en) 1995-06-02 1996-12-05 Rhone-Poulenc Agrochimie Dna sequence of a gene of hydroxy-phenyl pyruvate dioxygenase and production of plants containing a gene of hydroxy-phenyl pyruvate dioxygenase and which are tolerant to certain herbicides
US5605011A (en) 1986-08-26 1997-02-25 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
WO1997011188A1 (en) 1995-09-19 1997-03-27 Planttec Biotechnologie Gmbh Plants which synthesise a modified starch, process for the production thereof and modified starch
US5637489A (en) 1986-08-23 1997-06-10 Hoechst Aktiengesellschaft Phosphinothricin-resistance gene, and its use
WO1997020936A1 (en) 1995-12-06 1997-06-12 Zeneca Limited Modification of starch synthesis in plants
WO1997026362A1 (en) 1996-01-16 1997-07-24 Planttec Biotechnologie Gmbh Nucleic acid molecules from plants coding enzymes which participate in the starch synthesis
WO1997032985A1 (en) 1996-03-07 1997-09-12 Planttec Biotechnologie Gmbh Forschung & Entwicklung Nucleic acid molecules coding for debranching enzymes from maize
WO1997041218A1 (en) 1996-04-29 1997-11-06 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Herbicide resistant rice
WO1997042328A1 (en) 1996-05-06 1997-11-13 Planttec Biotechnologie Gmbh Nucleic acid molecules which code the potato debranching enzyme
EP0807551A2 (en) 1996-05-16 1997-11-19 Britax (Geco) S.A. Exterior mirror for a vehicle
WO1997044472A1 (en) 1996-05-17 1997-11-27 Planttec Biotechnologie Gmbh Nucleic acid molecules coding soluble maize starch synthases
WO1997045545A1 (en) 1996-05-29 1997-12-04 Hoechst Schering Agrevo Gmbh Nucleic acid molecules encoding enzymes from wheat which are involved in starch synthesis
WO1997047808A1 (en) 1996-06-12 1997-12-18 Pioneer Hi-Bred International, Inc. Substitutes for modified starch in paper manufacture
WO1997047806A1 (en) 1996-06-12 1997-12-18 Pioneer Hi-Bred International, Inc. Substitutes for modified starch in paper manufacture
WO1997047807A1 (en) 1996-06-12 1997-12-18 Pioneer Hi-Bred International, Inc. Substitutes for modified starch in paper manufacture
WO1998000549A1 (en) 1996-06-27 1998-01-08 The Australian National University MANIPULATION OF CELLULOSE AND/OR β-1,4-GLUCAN
US5712107A (en) 1995-06-07 1998-01-27 Pioneer Hi-Bred International, Inc. Substitutes for modified starch and latexes in paper manufacture
WO1998003486A1 (en) 1996-07-24 1998-01-29 Bayer Aktiengesellschaft 1,3-dimethyl-5-fluoro-pyrazole-4-carboxamide derivatives, their preparation and their use as microbicides
US5731180A (en) 1991-07-31 1998-03-24 American Cyanamid Company Imidazolinone resistant AHAS mutants
US5739082A (en) 1990-02-02 1998-04-14 Hoechst Schering Agrevo Gmbh Method of improving the yield of herbicide-resistant crop plants
EP0837944A2 (en) 1995-07-19 1998-04-29 Rhone-Poulenc Agrochimie Mutated 5-enol pyruvylshikimate-3-phosphate synthase, gene coding for said protein and transformed plants containing said gene
WO1998020145A2 (en) 1996-11-05 1998-05-14 National Starch And Chemical Investment Holding Corporation Improvements in or relating to starch content of plants
WO1998022604A1 (en) 1996-11-20 1998-05-28 Pioneer Hi-Bred International, Inc. Methods of producing high-oil seed by modification of starch levels
WO1998027212A1 (en) 1996-12-19 1998-06-25 Planttec Biotechnologie Gmbh Novel nucleic acid molecules from maize and their use for the production of modified starch
US5773702A (en) 1996-07-17 1998-06-30 Board Of Trustees Operating Michigan State University Imidazolinone herbicide resistant sugar beet plants
WO1998027806A1 (en) 1996-12-24 1998-07-02 Pioneer Hi-Bred International, Inc. Oilseed brassica containing an improved fertility restorer gene for ogura cytoplasmic male sterility
WO1998032326A2 (en) 1997-01-24 1998-07-30 Pioneer Hi-Bred International, Inc. Methods for $i(agrobacterium)-mediated transformation
WO1998039460A1 (en) 1997-03-04 1998-09-11 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Nucleic acid molecules from artichoke ($i(cynara scolymus)) encoding enzymes having fructosyl polymerase activity
WO1998040503A1 (en) 1997-03-10 1998-09-17 Planttec Biotechnologie Gmbh Nucleic acid molecules encoding starch phosphorylase from maize
US5824790A (en) 1994-06-21 1998-10-20 Zeneca Limited Modification of starch synthesis in plants
US5840946A (en) 1987-12-31 1998-11-24 Pioneer Hi-Bred International, Inc. Vegetable oil extracted from rapeseeds having a genetically controlled unusually high oleic acid content
WO1999012950A2 (en) 1997-09-06 1999-03-18 National Starch And Chemical Investment Holding Corporation Improvements in or relating to stability of plant starches
WO1999024593A1 (en) 1997-11-06 1999-05-20 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Nucleic acid molecules which encode proteins having fructosyl transferase activity and methods for producing long-chain inulin
WO1999024586A1 (en) 1997-11-07 1999-05-20 Aventis Cropscience S.A. Chimeric hydroxy-phenyl pyruvate dioxygenase, dna sequence and method for obtaining plants containing such a gene, with herbicide tolerance
US5908810A (en) 1990-02-02 1999-06-01 Hoechst Schering Agrevo Gmbh Method of improving the growth of crop plants which are resistant to glutamine synthetase inhibitors
WO1999034008A1 (en) 1997-12-24 1999-07-08 Aventis Cropscience S.A. Method for enzymatic preparation of homogentisate
US5928937A (en) 1995-04-20 1999-07-27 American Cyanamid Company Structure-based designed herbicide resistant products
US5965755A (en) 1993-10-12 1999-10-12 Agrigenetics, Inc. Oil produced from the Brassica napus
US5969169A (en) 1993-04-27 1999-10-19 Cargill, Incorporated Non-hydrogenated canola oil for food applications
WO1999053072A1 (en) 1998-04-09 1999-10-21 E.I. Du Pont De Nemours And Company Starch r1 phosphorylation protein homologs
WO1999058688A2 (en) 1998-05-08 1999-11-18 Aventis Cropscience Gmbh Nucleic acid molecules which code for enzymes derived from wheat and which are involved in the synthesis of starch
WO1999058654A2 (en) 1998-05-13 1999-11-18 Planttec Biotechnologie Gmbh Forschung & Entwicklung Transgenic plants with a modified activity of a plastidial adp/atp translocator
WO1999057965A1 (en) 1998-05-14 1999-11-18 Aventis Cropscience Gmbh Sulfonylurea-tolerant sugar beet mutants
WO1999058690A2 (en) 1998-05-08 1999-11-18 Aventis Cropscience Gmbh Nucleic acid molecules which code for enzymes derived from wheat and which are involved in the synthesis of starch
WO1999066050A1 (en) 1998-06-15 1999-12-23 National Starch And Chemical Investment Holding Corporation Improvements in or relating to plants and plant products
US6013861A (en) 1989-05-26 2000-01-11 Zeneca Limited Plants and processes for obtaining them
WO2000004173A1 (en) 1998-07-17 2000-01-27 Aventis Cropscience N.V. Methods and means to modulate programmed cell death in eukaryotic cells
WO2000008185A1 (en) 1998-07-31 2000-02-17 Aventis Cropscience Gmbh Nucleic acid molecule coding for beta-amylase, plants synthesizing a modified starch, method of production and applications
WO2000008175A2 (en) 1998-07-31 2000-02-17 Aventis Cropscience Gmbh Nucleic acid module coding for alpha glucosidase, plants that synthesize modified starch, methods for the production and use of said plants, and modified starch
WO2000008184A1 (en) 1998-07-31 2000-02-17 Aventis Cropscience Gmbh Plants which synthesize a modified starch, methods for producing the plants, their use, and the modified starch
WO2000011192A2 (en) 1998-08-25 2000-03-02 Pioneer Hi-Bred International, Inc. Plant glutamine: fructose-6-phosphate amidotransferase nucleic acids
WO2000014249A1 (en) 1998-09-02 2000-03-16 Planttec Biotechnologie Gmbh Nucleic acid molecules encoding an amylosucrase
WO2000022140A1 (en) 1998-10-09 2000-04-20 Planttec Biotechnologie Gmbh Forschung & Entwicklung NUCLEIC ACID MOLECULES WHICH CODE A BRANCHING ENZYME FROM BACTERIA OF THE GENUS NEISSERIA, AND A METHOD FOR PRODUCING α-1,6-BRANCHED α-1,4-GLUCANS
US6063947A (en) 1996-07-03 2000-05-16 Cargill, Incorporated Canola oil having increased oleic acid and decreased linolenic acid content
WO2000028052A2 (en) 1998-11-09 2000-05-18 Planttec Biotechnologie Gmbh Nucleic acid molecules from rice encoding an r1 protein and their use for the production of modified starch
WO2000047727A2 (en) 1999-02-08 2000-08-17 Planttec Biotechnologie Gmbh Forschung & Entwicklung Nucleic acid molecules encoding alternansucrase
WO2000066746A1 (en) 1999-04-29 2000-11-09 Syngenta Limited Herbicide resistant plants
WO2000066747A1 (en) 1999-04-29 2000-11-09 Syngenta Limited Herbicide resistant plants
WO2000073422A1 (en) 1999-05-27 2000-12-07 Planttec Biotechnologie Gmbh Genetically modified plant cells and plants with an increased activity of an amylosucrase protein and a branching enzyme
WO2000077229A2 (en) 1999-06-11 2000-12-21 Aventis Cropscience Gmbh R1 protein from wheat and the use thereof for the production of modified strach
WO2001012782A2 (en) 1999-08-12 2001-02-22 Aventis Cropscience Gmbh Transgenically modified plant cells and plants having modified gbssi- and be-protein activity
WO2001012826A2 (en) 1999-08-11 2001-02-22 Aventis Cropscience Gmbh Nucleic acid molecules derived from plants which code for enzymes which are involved in the synthesis of starch
WO2001014569A2 (en) 1999-08-20 2001-03-01 Basf Plant Science Gmbh Increasing the polysaccharide content in plants
WO2001017333A1 (en) 1999-09-10 2001-03-15 Texas Tech University Transgenic fiber producing plants with increased expression of sucrose phosphate synthase
WO2001019975A2 (en) 1999-09-15 2001-03-22 National Starch And Chemical Investment Holding Corporation Plants having reduced activity in two or more starch-modifying enzymes
WO2001024615A1 (en) 1999-10-07 2001-04-12 Valigen (Us), Inc. Non-transgenic herbicide resistant plants
US6229072B1 (en) 1995-07-07 2001-05-08 Adventa Technology Ltd Cytoplasmic male sterility system production canola hybrids
US6270828B1 (en) 1993-11-12 2001-08-07 Cargrill Incorporated Canola variety producing a seed with reduced glucosinolates and linolenic acid yielding an oil with low sulfur, improved sensory characteristics and increased oxidative stability
US6284479B1 (en) 1995-06-07 2001-09-04 Pioneer Hi-Bred International, Inc. Substitutes for modified starch and latexes in paper manufacture
WO2001066704A2 (en) 2000-03-09 2001-09-13 Monsanto Technology Llc Methods for making plants tolerant to glyphosate and compositions thereof
WO2001065922A2 (en) 2000-03-09 2001-09-13 E. I. Du Pont De Nemours And Company Sulfonylurea-tolerant sunflower plants
US6323392B1 (en) 1999-03-01 2001-11-27 Pioneer Hi-Bred International, Inc. Formation of brassica napus F1 hybrid seeds which exhibit a highly elevated oleic acid content and a reduced linolenic acid content in the endogenously formed oil of the seeds
WO2001098509A2 (en) 2000-06-21 2001-12-27 Syngenta Participations Ag Grain processing method and transgenic plants useful therein
WO2002012172A1 (en) 2000-08-08 2002-02-14 Dow Agrosciences Llc Unsaturated oxime ethers and their use as fungicides
WO2002026995A1 (en) 2000-09-29 2002-04-04 Syngenta Limited Herbicide resistant plants
WO2002034923A2 (en) 2000-10-23 2002-05-02 Bayer Cropscience Gmbh Monocotyledon plant cells and plants which synthesise modified starch
WO2002036782A2 (en) 2000-10-30 2002-05-10 Maxygen, Inc. Novel glyphosate n-acetyltransferase (gat) genes
WO2002036787A2 (en) 2000-10-30 2002-05-10 Bayer Cropscience S.A. Herbicide-tolerant plants through bypassing metabolic pathway
WO2002045485A1 (en) 2000-12-08 2002-06-13 Commonwealth Scienctific And Industrial Research Organisation Modification of sucrose synthase gene expression in plant tissue and uses therefor
WO2002046387A2 (en) 2000-12-07 2002-06-13 Syngenta Limited Plant derived hydroxy phenyl pyruvate dioxygenases (hppd) resistant against triketone herbicides and transgenic plants containing these dioxygenases
WO2002079410A2 (en) 2001-03-30 2002-10-10 Basf Plant Science Gmbh Glucan chain length domains
WO2002101059A2 (en) 2001-06-12 2002-12-19 Bayer Cropscience Gmbh Transgenic plants synthesising high amylose starch
WO2003013226A2 (en) 2001-08-09 2003-02-20 Cibus Genetics Non-transgenic herbicide resistant plants
WO2003033540A2 (en) 2001-10-17 2003-04-24 Basf Plant Science Gmbh Starch
WO2003035617A2 (en) 2001-10-23 2003-05-01 Dow Agrosciences Llc Patent Department Derivatives of uk-2a
WO2003071860A2 (en) 2002-02-26 2003-09-04 Bayer Cropscience Gmbh Method for generating maize plants with an increased leaf starch content, and their use for making maize silage
WO2003092360A2 (en) 2002-04-30 2003-11-13 Verdia, Inc. Novel glyphosate-n-acetyltransferase (gat) genes
WO2004014138A1 (en) 2002-08-07 2004-02-19 Kumiai Chemical Industry Co., Ltd. Herbicide compositions
WO2004024928A2 (en) 2002-09-11 2004-03-25 Bayer Cropscience S.A. Transformed plants with enhanced prenylquinone biosynthesis
US6734341B2 (en) 1999-09-02 2004-05-11 Pioneer Hi-Bred International, Inc. Starch synthase polynucleotides and their use in the production of new starches
WO2004040012A2 (en) 2002-10-29 2004-05-13 Basf Plant Science Gmbh Compositions and methods for identifying plants having increased tolerance to imidazolinone herbicides
WO2004053219A2 (en) 2002-12-05 2004-06-24 Jentex Corporation Abrasive webs and methods of making the same
WO2004056999A1 (en) 2002-12-19 2004-07-08 Bayer Cropscience Gmbh Plant cells and plants which synthesize a starch with an increased final viscosity
WO2004058723A1 (en) 2002-12-24 2004-07-15 Syngenta Participations Ag Biphenyl derivatives and their use as fungicides
US6768044B1 (en) 2000-05-10 2004-07-27 Bayer Cropscience Sa Chimeric hydroxyl-phenyl pyruvate dioxygenase, DNA sequence and method for obtaining plants containing such a gene, with herbicide tolerance
WO2004078983A2 (en) 2003-03-07 2004-09-16 Basf Plant Science Gmbh Enhanced amylose production in plants
WO2004090140A2 (en) 2003-04-09 2004-10-21 Bayer Bioscience N.V. Methods and means for increasing the tolerance of plants to stress conditions
WO2004106529A2 (en) 2003-05-28 2004-12-09 Basf Aktiengesellschaft Wheat plants having increased tolerance to imidazolinone herbicides
WO2005002324A2 (en) 2003-07-04 2005-01-13 Institut National De La Recherche Agronomique Method of producing double low restorer lines of brassica napus having a good agronomic value
WO2005002359A2 (en) 2003-05-22 2005-01-13 Syngenta Participations Ag Modified starch, uses, methods for production thereof
WO2005012529A1 (en) 2003-07-31 2005-02-10 Toyo Boseki Kabushiki Kaisha Plant producing hyaluronic acid
WO2005012515A2 (en) 2003-04-29 2005-02-10 Pioneer Hi-Bred International, Inc. Novel glyphosate-n-acetyltransferase (gat) genes
WO2005017157A1 (en) 2003-08-15 2005-02-24 Commonwealth Scientific And Industrial Research Organisation (Csiro) Methods and means for altering fiber characteristics in fiber-producing plants
WO2005020673A1 (en) 2003-08-29 2005-03-10 Instituto Nacional De Technologia Agropecuaria Rice plants having increased tolerance to imidazolinone herbicides
WO2005030941A1 (en) 2003-09-30 2005-04-07 Bayer Cropscience Gmbh Plants with increased activity of a class 3 branching enzyme
WO2005030942A1 (en) 2003-09-30 2005-04-07 Bayer Cropscience Gmbh Plants with reduced activity of a class 3 branching enzyme
WO2005042474A1 (en) 2003-10-31 2005-05-12 Mitsui Chemicals, Inc. Diamine derivative, process for producing the same, and plant disease control agent containing the same as active ingredient
EP1559320A1 (en) 2002-10-31 2005-08-03 Ishihara Sangyo Kaisha, Ltd. 3-benzoyl-2,4,5-substituted pyridine derivatives or salts thereof and bactericides containing the same
WO2005070917A1 (en) 2004-01-23 2005-08-04 Sankyo Agro Company, Limited 3-(dihydro(tetrahydro)isoquinolin-1-yl)quinolines
WO2005093093A2 (en) 2004-03-22 2005-10-06 Basf Aktiengesellschaft Methods and compositions for analyzing ahasl genes
WO2005095617A2 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Plants with increased activity of a starch phosphorylating enzyme
WO2005095618A2 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Plants with reduced activity of the starch phosphorylating enzyme phosphoglucan, water dikinase
WO2005095632A2 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Methods for identifying proteins with starch phosphorylating enzymatic activity
WO2005095619A1 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Plants with increased activity of multiple starch phosphorylating enzymes
WO2005123927A1 (en) 2004-06-21 2005-12-29 Bayer Cropscience Gmbh Plants that produce amylopectin starch with novel properties
WO2006007373A2 (en) 2004-06-16 2006-01-19 Basf Plant Science Gmbh Polynucleotides encoding mature ahasl proteins for creating imidazolinone-tolerant plants
WO2006015376A2 (en) 2004-08-04 2006-02-09 Basf Plant Science Gmbh Monocot ahass sequences and methods of use
WO2006018319A1 (en) 2004-08-18 2006-02-23 Bayer Cropscience Gmbh Plants with increased plastidic activity of r3 starch-phosphorylating enzyme
WO2006021972A1 (en) 2004-08-26 2006-03-02 Dhara Vegetable Oil And Foods Company Limited A novel cytoplasmic male sterility system for brassica species and its use for hybrid seed production in indian oilseed mustard brassica juncea
WO2006024351A1 (en) 2004-07-30 2006-03-09 Basf Agrochemical Products B.V. Herbicide-resistant sunflower plants, plynucleotides encoding herbicide-resistant acetohydroxy acid synthase large subunit proteins, and methods of use
WO2006032538A1 (en) 2004-09-23 2006-03-30 Bayer Cropscience Gmbh Methods and means for producing hyaluronan
WO2006045633A1 (en) 2004-10-29 2006-05-04 Bayer Bioscience N.V. Stress tolerant cotton plants
WO2006060634A2 (en) 2004-12-01 2006-06-08 Basf Agrochemical Products, B.V. Novel mutation involved in increased tolerance to imidazolinone herbicides in plants
WO2006061215A2 (en) 2004-12-11 2006-06-15 Bayer Cropscience Ag 2-alkyl-cycloalk(en)yl-carboxamides
WO2006063862A1 (en) 2004-12-17 2006-06-22 Bayer Cropscience Ag Transformed plant expressing a dextransucrase and synthesizing a modified starch
WO2006072603A2 (en) 2005-01-10 2006-07-13 Bayer Cropscience Ag Transformed plant expressing a mutansucrase and synthesizing a modified starch
WO2006103107A1 (en) 2005-04-01 2006-10-05 Bayer Cropscience Ag Phosphorylated waxy potato starch
WO2006108702A1 (en) 2005-04-08 2006-10-19 Bayer Cropscience Ag High-phosphate starch
JP2006304779A (en) 2005-03-30 2006-11-09 Toyobo Co Ltd Plant producing hexosamine in high productivity
WO2006129204A2 (en) 2005-05-31 2006-12-07 Devgen Nv Rnai for control of insects and arachnids
WO2006133827A2 (en) 2005-06-15 2006-12-21 Bayer Bioscience N.V. Methods for increasing the resistance of plants to hypoxic conditions
WO2006136351A2 (en) 2005-06-24 2006-12-28 Bayer Bioscience N.V. Methods for altering the reactivity of plant cell walls
WO2007003961A2 (en) 2005-06-30 2007-01-11 Prosidion Limited Gpcr agonists
WO2007009823A1 (en) 2005-07-22 2007-01-25 Bayer Cropscience Ag Overexpression of starch synthase in plants
WO2007014290A2 (en) 2005-07-26 2007-02-01 E. I. Du Pont De Nemours And Company Fungicidal carboxamides
WO2007024782A2 (en) 2005-08-24 2007-03-01 Pioneer Hi-Bred International, Inc. Compositions providing tolerance to multiple herbicides and methods of use thereof
WO2007027777A2 (en) 2005-08-31 2007-03-08 Monsanto Technology Llc Nucleotide sequences encoding insecticidal proteins
WO2007035650A2 (en) 2005-09-16 2007-03-29 Monsanto Technology Llc Methods for genetic control of insect infestations in plants and compositions thereof
WO2007039315A1 (en) 2005-10-05 2007-04-12 Bayer Cropscience Ag Plants with an increased production of hyaluronan ii
WO2007039314A2 (en) 2005-10-05 2007-04-12 Bayer Cropscience Ag Plants with increased hyaluronan production
WO2007039316A1 (en) 2005-10-05 2007-04-12 Bayer Cropscience Ag Improved methods and means for producings hyaluronan
WO2007074405A2 (en) 2005-09-16 2007-07-05 Devgen Nv Dsrna as insect control agent
WO2007080126A2 (en) 2006-01-12 2007-07-19 Devgen N.V. Dsrna as insect control agent
WO2007080127A2 (en) 2006-01-12 2007-07-19 Devgen N.V. Dsrna as insect control agent
WO2007103567A2 (en) 2006-03-09 2007-09-13 E. I. Dupont De Nemours & Company Polynucleotide encoding a maize herbicide resistance gene and methods for use
WO2007107302A2 (en) 2006-03-21 2007-09-27 Bayer Bioscience N.V. Novel genes encoding insecticidal proteins
WO2007107326A1 (en) 2006-03-21 2007-09-27 Bayer Bioscience N.V. Stress resistant plants
WO2008003746A1 (en) 2006-07-06 2008-01-10 Bayer Cropscience Sa N-(4-pyridin-2-ylbutyl) carboxamide derivatives, their process of preparation and their use as fungicides
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008081017A1 (en) 2007-01-03 2008-07-10 Bayer Cropscience Ag New n-alkynylcarboxamide derivatives
WO2008101976A1 (en) 2007-02-22 2008-08-28 Bayer Cropscience Sa Fungicide n-(3-phenylpropyl)carboxamide derivatives
WO2008150473A2 (en) 2007-05-30 2008-12-11 Syngenta Participations Ag Cytochrome p450 genes conferring herbicide resistance
WO2008148570A1 (en) 2007-06-08 2008-12-11 Syngenta Participations Ag Pyrazole carboxylic acid amides useful as microbiocides
WO2009012998A1 (en) 2007-07-26 2009-01-29 Syngenta Participations Ag Novel microbiocides
WO2009068313A2 (en) 2007-11-28 2009-06-04 Bayer Bioscience N.V. Brassica plant comprising a mutant indehiscent allele
WO2009094442A2 (en) 2008-01-22 2009-07-30 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
WO2009127718A2 (en) 2008-04-18 2009-10-22 Syngenta Participations Ag Novel microbiocides
WO2009127726A1 (en) 2008-04-18 2009-10-22 Syngenta Participations Ag Novel microbiocides
WO2009127722A1 (en) 2008-04-18 2009-10-22 Syngenta Participations Ag Novel microbiocides
WO2009144079A1 (en) 2008-04-14 2009-12-03 Bayer Bioscience N.V. New mutated hydroxyphenylpyruvate dioxygenase, dna sequence and isolation of plants which are tolerant to hppd inhibitor herbicides
WO2010006732A2 (en) 2008-07-17 2010-01-21 Bayer Bioscience N.V. Brassica plant comprising a mutant indehiscent allelle
WO2010012795A1 (en) 2008-08-01 2010-02-04 Bayer Cropscience Sa Fungicidal n-(2-phenoxyethyl)carboxamide derivatives and their aza, thia and sila analogues
WO2010015681A1 (en) 2008-08-07 2010-02-11 Bayer Cropscience Sa Fungicidal n-(2-pyridylpropyl)carboxamide derivatives and their oxa, aza and thia analogues
WO2010025451A2 (en) 2008-08-29 2010-03-04 Dow Agrosciences Llc 5,8-difluoro-4-(2-(4-(heteroaryloxy)-phenyl)ethylamino)quinazolines and their use as agrochemicals
WO2010063700A2 (en) 2008-12-05 2010-06-10 Syngenta Participations Ag Novel microbiocides
WO2010094666A2 (en) 2009-02-17 2010-08-26 Bayer Cropscience Ag Fungicidal n-(phenylcycloalkyl)carboxamide, n-(benzylcycloalkyl)carboxamide and thiocarboxamide derivatives
WO2010106071A1 (en) 2009-03-18 2010-09-23 Syngenta Participations Ag N-hydroxy-l-methyl-lh-pyrazole-4-carboxamide derivatives and their use as microbiocides
WO2011045355A1 (en) 2009-10-16 2011-04-21 Syngenta Participations Ag Novel microbiocides

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7825068B2 (en) * 2005-04-08 2010-11-02 Bayer Cropscience Ag Heterocyclylethylcarboxamide derivatives
EP1772449A1 (en) * 2005-10-05 2007-04-11 Bayer CropScience S.A. New N-alkyl-heterocyclyl carboxamide derivatives
CN101415698A (en) * 2006-04-05 2009-04-22 拜尔农科股份有限公司 Fungicide n-cyclopropyl-sulfonylamide derivatives
KR101538811B1 (en) * 2007-04-03 2015-07-22 이 아이 듀폰 디 네모아 앤드 캄파니 substituted benzene fungicides
EP2019481A1 (en) * 2007-07-25 2009-01-28 Danmarks Tekniske Universitet Switch-mode DC-DC converter with multiple power transformers
CL2008002241A1 (en) * 2007-07-31 2009-12-28 Bayer Cropscience Sa N-substituted 6-membered fused (hetero) aryl-methylene-n-cycloalkyl carboxamide derivatives; fungicidal composition comprising one of said compounds; and method for the control of phytopathogenic fungi of agricultural crops.
RU2480457C2 (en) 2007-07-31 2013-04-27 Байер Кропсайенс Аг Fungicial n-cycloalkylbenzyl thiocarboxamides or n-cycloalkylbenzyl-n'-substituted amidine derivatives
BRPI0811335B1 (en) * 2007-07-31 2018-06-19 Bayer Intellectual Property Gmbh Compound, fungicidal composition comprising the same and method for the control of plant pathogenic fungi
AR076839A1 (en) * 2009-05-15 2011-07-13 Bayer Cropscience Ag FUNGICIDE DERIVATIVES OF PIRAZOL CARBOXAMIDAS
EP2576516B1 (en) 2010-06-03 2014-12-17 Bayer Intellectual Property GmbH N-[(het)arylethyl)]pyrazole(thio)carboxamides and their heterosubstituted analogues
UA110703C2 (en) 2010-06-03 2016-02-10 Байєр Кропсайнс Аг Fungicidal n-[(trisubstitutedsilyl)methyl]carboxamide

Patent Citations (226)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2036008A (en) 1934-11-07 1936-03-31 White Martin Henry Plug fuse
US3247908A (en) 1962-08-27 1966-04-26 Robook Nicolay Nikolaevich Adjustable blades hydraulic turbine runner
US4761373A (en) 1984-03-06 1988-08-02 Molecular Genetics, Inc. Herbicide resistance in plants
US5331107A (en) 1984-03-06 1994-07-19 Mgi Pharma, Inc. Herbicide resistance in plants
US5304732A (en) 1984-03-06 1994-04-19 Mgi Pharma, Inc. Herbicide resistance in plants
US5646024A (en) 1986-03-11 1997-07-08 Plant Genetic Systems, N.V. Genetically engineered plant cells and plants exhibiting resistance to glutamine synthetase inhibitors, DNA fragments and recombinants for use in the production of said cells and plants
US7112665B1 (en) 1986-03-11 2006-09-26 Bayer Bioscience N.V. Genetically engineered plant cells and plants exhibiting resistance to glutamine synthetase inhibitors, DNA fragments and recombinants for use in the production of said cells and plants
US5561236A (en) 1986-03-11 1996-10-01 Plant Genetic Systems Genetically engineered plant cells and plants exhibiting resistance to glutamine synthetase inhibitors, DNA fragments and recombinants for use in the production of said cells and plants
US5648477A (en) 1986-03-11 1997-07-15 Plant Genetic Systems, N.V. Genetically engineered plant cells and plants exhibiting resistance to glutamine synthetase inhibitors, DNA fragments and recombinants for use in the production of said cells and plants
US5273894A (en) 1986-08-23 1993-12-28 Hoechst Aktiengesellschaft Phosphinothricin-resistance gene, and its use
US5637489A (en) 1986-08-23 1997-06-10 Hoechst Aktiengesellschaft Phosphinothricin-resistance gene, and its use
US5276268A (en) 1986-08-23 1994-01-04 Hoechst Aktiengesellschaft Phosphinothricin-resistance gene, and its use
US5378824A (en) 1986-08-26 1995-01-03 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
US5605011A (en) 1986-08-26 1997-02-25 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
US5141870A (en) 1987-07-27 1992-08-25 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
US5013659A (en) 1987-07-27 1991-05-07 E. I. Du Pont De Nemours And Company Nucleic acid fragment encoding herbicide resistant plant acetolactate synthase
US5840946A (en) 1987-12-31 1998-11-24 Pioneer Hi-Bred International, Inc. Vegetable oil extracted from rapeseeds having a genetically controlled unusually high oleic acid content
WO1989010396A1 (en) 1988-04-28 1989-11-02 Plant Genetic Systems N.V. Plants with modified stamen cells
US5084082A (en) 1988-09-22 1992-01-28 E. I. Du Pont De Nemours And Company Soybean plants with dominant selectable trait for herbicide resistance
US6013861A (en) 1989-05-26 2000-01-11 Zeneca Limited Plants and processes for obtaining them
EP0407762A1 (en) 1989-06-28 1991-01-16 Hoechst Aktiengesellschaft Degradable polymer blends
EP0407798A2 (en) 1989-07-08 1991-01-16 Bayer Ag Process for the preparation of aqueous polyurethane dispersions.
WO1991002069A1 (en) 1989-08-10 1991-02-21 Plant Genetic Systems N.V. Plants with modified flowers
US5739082A (en) 1990-02-02 1998-04-14 Hoechst Schering Agrevo Gmbh Method of improving the yield of herbicide-resistant crop plants
US5908810A (en) 1990-02-02 1999-06-01 Hoechst Schering Agrevo Gmbh Method of improving the growth of crop plants which are resistant to glutamine synthetase inhibitors
US5434283A (en) 1990-04-04 1995-07-18 Pioneer Hi-Bred International, Inc. Edible endogenous vegetable oil extracted from rapeseeds of reduced stearic and palmitic saturated fatty acid content
US5198599A (en) 1990-06-05 1993-03-30 Idaho Resarch Foundation, Inc. Sulfonylurea herbicide resistance in plants
US5776760A (en) 1990-06-25 1998-07-07 Monsanto Company Glyphosate tolerant plants
US5463175A (en) 1990-06-25 1995-10-31 Monsanto Company Glyphosate tolerant plants
WO1992005251A1 (en) 1990-09-21 1992-04-02 Institut National De La Recherche Agronomique Dna sequence imparting cytoplasmic male sterility, mitochondrial genome, nuclear genome, mitochondria and plant containing said sequence and process for the preparation of hybrids
EP0571427A1 (en) 1991-02-13 1993-12-01 Hoechst Schering AgrEvo GmbH Plasmids containing dna-sequences that cause changes in the carbohydrate concentration and the carbohydrate composition in plants, as well as plant cells and plants containing these plasmids
US5731180A (en) 1991-07-31 1998-03-24 American Cyanamid Company Imidazolinone resistant AHAS mutants
US5767361A (en) 1991-07-31 1998-06-16 American Cyanamid Company Imidazolinone resistant AHAS mutants
EP0600983A1 (en) 1991-08-05 1994-06-15 Bio Tech Resources A fermentation process for producing natamycin.
US5402608A (en) 1992-02-27 1995-04-04 Chu; Rey-Chin Prefabricated built-up building construction
EP0559320A2 (en) 1992-02-29 1993-09-08 Tioxide Specialties Limited Water-in-oil emulsions
EP0663956A1 (en) 1992-08-12 1995-07-26 Hoechst Schering AgrEvo GmbH Dna sequences which lead to the formation of polyfructans (levans), plasmids containing these sequences as well as a process for preparing transgenic plants
WO1994004693A2 (en) 1992-08-26 1994-03-03 Zeneca Limited Novel plants and processes for obtaining them
WO1994009144A1 (en) 1992-10-14 1994-04-28 Zeneca Limited Novel plants and processes for obtaining them
WO1994011520A2 (en) 1992-11-09 1994-05-26 Zeneca Limited Novel plants and processes for obtaining them
EP0607730A1 (en) 1992-12-24 1994-07-27 International Business Machines Corporation Method of direct transferring of electrically conductive elements into a substrate
EP0609013A2 (en) 1993-01-21 1994-08-03 Matsushita Electric Industrial Co., Ltd. Recording and reproducing apparatus
EP0609022A2 (en) 1993-01-25 1994-08-03 Matsushita Electric Industrial Co., Ltd. Image encoding apparatus
WO1994021795A1 (en) 1993-03-25 1994-09-29 Ciba-Geigy Ag Novel pesticidal proteins and strains
US5969169A (en) 1993-04-27 1999-10-19 Cargill, Incorporated Non-hydrogenated canola oil for food applications
EP0709000A1 (en) 1993-07-15 1996-05-01 Siemens Ag Method and device for firing an m-pulse d.c./a.c. converter assembly consisting of a master d.c./a.c. converter and at least one slave d.c./a.c. converter
WO1995004826A1 (en) 1993-08-09 1995-02-16 Institut Für Genbiologische Forschung Berlin Gmbh Debranching enzymes and dna sequences coding them, suitable for changing the degree of branching of amylopectin starch in plants
EP0719338A1 (en) 1993-09-09 1996-07-03 Hoechst Schering AgrEvo GmbH Combination of dna sequences which enable the formation of modified starch in plant cells and plants, processes for the production of these plants and the modified starch obtainable therefrom
WO1995009910A1 (en) 1993-10-01 1995-04-13 Mitsubishi Corporation Gene that identifies sterile plant cytoplasm and process for preparing hybrid plant by using the same
US5965755A (en) 1993-10-12 1999-10-12 Agrigenetics, Inc. Oil produced from the Brassica napus
US6169190B1 (en) 1993-10-12 2001-01-02 Agrigenetics Inc Oil of Brassica napus
US5908975A (en) 1993-11-09 1999-06-01 E. I. Du Pont De Nemours And Company Accumulation of fructans in plants by targeted expression of bacterial levansucrase
EP0728213A1 (en) 1993-11-09 1996-08-28 E.I. Du Pont De Nemours And Company Transgenic fructan accumulating crops and methods for their production
US6270828B1 (en) 1993-11-12 2001-08-07 Cargrill Incorporated Canola variety producing a seed with reduced glucosinolates and linolenic acid yielding an oil with low sulfur, improved sensory characteristics and increased oxidative stability
WO1995026407A1 (en) 1994-03-25 1995-10-05 National Starch And Chemical Investment Holding Corporation Method for producing altered starch from potato plants
WO1995031553A1 (en) 1994-05-18 1995-11-23 Institut Für Genbiologische Forschung Berlin Gmbh DNA SEQUENCES CODING FOR ENZYMES CAPABLE OF FACILITATING THE SYNTHESIS OF LINEAR α-1,4 GLUCANS IN PLANTS, FUNGI AND MICROORGANISMS
US5824790A (en) 1994-06-21 1998-10-20 Zeneca Limited Modification of starch synthesis in plants
WO1995035026A1 (en) 1994-06-21 1995-12-28 Zeneca Limited Novel plants and processes for obtaining them
WO1996001904A1 (en) 1994-07-08 1996-01-25 Stichting Scheikundig Onderzoek In Nederland Production of oligosaccharides in transgenic plants
WO1996015248A1 (en) 1994-11-10 1996-05-23 Hoechst Schering Agrevo Gmbh Dna molecules that code for enzymes involved in starch synthesis, vectors, bacteria, transgenic plant cells and plants containing said molecules
WO1996019581A1 (en) 1994-12-22 1996-06-27 Hoechst Schering Agrevo Gmbh Dna molecules coding for debranching enzymes derived from plants
WO1996021023A1 (en) 1995-01-06 1996-07-11 Centrum Voor Plantenveredelings- En Reproduktieonderzoek (Cpro - Dlo) Dna sequences encoding carbohydrate polymer synthesizing enzymes and method for producing transgenic plants
WO1996027674A1 (en) 1995-03-08 1996-09-12 Hoechst Schering Agrevo Gmbh Modified starch from plants, plants synthesizing this starch, and process for its preparation
WO1996033270A1 (en) 1995-04-20 1996-10-24 American Cyanamid Company Structure-based designed herbicide resistant products
US5928937A (en) 1995-04-20 1999-07-27 American Cyanamid Company Structure-based designed herbicide resistant products
WO1996034968A2 (en) 1995-05-05 1996-11-07 National Starch And Chemical Investment Holding Corporation Improvements in or relating to plant starch composition
WO1996038567A2 (en) 1995-06-02 1996-12-05 Rhone-Poulenc Agrochimie Dna sequence of a gene of hydroxy-phenyl pyruvate dioxygenase and production of plants containing a gene of hydroxy-phenyl pyruvate dioxygenase and which are tolerant to certain herbicides
US20020031826A1 (en) 1995-06-07 2002-03-14 Nichols Scott E. Glucan-containing compositions and paper
US6284479B1 (en) 1995-06-07 2001-09-04 Pioneer Hi-Bred International, Inc. Substitutes for modified starch and latexes in paper manufacture
US5712107A (en) 1995-06-07 1998-01-27 Pioneer Hi-Bred International, Inc. Substitutes for modified starch and latexes in paper manufacture
US6229072B1 (en) 1995-07-07 2001-05-08 Adventa Technology Ltd Cytoplasmic male sterility system production canola hybrids
EP0837944A2 (en) 1995-07-19 1998-04-29 Rhone-Poulenc Agrochimie Mutated 5-enol pyruvylshikimate-3-phosphate synthase, gene coding for said protein and transformed plants containing said gene
WO1997011188A1 (en) 1995-09-19 1997-03-27 Planttec Biotechnologie Gmbh Plants which synthesise a modified starch, process for the production thereof and modified starch
WO1997020936A1 (en) 1995-12-06 1997-06-12 Zeneca Limited Modification of starch synthesis in plants
WO1997026362A1 (en) 1996-01-16 1997-07-24 Planttec Biotechnologie Gmbh Nucleic acid molecules from plants coding enzymes which participate in the starch synthesis
WO1997032985A1 (en) 1996-03-07 1997-09-12 Planttec Biotechnologie Gmbh Forschung & Entwicklung Nucleic acid molecules coding for debranching enzymes from maize
WO1997041218A1 (en) 1996-04-29 1997-11-06 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Herbicide resistant rice
WO1997042328A1 (en) 1996-05-06 1997-11-13 Planttec Biotechnologie Gmbh Nucleic acid molecules which code the potato debranching enzyme
EP0807551A2 (en) 1996-05-16 1997-11-19 Britax (Geco) S.A. Exterior mirror for a vehicle
WO1997044472A1 (en) 1996-05-17 1997-11-27 Planttec Biotechnologie Gmbh Nucleic acid molecules coding soluble maize starch synthases
WO1997045545A1 (en) 1996-05-29 1997-12-04 Hoechst Schering Agrevo Gmbh Nucleic acid molecules encoding enzymes from wheat which are involved in starch synthesis
WO1997047807A1 (en) 1996-06-12 1997-12-18 Pioneer Hi-Bred International, Inc. Substitutes for modified starch in paper manufacture
WO1997047808A1 (en) 1996-06-12 1997-12-18 Pioneer Hi-Bred International, Inc. Substitutes for modified starch in paper manufacture
WO1997047806A1 (en) 1996-06-12 1997-12-18 Pioneer Hi-Bred International, Inc. Substitutes for modified starch in paper manufacture
WO1998000549A1 (en) 1996-06-27 1998-01-08 The Australian National University MANIPULATION OF CELLULOSE AND/OR β-1,4-GLUCAN
US6063947A (en) 1996-07-03 2000-05-16 Cargill, Incorporated Canola oil having increased oleic acid and decreased linolenic acid content
US5773702A (en) 1996-07-17 1998-06-30 Board Of Trustees Operating Michigan State University Imidazolinone herbicide resistant sugar beet plants
WO1998003486A1 (en) 1996-07-24 1998-01-29 Bayer Aktiengesellschaft 1,3-dimethyl-5-fluoro-pyrazole-4-carboxamide derivatives, their preparation and their use as microbicides
WO1998020145A2 (en) 1996-11-05 1998-05-14 National Starch And Chemical Investment Holding Corporation Improvements in or relating to starch content of plants
WO1998022604A1 (en) 1996-11-20 1998-05-28 Pioneer Hi-Bred International, Inc. Methods of producing high-oil seed by modification of starch levels
WO1998027212A1 (en) 1996-12-19 1998-06-25 Planttec Biotechnologie Gmbh Novel nucleic acid molecules from maize and their use for the production of modified starch
WO1998027806A1 (en) 1996-12-24 1998-07-02 Pioneer Hi-Bred International, Inc. Oilseed brassica containing an improved fertility restorer gene for ogura cytoplasmic male sterility
WO1998032326A2 (en) 1997-01-24 1998-07-30 Pioneer Hi-Bred International, Inc. Methods for $i(agrobacterium)-mediated transformation
WO1998039460A1 (en) 1997-03-04 1998-09-11 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Nucleic acid molecules from artichoke ($i(cynara scolymus)) encoding enzymes having fructosyl polymerase activity
WO1998040503A1 (en) 1997-03-10 1998-09-17 Planttec Biotechnologie Gmbh Nucleic acid molecules encoding starch phosphorylase from maize
WO1999012950A2 (en) 1997-09-06 1999-03-18 National Starch And Chemical Investment Holding Corporation Improvements in or relating to stability of plant starches
WO1999024593A1 (en) 1997-11-06 1999-05-20 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Nucleic acid molecules which encode proteins having fructosyl transferase activity and methods for producing long-chain inulin
WO1999024586A1 (en) 1997-11-07 1999-05-20 Aventis Cropscience S.A. Chimeric hydroxy-phenyl pyruvate dioxygenase, dna sequence and method for obtaining plants containing such a gene, with herbicide tolerance
WO1999024585A1 (en) 1997-11-07 1999-05-20 Aventis Cropscience S.A. Mutated hydroxy-phenyl pyruvate dioxygenase, dna sequence and method for obtaining herbicide-tolerant plants containing such gene
WO1999034008A1 (en) 1997-12-24 1999-07-08 Aventis Cropscience S.A. Method for enzymatic preparation of homogentisate
WO1999053072A1 (en) 1998-04-09 1999-10-21 E.I. Du Pont De Nemours And Company Starch r1 phosphorylation protein homologs
WO1999058690A2 (en) 1998-05-08 1999-11-18 Aventis Cropscience Gmbh Nucleic acid molecules which code for enzymes derived from wheat and which are involved in the synthesis of starch
WO1999058688A2 (en) 1998-05-08 1999-11-18 Aventis Cropscience Gmbh Nucleic acid molecules which code for enzymes derived from wheat and which are involved in the synthesis of starch
WO1999058654A2 (en) 1998-05-13 1999-11-18 Planttec Biotechnologie Gmbh Forschung & Entwicklung Transgenic plants with a modified activity of a plastidial adp/atp translocator
WO1999057965A1 (en) 1998-05-14 1999-11-18 Aventis Cropscience Gmbh Sulfonylurea-tolerant sugar beet mutants
WO1999066050A1 (en) 1998-06-15 1999-12-23 National Starch And Chemical Investment Holding Corporation Improvements in or relating to plants and plant products
WO2000004173A1 (en) 1998-07-17 2000-01-27 Aventis Cropscience N.V. Methods and means to modulate programmed cell death in eukaryotic cells
WO2000008185A1 (en) 1998-07-31 2000-02-17 Aventis Cropscience Gmbh Nucleic acid molecule coding for beta-amylase, plants synthesizing a modified starch, method of production and applications
WO2000008175A2 (en) 1998-07-31 2000-02-17 Aventis Cropscience Gmbh Nucleic acid module coding for alpha glucosidase, plants that synthesize modified starch, methods for the production and use of said plants, and modified starch
WO2000008184A1 (en) 1998-07-31 2000-02-17 Aventis Cropscience Gmbh Plants which synthesize a modified starch, methods for producing the plants, their use, and the modified starch
WO2000011192A2 (en) 1998-08-25 2000-03-02 Pioneer Hi-Bred International, Inc. Plant glutamine: fructose-6-phosphate amidotransferase nucleic acids
WO2000014249A1 (en) 1998-09-02 2000-03-16 Planttec Biotechnologie Gmbh Nucleic acid molecules encoding an amylosucrase
WO2000022140A1 (en) 1998-10-09 2000-04-20 Planttec Biotechnologie Gmbh Forschung & Entwicklung NUCLEIC ACID MOLECULES WHICH CODE A BRANCHING ENZYME FROM BACTERIA OF THE GENUS NEISSERIA, AND A METHOD FOR PRODUCING α-1,6-BRANCHED α-1,4-GLUCANS
WO2000028052A2 (en) 1998-11-09 2000-05-18 Planttec Biotechnologie Gmbh Nucleic acid molecules from rice encoding an r1 protein and their use for the production of modified starch
WO2000047727A2 (en) 1999-02-08 2000-08-17 Planttec Biotechnologie Gmbh Forschung & Entwicklung Nucleic acid molecules encoding alternansucrase
US6323392B1 (en) 1999-03-01 2001-11-27 Pioneer Hi-Bred International, Inc. Formation of brassica napus F1 hybrid seeds which exhibit a highly elevated oleic acid content and a reduced linolenic acid content in the endogenously formed oil of the seeds
WO2000066747A1 (en) 1999-04-29 2000-11-09 Syngenta Limited Herbicide resistant plants
WO2000066746A1 (en) 1999-04-29 2000-11-09 Syngenta Limited Herbicide resistant plants
WO2000073422A1 (en) 1999-05-27 2000-12-07 Planttec Biotechnologie Gmbh Genetically modified plant cells and plants with an increased activity of an amylosucrase protein and a branching enzyme
WO2000077229A2 (en) 1999-06-11 2000-12-21 Aventis Cropscience Gmbh R1 protein from wheat and the use thereof for the production of modified strach
WO2001012826A2 (en) 1999-08-11 2001-02-22 Aventis Cropscience Gmbh Nucleic acid molecules derived from plants which code for enzymes which are involved in the synthesis of starch
WO2001012782A2 (en) 1999-08-12 2001-02-22 Aventis Cropscience Gmbh Transgenically modified plant cells and plants having modified gbssi- and be-protein activity
WO2001014569A2 (en) 1999-08-20 2001-03-01 Basf Plant Science Gmbh Increasing the polysaccharide content in plants
US6734341B2 (en) 1999-09-02 2004-05-11 Pioneer Hi-Bred International, Inc. Starch synthase polynucleotides and their use in the production of new starches
WO2001017333A1 (en) 1999-09-10 2001-03-15 Texas Tech University Transgenic fiber producing plants with increased expression of sucrose phosphate synthase
WO2001019975A2 (en) 1999-09-15 2001-03-22 National Starch And Chemical Investment Holding Corporation Plants having reduced activity in two or more starch-modifying enzymes
WO2001024615A1 (en) 1999-10-07 2001-04-12 Valigen (Us), Inc. Non-transgenic herbicide resistant plants
WO2001066704A2 (en) 2000-03-09 2001-09-13 Monsanto Technology Llc Methods for making plants tolerant to glyphosate and compositions thereof
WO2001065922A2 (en) 2000-03-09 2001-09-13 E. I. Du Pont De Nemours And Company Sulfonylurea-tolerant sunflower plants
US6768044B1 (en) 2000-05-10 2004-07-27 Bayer Cropscience Sa Chimeric hydroxyl-phenyl pyruvate dioxygenase, DNA sequence and method for obtaining plants containing such a gene, with herbicide tolerance
WO2001098509A2 (en) 2000-06-21 2001-12-27 Syngenta Participations Ag Grain processing method and transgenic plants useful therein
WO2002012172A1 (en) 2000-08-08 2002-02-14 Dow Agrosciences Llc Unsaturated oxime ethers and their use as fungicides
WO2002026995A1 (en) 2000-09-29 2002-04-04 Syngenta Limited Herbicide resistant plants
WO2002034923A2 (en) 2000-10-23 2002-05-02 Bayer Cropscience Gmbh Monocotyledon plant cells and plants which synthesise modified starch
WO2002036787A2 (en) 2000-10-30 2002-05-10 Bayer Cropscience S.A. Herbicide-tolerant plants through bypassing metabolic pathway
WO2002036782A2 (en) 2000-10-30 2002-05-10 Maxygen, Inc. Novel glyphosate n-acetyltransferase (gat) genes
WO2002046387A2 (en) 2000-12-07 2002-06-13 Syngenta Limited Plant derived hydroxy phenyl pyruvate dioxygenases (hppd) resistant against triketone herbicides and transgenic plants containing these dioxygenases
WO2002045485A1 (en) 2000-12-08 2002-06-13 Commonwealth Scienctific And Industrial Research Organisation Modification of sucrose synthase gene expression in plant tissue and uses therefor
WO2002079410A2 (en) 2001-03-30 2002-10-10 Basf Plant Science Gmbh Glucan chain length domains
WO2002101059A2 (en) 2001-06-12 2002-12-19 Bayer Cropscience Gmbh Transgenic plants synthesising high amylose starch
WO2003013226A2 (en) 2001-08-09 2003-02-20 Cibus Genetics Non-transgenic herbicide resistant plants
WO2003033540A2 (en) 2001-10-17 2003-04-24 Basf Plant Science Gmbh Starch
WO2003035617A2 (en) 2001-10-23 2003-05-01 Dow Agrosciences Llc Patent Department Derivatives of uk-2a
WO2003071860A2 (en) 2002-02-26 2003-09-04 Bayer Cropscience Gmbh Method for generating maize plants with an increased leaf starch content, and their use for making maize silage
WO2003092360A2 (en) 2002-04-30 2003-11-13 Verdia, Inc. Novel glyphosate-n-acetyltransferase (gat) genes
WO2004014138A1 (en) 2002-08-07 2004-02-19 Kumiai Chemical Industry Co., Ltd. Herbicide compositions
WO2004024928A2 (en) 2002-09-11 2004-03-25 Bayer Cropscience S.A. Transformed plants with enhanced prenylquinone biosynthesis
WO2004040012A2 (en) 2002-10-29 2004-05-13 Basf Plant Science Gmbh Compositions and methods for identifying plants having increased tolerance to imidazolinone herbicides
EP1559320A1 (en) 2002-10-31 2005-08-03 Ishihara Sangyo Kaisha, Ltd. 3-benzoyl-2,4,5-substituted pyridine derivatives or salts thereof and bactericides containing the same
WO2004053219A2 (en) 2002-12-05 2004-06-24 Jentex Corporation Abrasive webs and methods of making the same
WO2004056999A1 (en) 2002-12-19 2004-07-08 Bayer Cropscience Gmbh Plant cells and plants which synthesize a starch with an increased final viscosity
WO2004058723A1 (en) 2002-12-24 2004-07-15 Syngenta Participations Ag Biphenyl derivatives and their use as fungicides
WO2004078983A2 (en) 2003-03-07 2004-09-16 Basf Plant Science Gmbh Enhanced amylose production in plants
WO2004090140A2 (en) 2003-04-09 2004-10-21 Bayer Bioscience N.V. Methods and means for increasing the tolerance of plants to stress conditions
WO2005012515A2 (en) 2003-04-29 2005-02-10 Pioneer Hi-Bred International, Inc. Novel glyphosate-n-acetyltransferase (gat) genes
WO2005002359A2 (en) 2003-05-22 2005-01-13 Syngenta Participations Ag Modified starch, uses, methods for production thereof
WO2004106529A2 (en) 2003-05-28 2004-12-09 Basf Aktiengesellschaft Wheat plants having increased tolerance to imidazolinone herbicides
WO2005002324A2 (en) 2003-07-04 2005-01-13 Institut National De La Recherche Agronomique Method of producing double low restorer lines of brassica napus having a good agronomic value
WO2005012529A1 (en) 2003-07-31 2005-02-10 Toyo Boseki Kabushiki Kaisha Plant producing hyaluronic acid
WO2005017157A1 (en) 2003-08-15 2005-02-24 Commonwealth Scientific And Industrial Research Organisation (Csiro) Methods and means for altering fiber characteristics in fiber-producing plants
WO2005020673A1 (en) 2003-08-29 2005-03-10 Instituto Nacional De Technologia Agropecuaria Rice plants having increased tolerance to imidazolinone herbicides
WO2005030942A1 (en) 2003-09-30 2005-04-07 Bayer Cropscience Gmbh Plants with reduced activity of a class 3 branching enzyme
WO2005030941A1 (en) 2003-09-30 2005-04-07 Bayer Cropscience Gmbh Plants with increased activity of a class 3 branching enzyme
WO2005042474A1 (en) 2003-10-31 2005-05-12 Mitsui Chemicals, Inc. Diamine derivative, process for producing the same, and plant disease control agent containing the same as active ingredient
WO2005070917A1 (en) 2004-01-23 2005-08-04 Sankyo Agro Company, Limited 3-(dihydro(tetrahydro)isoquinolin-1-yl)quinolines
WO2005095617A2 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Plants with increased activity of a starch phosphorylating enzyme
WO2005095618A2 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Plants with reduced activity of the starch phosphorylating enzyme phosphoglucan, water dikinase
WO2005095632A2 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Methods for identifying proteins with starch phosphorylating enzymatic activity
WO2005095619A1 (en) 2004-03-05 2005-10-13 Bayer Cropscience Gmbh Plants with increased activity of multiple starch phosphorylating enzymes
WO2005093093A2 (en) 2004-03-22 2005-10-06 Basf Aktiengesellschaft Methods and compositions for analyzing ahasl genes
WO2006007373A2 (en) 2004-06-16 2006-01-19 Basf Plant Science Gmbh Polynucleotides encoding mature ahasl proteins for creating imidazolinone-tolerant plants
WO2005123927A1 (en) 2004-06-21 2005-12-29 Bayer Cropscience Gmbh Plants that produce amylopectin starch with novel properties
WO2006024351A1 (en) 2004-07-30 2006-03-09 Basf Agrochemical Products B.V. Herbicide-resistant sunflower plants, plynucleotides encoding herbicide-resistant acetohydroxy acid synthase large subunit proteins, and methods of use
WO2006015376A2 (en) 2004-08-04 2006-02-09 Basf Plant Science Gmbh Monocot ahass sequences and methods of use
WO2006018319A1 (en) 2004-08-18 2006-02-23 Bayer Cropscience Gmbh Plants with increased plastidic activity of r3 starch-phosphorylating enzyme
WO2006021972A1 (en) 2004-08-26 2006-03-02 Dhara Vegetable Oil And Foods Company Limited A novel cytoplasmic male sterility system for brassica species and its use for hybrid seed production in indian oilseed mustard brassica juncea
WO2006032538A1 (en) 2004-09-23 2006-03-30 Bayer Cropscience Gmbh Methods and means for producing hyaluronan
WO2006045633A1 (en) 2004-10-29 2006-05-04 Bayer Bioscience N.V. Stress tolerant cotton plants
WO2006060634A2 (en) 2004-12-01 2006-06-08 Basf Agrochemical Products, B.V. Novel mutation involved in increased tolerance to imidazolinone herbicides in plants
WO2006061215A2 (en) 2004-12-11 2006-06-15 Bayer Cropscience Ag 2-alkyl-cycloalk(en)yl-carboxamides
WO2006063862A1 (en) 2004-12-17 2006-06-22 Bayer Cropscience Ag Transformed plant expressing a dextransucrase and synthesizing a modified starch
WO2006072603A2 (en) 2005-01-10 2006-07-13 Bayer Cropscience Ag Transformed plant expressing a mutansucrase and synthesizing a modified starch
JP2006304779A (en) 2005-03-30 2006-11-09 Toyobo Co Ltd Plant producing hexosamine in high productivity
WO2006103107A1 (en) 2005-04-01 2006-10-05 Bayer Cropscience Ag Phosphorylated waxy potato starch
WO2006108702A1 (en) 2005-04-08 2006-10-19 Bayer Cropscience Ag High-phosphate starch
WO2006129204A2 (en) 2005-05-31 2006-12-07 Devgen Nv Rnai for control of insects and arachnids
WO2006133827A2 (en) 2005-06-15 2006-12-21 Bayer Bioscience N.V. Methods for increasing the resistance of plants to hypoxic conditions
WO2006136351A2 (en) 2005-06-24 2006-12-28 Bayer Bioscience N.V. Methods for altering the reactivity of plant cell walls
WO2007003961A2 (en) 2005-06-30 2007-01-11 Prosidion Limited Gpcr agonists
WO2007009823A1 (en) 2005-07-22 2007-01-25 Bayer Cropscience Ag Overexpression of starch synthase in plants
WO2007014290A2 (en) 2005-07-26 2007-02-01 E. I. Du Pont De Nemours And Company Fungicidal carboxamides
WO2007024782A2 (en) 2005-08-24 2007-03-01 Pioneer Hi-Bred International, Inc. Compositions providing tolerance to multiple herbicides and methods of use thereof
WO2007027777A2 (en) 2005-08-31 2007-03-08 Monsanto Technology Llc Nucleotide sequences encoding insecticidal proteins
WO2007035650A2 (en) 2005-09-16 2007-03-29 Monsanto Technology Llc Methods for genetic control of insect infestations in plants and compositions thereof
WO2007074405A2 (en) 2005-09-16 2007-07-05 Devgen Nv Dsrna as insect control agent
WO2007039315A1 (en) 2005-10-05 2007-04-12 Bayer Cropscience Ag Plants with an increased production of hyaluronan ii
WO2007039314A2 (en) 2005-10-05 2007-04-12 Bayer Cropscience Ag Plants with increased hyaluronan production
WO2007039316A1 (en) 2005-10-05 2007-04-12 Bayer Cropscience Ag Improved methods and means for producings hyaluronan
WO2007080126A2 (en) 2006-01-12 2007-07-19 Devgen N.V. Dsrna as insect control agent
WO2007080127A2 (en) 2006-01-12 2007-07-19 Devgen N.V. Dsrna as insect control agent
WO2007103567A2 (en) 2006-03-09 2007-09-13 E. I. Dupont De Nemours & Company Polynucleotide encoding a maize herbicide resistance gene and methods for use
WO2007107302A2 (en) 2006-03-21 2007-09-27 Bayer Bioscience N.V. Novel genes encoding insecticidal proteins
WO2007107326A1 (en) 2006-03-21 2007-09-27 Bayer Bioscience N.V. Stress resistant plants
EP1999263A1 (en) 2006-03-21 2008-12-10 Bayer BioScience N.V. Stress resistant plants
EP1999141A2 (en) 2006-03-21 2008-12-10 Bayer BioScience N.V. Novel genes encoding insecticidal proteins
WO2008003746A1 (en) 2006-07-06 2008-01-10 Bayer Cropscience Sa N-(4-pyridin-2-ylbutyl) carboxamide derivatives, their process of preparation and their use as fungicides
WO2008013622A2 (en) 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2008081017A1 (en) 2007-01-03 2008-07-10 Bayer Cropscience Ag New n-alkynylcarboxamide derivatives
WO2008101976A1 (en) 2007-02-22 2008-08-28 Bayer Cropscience Sa Fungicide n-(3-phenylpropyl)carboxamide derivatives
WO2008150473A2 (en) 2007-05-30 2008-12-11 Syngenta Participations Ag Cytochrome p450 genes conferring herbicide resistance
WO2008148570A1 (en) 2007-06-08 2008-12-11 Syngenta Participations Ag Pyrazole carboxylic acid amides useful as microbiocides
WO2009012998A1 (en) 2007-07-26 2009-01-29 Syngenta Participations Ag Novel microbiocides
WO2009068313A2 (en) 2007-11-28 2009-06-04 Bayer Bioscience N.V. Brassica plant comprising a mutant indehiscent allele
WO2009094442A2 (en) 2008-01-22 2009-07-30 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
WO2009144079A1 (en) 2008-04-14 2009-12-03 Bayer Bioscience N.V. New mutated hydroxyphenylpyruvate dioxygenase, dna sequence and isolation of plants which are tolerant to hppd inhibitor herbicides
WO2009127718A2 (en) 2008-04-18 2009-10-22 Syngenta Participations Ag Novel microbiocides
WO2009127726A1 (en) 2008-04-18 2009-10-22 Syngenta Participations Ag Novel microbiocides
WO2009127722A1 (en) 2008-04-18 2009-10-22 Syngenta Participations Ag Novel microbiocides
WO2010006732A2 (en) 2008-07-17 2010-01-21 Bayer Bioscience N.V. Brassica plant comprising a mutant indehiscent allelle
WO2010012795A1 (en) 2008-08-01 2010-02-04 Bayer Cropscience Sa Fungicidal n-(2-phenoxyethyl)carboxamide derivatives and their aza, thia and sila analogues
WO2010015681A1 (en) 2008-08-07 2010-02-11 Bayer Cropscience Sa Fungicidal n-(2-pyridylpropyl)carboxamide derivatives and their oxa, aza and thia analogues
WO2010025451A2 (en) 2008-08-29 2010-03-04 Dow Agrosciences Llc 5,8-difluoro-4-(2-(4-(heteroaryloxy)-phenyl)ethylamino)quinazolines and their use as agrochemicals
WO2010063700A2 (en) 2008-12-05 2010-06-10 Syngenta Participations Ag Novel microbiocides
WO2010094666A2 (en) 2009-02-17 2010-08-26 Bayer Cropscience Ag Fungicidal n-(phenylcycloalkyl)carboxamide, n-(benzylcycloalkyl)carboxamide and thiocarboxamide derivatives
WO2010106071A1 (en) 2009-03-18 2010-09-23 Syngenta Participations Ag N-hydroxy-l-methyl-lh-pyrazole-4-carboxamide derivatives and their use as microbiocides
WO2011045355A1 (en) 2009-10-16 2011-04-21 Syngenta Participations Ag Novel microbiocides

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
BARRY ET AL., CURR. TOPICS PLANT PHYSIOL., vol. 7, 1992, pages 139 - 145
BIOORGANICS AND MEDICINAL CHEMISTRY LETTERS, 2006, pages 2014
COMAI ET AL., SCIENCE, vol. 221, 1983, pages 370 - 371
CRICKMORE ET AL., MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, vol. 62, 1998, pages 807 - 813
GASSER ET AL., J. BIOL. CHEM., vol. 263, 1988, pages 4280 - 4289
JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 7, 2005, pages 109
JOURNAL OF MEDICINAL CHEMISTRY, 2002, pages 3887
JOURNAL OF THE CHEMICAL SOCIETY, vol. 1, 2001, pages 358
MOELLENBECK ET AL., NAT. BIOTECHNOL., vol. 19, 2001, pages 668 - 72
SCHNEPF ET AL., APPLIED ENVIRONM. MICROBIOL., vol. 71, 2006, pages 1765 - 1774
SHAH ET AL., SCIENCE, vol. 233, 1986, pages 478 - 481
TETRAHEDRON, 2005, pages 11689
TETRAHEDRON, vol. 23, 1976, pages 2421
TETRAHEDRON, vol. 53, 1997, pages 4935
TRANEL, WRIGHT, WEED SCIENCE, vol. 50, 2002, pages 700 - 712

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9499563B2 (en) 2009-05-15 2016-11-22 Katholieke Universiteit Leuven Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors
US9232799B2 (en) 2010-06-03 2016-01-12 Bayer Intellectual Property Gmbh N-[(het)arylethyl)] pyrazole(thio)carboxamides and their heterosubstituted analogues
US9556205B2 (en) 2010-06-03 2017-01-31 Bayer Intellectual Property Gmbh Fungicide N-[(trisubstitutedsilyl)methyl]-carboxamide derivatives
US9320276B2 (en) 2010-11-02 2016-04-26 Bayer Intellectual Property Gmbh N-hetarylmethyl pyrazolylcarboxamides
US9132129B2 (en) 2010-11-15 2015-09-15 Katholieke Universiteit Leuven Antiviral compounds
US9725414B2 (en) 2011-11-30 2017-08-08 Bayer Intellectual Property Gmbh Fungicidal N-bicycloalkyl and N-tricycloalkyl pyrazole-4-(thio)carboxamide derivatives
WO2013079566A3 (en) * 2011-11-30 2013-07-25 Bayer Intellectual Property Gmbh Fungicidal n- bicycloalkyl and n-tricycloalkyl pyrazole - 4 - (thio) carboxamide derivatives
WO2013167651A1 (en) * 2012-05-11 2013-11-14 Syngenta Participations Ag Crop enhancement
KR20170010446A (en) 2012-07-12 2017-01-31 닛산 가가쿠 고교 가부시키 가이샤 Oxime-substituted amide compound and pest control agent
US9920046B2 (en) 2012-07-12 2018-03-20 Nissan Chemical Industries, Ltd. Oxime-substituted amide compound and pest control agent
KR20150036434A (en) 2012-07-12 2015-04-07 닛산 가가쿠 고교 가부시키 가이샤 Oxime-substituted amide compound and pest control agent
US9434684B2 (en) 2012-07-12 2016-09-06 Nissan Chemical Industries, Ltd. Oxime-substituted amide compound and pest control agent
WO2014010737A1 (en) 2012-07-12 2014-01-16 日産化学工業株式会社 Oxime-substituted amide compound and pest control agent
US9617220B2 (en) 2012-08-07 2017-04-11 Bayer Cropscience Ag Method for the preparation of perfluoroalkyl containing pyrazoles carboxylates
US9556121B2 (en) 2012-11-13 2017-01-31 Bayer Cropscience Ag Pyridyloxyalkyl carboxamides and use thereof as endoparasiticides and nematicides
EP2730570A1 (en) * 2012-11-13 2014-05-14 Bayer CropScience AG Pyridyloxyal alkyl carboxamides and their use as endoparasiticides and nematicide
WO2014076015A1 (en) * 2012-11-13 2014-05-22 Bayer Cropscience Ag Pyridyloxyalkyl carboxamides and use thereof as endoparasiticides and nematicides
US9765049B2 (en) 2013-06-26 2017-09-19 Bayer Cropscience Ag N-cycloalkyl-N-[(fusedphenyl)methylene]-(thio)carboxamide derivatives
WO2014206954A1 (en) * 2013-06-26 2014-12-31 Bayer Cropscience Ag N-cycloalkyl-n-[(fusedphenyl)methylene]-(thio)carboxamide derivatives
US10029986B2 (en) 2014-02-18 2018-07-24 Nissan Chemical Industries, Ltd. Alkynyl pyridine-substituted amide compound and pesticide
WO2015144657A1 (en) * 2014-03-27 2015-10-01 Bayer Cropscience Ag Use of pyridyloxyalkylcarboxamides for the control of unwanted microorganisms
EP3189043B1 (en) * 2014-09-03 2020-11-18 C4x Discovery Limited Therapeutic compounds as inhibitors of the orexin-1 receptor

Also Published As

Publication number Publication date
EP2576517B1 (en) 2014-12-17
BR112012030607B1 (en) 2018-06-26
JP5730993B2 (en) 2015-06-10
CN102918028B (en) 2016-04-27
PL2576517T3 (en) 2015-06-30
BR112012030607A2 (en) 2015-09-29
US20130079302A1 (en) 2013-03-28
EP2576517A1 (en) 2013-04-10
MX2012013896A (en) 2012-12-17
CL2012003358A1 (en) 2013-01-25
JP2013532138A (en) 2013-08-15
CO6660480A2 (en) 2013-04-30
AR081834A1 (en) 2012-10-24
AU2011260333A1 (en) 2012-11-08
CA2796194A1 (en) 2011-12-08
ES2532971T3 (en) 2015-04-06
US8999956B2 (en) 2015-04-07
AU2011260333B2 (en) 2014-07-24
KR20130088022A (en) 2013-08-07
CN102918028A (en) 2013-02-06

Similar Documents

Publication Publication Date Title
US9375004B2 (en) 5-halogenopyrazolecarboxamides
EP2576517B1 (en) N-[(het)arylalkyl)]pyrazole (thio)carboxamides and their heterosubstituted analogues
US9232799B2 (en) N-[(het)arylethyl)] pyrazole(thio)carboxamides and their heterosubstituted analogues
EP2630138B1 (en) 1-(heterocyclic carbonyl)-2-substituted pyrrolidines and their use as fungicides
EP2630135B1 (en) 1-(heterocyclic carbonyl) piperidines
EP2640191A1 (en) 5-halogenopyrazole(thio)carboxamides
EP2576571B1 (en) Fungicide n-[(trisubstitutedsilyl)methyl]-carboxamide derivatives
US10093611B2 (en) Benzocycloalkenes as antifungal agents

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201180027220.8

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11723939

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2796194

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2011723939

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2011260333

Country of ref document: AU

Date of ref document: 20110601

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20127031072

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 13700716

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2013512887

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: MX/A/2012/013896

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 10432/DELNP/2012

Country of ref document: IN

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 12232532

Country of ref document: CO

WWE Wipo information: entry into national phase

Ref document number: A201214917

Country of ref document: UA

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112012030607

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112012030607

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20121130