WO2015010832A1 - Microbiocidal heterocyclic derivatives - Google Patents

Microbiocidal heterocyclic derivatives Download PDF

Info

Publication number
WO2015010832A1
WO2015010832A1 PCT/EP2014/062894 EP2014062894W WO2015010832A1 WO 2015010832 A1 WO2015010832 A1 WO 2015010832A1 EP 2014062894 W EP2014062894 W EP 2014062894W WO 2015010832 A1 WO2015010832 A1 WO 2015010832A1
Authority
WO
WIPO (PCT)
Prior art keywords
crc
alkyl
nhch
cycloalkyl
alkynyl
Prior art date
Application number
PCT/EP2014/062894
Other languages
French (fr)
Inventor
Farhan BOU HAMDAN
Alan Joseph Hennessy
Marco STENTA
Fredrik Cederbaum
Stephane André Marie JEANMART
Werner Zambach
Original Assignee
Syngenta Participations 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 Syngenta Participations Ag filed Critical Syngenta Participations Ag
Publication of WO2015010832A1 publication Critical patent/WO2015010832A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the present invention relates to microbiocidal heterobicyclic derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity.
  • the invention also relates to preparation of these heterobicyclic derivatives, to heterobicyclic derivatives used as intermediates in the preparation of these heterobicyclic derivatives, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the heterobicyclic derivatives, to preparation of these compositions and to use of the
  • heterobicyclic derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.
  • the present invention provides compounds of formula I:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen, CrC 6 alkyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl in which the alkyl, alkynyl and cycloalkyl groups are optionally substituted by one or more R 6 ;
  • R 2 is heterocyclyl, which can be optionally substituted by one or more R 6 ;
  • R 4 is C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which the alkynyl, cycloalkyl, aryl and heterocyclyl groups are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, CrC 6 alkyl, CrC 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyl, C 2 - C 6 alkynyloxy, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyloxy or aryl, in which the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and aryl groups are optionally substituted by one or more R 6 ;
  • R 6 is hydrogen, halogen, cyano, hydroxyl, amino, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, CrC 6 haloalkoxy, CrC 6 alkylthio, CrC 6 haloalkylthio, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 - C 6 alkenyloxy, C 2 -C 6 alkenylthio, C 2 -C 6 haloalkenyloxy, C 2 -C 6 haloalkenylthio, C 2 -C 6 alkynyl, C 2 - C 6 alkynyloxy, C 2 -C 6 alkynylthio, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 3 -C 6 cycloalkyloxy, C 3 - C 6 cycloalkylthio, C 3
  • Cealkyl Cealkyl
  • -C( NO(Ci-C 6 alkyl))Ci-C 6 alkyl
  • -C( NO(Ci-C 6 alkyl))C 2 -C 6 alkenyl
  • -C( NO(C
  • L 1 and L 2 are independently a direct bond, -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 - z, -NR 5 -z, -NR 5 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z, -NR 5 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 - C(R 6 ) 2 -NR 5 -z, -C(R 6 ) 2 -0-z, -C(R 6 ) 2
  • substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents, e.g. one to three substituents. Normally not more than three such optional substituents are present at the same time.
  • substituents are indicated as being substituted, e.g. alkyl, this includes those groups that are part of other groups, e.g. the alkyl in alkylthio.
  • halogen refers to fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
  • Alkyl substituents may be straight-chained or branched. Alkyl on its own or as part of another substituent is, depending upon the number of carbon atoms mentioned, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso- propyl, iso-butyl, sec-butyl, tert-butyl or iso-amyl.
  • Alkenyl substituents can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Examples are vinyl and allyl.
  • the alkenyl groups are preferably C 2 -C 6 , more preferably C 2 -C 4 and most preferably C 2 -C 3 alkenyl groups.
  • Alkynyl substituents can be in the form of straight or branched chains. Examples are ethynyl and propargyl.
  • the alkynyl groups are preferably C 2 -C 6 , more preferably C 2 -C 4 and most preferably C 2 -C 3 alkynyl groups.
  • Haloalkyl groups may contain one or more identical or different halogen atoms and, for example, may stand for CH 2 CI, CHCI 2 , CCI 3 , CH 2 F, CHF 2 , CF 3 , CF 3 CH 2 , CH 3 CF 2 , CF 3 CF 2 or CCI 3 CCI 2 .
  • Haloalkenyl groups are alkenyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 2,2-difluorovinyl or 1 ,2- dichloro-2-fluoro-vinyl.
  • Haloalkynyl groups are alkynyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 1 -chloro-prop-2-ynyl.
  • Alkoxy means a radical -OR, where R is alkyl, e.g. as defined above.
  • Alkoxy groups include, but are not limited to, methoxy, ethoxy, 1 -methylethoxy, propoxy, butoxy, 1 - methylpropoxy and 2-methylpropoxy.
  • Cyano means a -CN group.
  • Amino means an -NH 2 group. Hydroxyl or hydroxy stands for a -OH group.
  • Aryl means a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
  • Monocyclic and bicyclic aromatic ring systems are preferred.
  • monocyclic heteocyclyl may be a 4- to 7-membered ring containing one to three heteroatoms selected from oxygen, nitrogen and sulfur, more preferably selected from nitrogen and oxygen.
  • Bicyclic heterocyclyl may be a 7- to 1 1 -membered bicyclic ring containing one to five heteroatoms, preferably one to three heteroatoms, selected from oxygen, nitrogen and sulfur.
  • the different rings of bi- and tricyclic heterocyclyl may be linked via one atom belonging to two different rings (spiro), via two adjacent ring atoms belonging to two different rings (annelated) or via two different, not adjacent ring atoms belonging to two different rings (bridged).
  • saturated heterocyclyl examples include azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, thiazolidinyl, isoxazolidinyl, isothiazolidinyl, oxadiazolidinyl, thiadiazolidinyl, dioxolanyl, dithiolanyl, piperidinyl, piperazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, dithianyl and morpholinyl.
  • Examples for partially unsaturated heterocyclyl are pyrrolinyl, dihydrofuranyl, dihydrothienyl, pyrazolinyl, imidazolinyl, oxazolinyl, thiazolinyl, isoxazolinyl, isothiazinyl, oxadiazolinyl, thiadiazolinyl, dihydropyranyl, dihydrothiopyranyl, oxathiolyl and oxazinyl.
  • aromatic heterocyclyl examples include furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothiophenyl, benzofuranyl,
  • Heterocyclyl rings do not contain adjacent oxygen ring atoms, adjacent sulfur ring atoms or adjacent oxygen and sulfur ring atoms.
  • a link to a heterocyclyl group can be via a carbon atom or via a nitrogen atom.
  • asymmetric carbon atoms in a compound of formula I means that the compounds may occur in optically isomeric forms, i.e. enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond.
  • Formula I is intended to include all those possible isomeric forms and mixtures thereof.
  • the present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula I.
  • formula I is intended to include all possible tautomers.
  • the present invention includes all possible tautomeric forms for a compound of formula I.
  • the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
  • N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book "Heterocyclic N- oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 2 is preferably O or S.
  • X 3 is preferably O or NR 5 , more preferably O or NH.
  • X 4 is O or NR 5 ; more preferably O or NH.
  • R 1 is hydrogen, CrC 6 alkyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl in which the alkyl, alkynyl and cycloalkyl groups are optionally substituted by one or more R 6 .
  • R 1 is hydrogen, CrC 6 alkyl or C 3 -C 6 cycloalkyl, in which the alkyl and cycloalkyl groups are optionally substituted by one or more R 6 , more preferably hydrogen or CrC 6 alkyl, even more preferably methyl.
  • R 2 is heterocyclyl, which can be optionally substituted by one or more R 6 ;
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system, more preferably 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl.
  • R 4 is C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which the alkynyl, cycloalkyl, aryl and heterocyclyl groups are optionally substituted by one or more R 6 .
  • R 4 is C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which cycloalkyl, aryl and heterocyclyl are optionally substituted by one or more R 6 , more preferably aryl or 5- to 6- membered aromatic heterocyclic ring system, even more preferably phenyl or thienyl.
  • R 5 is hydrogen, CrC 6 alkyl, CrC 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 alkynyloxy, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyloxy or aryl, in which the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and aryl groups are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, CrC 6 alkyl, d-C 6 alkoxy; more preferably hydrogen or d- C 6 alkyl, even more preferably hydrogen or methyl.
  • R 6 is hydrogen, halogen, cyano, nitro, hydroxyl, amino, CrC 6 alkyl, CrC 6 haloalkyl, d- C 6 alkoxy, CrC 6 haloalkoxy, CrC 6 alkylthio, CrC 6 haloalkylthio, C 2 -C 6 alkenyl, C 2 - C 6 haloalkenyl, C 2 -C 6 alkenyloxy, C 2 -C 6 alkenylthio, C 2 -C 6 haloalkenyloxy, C 2 -C 6 haloalkenylthio, C 2 -C 6 alkynyl, C 2 -C 6 alkynyloxy, C 2 -C 6 alkynylthio, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 3 - C 6 cycloalkyloxy, C 3 -C 6 cycloalkylthi
  • Cealkyl Cealkyl
  • R 6 is halogen, cyano, nitro, hydroxyl, amino, CrC 6 alkyl, CrC 6 haloalkyl, d-
  • L 1 and L 2 are independently a direct bond, -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 - C(R 6 ) 2 -z, -NR 5 -z, -NR 5 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z, -NR 5 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -C(R 6 ) 2 -z, - C(R 6 ) 2 -C(R 6 ) 2 -NR 5 -z, -C(R 6 ) 2 -0-z, -C(R 6 ) 2 -0-C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2
  • L 1 is preferably -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z, more preferably -C(R 6 ) 2 -z or -C(R 6 ) 2 -C(R 6 ) 2 -z, even more preferably -C(CH 3 ) 2 -z.
  • L 2 is preferably -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or
  • the compound of formula I is a compound wherein:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen, CrC 6 alkyl or C 3 -C 6 cycloalkyl, in which the alkyl and cycloalkyl groups are optionally substituted by one or more R 6 ;
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which cycloalkyl, aryl and heterocyclyl are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, d-C 6 alkyl or CrC 6 alkoxy;
  • R 6 is halogen, cyano, nitro, hydroxyl, amino, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, Ci- Cehaloalkoxy, CrC 6 alkylthio, CrC 6 haloalkylthio, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 - C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 alkynyloxy, C 3 -C 6 cycloalkyl, C 3 - C 6 halocycloalkyl, C 3 -C 6 cycloalkyloxy or C 3 -C 6 halocycloalkyloxy;
  • L 1 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • L 2 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • the compound of formula I is a compound wherein:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen, CrC 6 alkyl or C 3 -C 6 cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R 6 ;
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, CrC 6 alkyl or CrC 6 alkoxy
  • R 6 is halogen, cyano, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, CrC 6 haloalkoxy, C 2 -C 6 alkenyl,
  • L 1 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • L 2 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • the compound of formula I is a compound wherein:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen or CrC 6 alkyl
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is aryl or 5- to 6-membered aromatic heterocyclic ring system
  • R 5 is hydrogen or CrC 6 alkyl
  • R 6 is halogen, cyano, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, CrC 6 haloalkoxy, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl;
  • L 1 is -C(R 6 ) 2 -z or -C(R 6 ) 2 -C(R 6 ) 2 -z
  • L 2 is -C(R 6 ) 2 -C(R 6 ) 2 -z or -C(R 6 ) 2 -0-z;
  • the compound of formula I is a compound wherein:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is methyl
  • R 2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
  • R 4 is phenyl or thienyl
  • R 5 is hydrogen or methyl
  • R 6 is fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl;
  • L 1 is -C(R 6 ) 2 -z or -C(R 6 ) 2 -C(R 6 ) 2 -z;
  • L 2 is -C(R 6 ) 2 -C(R 6 ) 2 -z or -C(R 6 ) 2 -0-z;
  • the compound of formula I is a compound wherein:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is methyl
  • R 2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
  • R 4 is phenyl or thienyl
  • R 5 is hydrogen or methyl
  • L 1 is -C(CH 3 ) 2 -z;
  • L 2 is CH 2 CH(0(CrC 6 alkyl))-z;
  • the compound of formula I is a compound wherein:
  • X 2 and X 3 are independently O, S or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen, CrC 6 alkyl or C 3 -C 6 cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R 6 ;
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, d-C 6 alkyl or CrC 6 alkoxy
  • R 6 is halogen, cyano, nitro, hydroxyl, amino, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, C C 6 haloalkoxy, CrC 6 alkylthio, CrC 6 haloalkylthio, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 - C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 alkynyloxy, C 3 -C 6 cycloalkyl, C 3 - C 6 halocycloalkyl, C 3 -C 6 cycloalkyloxy or C 3 -C 6 halocycloalkyloxy;
  • L 1 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • L 2 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z; or a salt or a N-oxide thereof.
  • the compound of formula I is a compound wherein:
  • X 2 is O or S
  • X 3 is O or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen, CrC 6 alkyl or C 3 -C 6 cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R 6 ;
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, CrC 6 alkyl or CrC 6 alkoxy
  • R 6 is halogen, cyano, nitro, hydroxyl, amino, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, C C 6 haloalkoxy, CrC 6 alkylthio, CrC 6 haloalkylthio, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 - C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 2 -C 6 alkynyl, C 2 -C 6 alkynyloxy, C 3 -C 6 cycloalkyl, C 3 - C 6 halocycloalkyl, C 3 -C 6 cycloalkyloxy or C 3 -C 6 halocycloalkyloxy;
  • L 1 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • L 2 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z; or a salt or a N-oxide thereof.
  • the compound of formula I is a compound wherein:
  • X 2 is O or S
  • X 3 is O or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen, CrC 6 alkyl or C 3 -C 6 cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R 6 ;
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is C 3 -C 6 cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R 6 ;
  • R 5 is hydrogen, d-C 6 alkyl or CrC 6 alkoxy
  • R 6 is halogen, cyano, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, CrC 6 haloalkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 -C 6 alkynyloxy, C 3 -C 6 cycloalkyl;
  • L 1 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • L 2 is -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -C(R 6 ) 2 -C(R 6 ) 2 -z, -C(R 6 ) 2 -NR 5 -z or -C(R 6 ) 2 -0-z;
  • the compound of formula I is a compound wherein:
  • X 2 is O or S
  • X 3 is O or NR 5 ;
  • X 4 is O or NR 5 ;
  • R 1 is hydrogen or CrC 6 alkyl
  • R 2 is a 5- to 6-membered aromatic heterocyclic ring system
  • R 4 is aryl or 5- to 6-membered aromatic heterocyclic ring system
  • R 5 is hydrogen or CrC 6 alkyl
  • R 6 is halogen, cyano, CrC 6 alkyl, CrC 6 haloalkyl, CrC 6 alkoxy, CrC 6 haloalkoxy, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl;
  • L 1 is -C(R 6 ) 2 -z or -C(R 6 ) 2 -C(R 6 ) 2 -z;
  • L 2 is -C(R 6 ) 2 -C(R 6 ) 2 -z or -C(R 6 ) 2 -0-z;
  • the compound of formula I is a compound wherein:
  • X 2 is O or S
  • X 3 is O or NH
  • X 4 is O or NH
  • R 1 is methyl
  • R 2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
  • R 4 is phenyl or thienyl
  • R 6 is fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl;
  • L 1 is -C(R 6 ) 2 -z or -C(R 6 ) 2 -C(R 6 ) 2 -z;
  • L 2 is -C(R 6 ) 2 -C(R 6 ) 2 -z or -C(R 6 ) 2 -0-z;
  • R 2 s 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
  • R 4 s phenyl or thienyl
  • the invention also relates to compounds of formula l-a:
  • X 1 , X 2 , X 3 , X 4 , R 2 , R 3 , R 4 , L 1 and L 2 have the definitions as described for formula I.
  • Preferred definitions of X 1 , X 2 , X 3 , X 4 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I.
  • X 1 , X 2 , X 3 , X 4 , R 1 , R 3 , R 4 , L 1 and L 2 have the definition as described for formula I.
  • Preferred definitions of X 1 , X 2 , X 3 , X 4 , R 1 , R 3 , R 4 , L 1 and L 2 are as defined for formula I.
  • the invention also relates to compounds of formula l-c:
  • X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 have the definitions as described for formula I.
  • Preferred definitions of X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I.
  • the invention also relates to compounds of formula l-d:
  • X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 have the definitions as described for formula I.
  • Preferred definitions of X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I.
  • the invention also relates to compounds of formula l-e:
  • X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 and L 2 have the definitions as described for formula I.
  • Preferred definitions of X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 and L 2 are as defined for formula I.
  • X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 4 , L 1 and L 2 have the definitions as described for formula I.
  • Preferred definitions of X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 4 , L 1 and L 2 are as defined for formula I.
  • X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 and L 1 have the definitions as described for formula I.
  • Preferred definitions of X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 and L 1 are as defined for formula I.
  • the invention also relates to compounds of formula l-h:
  • X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , L 1 and L 2 have the definitions as described for formula I.
  • Preferred definitions of X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , L 1 and L 2 are as defined for formula I.
  • Compounds of the present invention can be made as shown in the following schemes, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).
  • the compounds of formula 1-1 wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I can be obtained by transformation of a compound of formula II, wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 4 and L 2 are as defined for formula I with a compound of formula III, wherein R 3 and L 1 are as defined for formula I and a peptide coupling reagent, such as BOP, EDCI or HOAT, and a base.
  • a peptide coupling reagent such as BOP, EDCI or HOAT
  • the compounds of formula 1-1 wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 4 and L 2 are as defined for formula I with a compound of formula III, wherein R 3 and L 1 are as defined for formula I, and a base, such as pyridine or triethylamine. This is shown in Scheme 2.
  • the compounds of formula I-2 wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 4 and L 2 are as defined for formula I with a compound of formula V, wherein R 3 and L 1 are as defined for formula I, and a base, such as pyridine or triethylamine. This is shown in Scheme 3.
  • the compounds of formula IV wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 4 and L 2 are as defined for formula I can be obtained by transformation of a compound of formula II, wherein X 1 , X 2 , X 3 , R 1 , R 2 , R 4 and L 2 are as defined for formula I with a chlorination reagent, such as oxalyl chloride, thionyl chloride or phosphoryl chloride. This is shown in Scheme 4.
  • a chlorination reagent such as oxalyl chloride, thionyl chloride or phosphoryl chloride.
  • the compounds of formula I wherein X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 4 , L 1 and L 2 are as defined for formula I can be obtained by transformation of a compound of formula VI, wherein X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 and L 1 are as defined for formula I with a compound of formula VII, wherein R 4 and L 2 are as defined for formula I and R 7 is halogen, preferably chloro or bromo, or a sulfonate, preferably a mesylate or tosylate, and a base. This is shown in Scheme 5.
  • novel compounds of formula I have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.
  • the compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man.
  • the novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants.
  • the compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
  • fungicide as used herein means a compound that controls, modifies, or prevents the growth of fungi.
  • fungicidally effective amount means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
  • compositions comprising a compound of formula I before planting: seed, for example, can be dressed before being sown.
  • the active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation.
  • the composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
  • the compounds according to present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management.
  • the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
  • the compounds of formula I are for example, effective against Fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses.
  • These Fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses are for example:
  • Absidia corymbifera Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terrus, Aureobasidium spp.
  • Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. contributing B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. tropicalis, Cephaloascus fragrans, Ceratocystis spp, Cercospora spp. including C.
  • Coccidioides immitis Coccidioides immitis, Cochliobolus spp, Colletotrichum spp. including C. musae,
  • Cryptococcus neoformans Diaporthe spp, Didymella spp, Drechslera spp, Elsinoe spp, Epidermophyton spp, Erwinia amylovora, Erysiphe spp. including E. cichoracearum,
  • Eutypa lata Fusarium spp. including F. culmorum, F. graminearum, F. langsethiae, F.
  • Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P. philippinensis and P. sorghi, Peronospora spp, Phaeosphaeria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Phialophora spp, Phoma spp,
  • the compounds of formula (I) can also be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera,
  • Dictyoptera Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests.
  • Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests.
  • the pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fiber products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
  • the compounds of the invention may be used for example on turf, ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens, for example conifers, as well as for tree injection, pest management and the like.
  • Haematopinus spp. Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example,
  • Cimex spp. Distantiella theobroma, Dysdercus spp., Euchistus spp., Eurygaster spp., Lep- tocorisa spp., Nezara spp., Piesma spp., Rhodnius spp., Sahlbergella singularis, Scotino- phara spp. and Triatoma spp.;
  • Thysanoptera for example
  • Thysanura for example, Lepisma saccharina
  • nematodes for example root knot nematodes, stem eelworms and foliar nematodes;
  • Heterodera spp. for example Heterodera schachtii, Heterodora avenae and Heterodora trifolii
  • Globodera spp. for example Globodera rostochiensis
  • Meloidogyne spp. for example Meloidogyne incoginita and Meloidogyne javanica
  • Radopholus spp. for example Radopholus similis
  • Pratylenchus for example Pratylenchus neglectans and Pratylenchus penetrans
  • Tylenchulus for example Tylenchulus semipenetrans
  • cabbage seedpod weevil (Ceutorhynchus spp.).
  • the compounds of formula I can for example, be used for controlling, i. e. containing or destroying, animal pests of the abovementioned type which occur on useful plants in agriculture, in horticulture and in forests, or on organs of useful plants, such as fruits, flowers, foliage, stalks, tubers or roots, and in some cases even on organs of useful plants which are formed at a later point in time remain protected against these animal pests.
  • target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St.
  • perennial and annual crops such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries
  • cereals for example barley, maize (corn), millet, oats
  • Augustine grass and Zoysia grass herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber;
  • vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
  • the useful plants and / or target crops in accordance with the invention include conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties.
  • suitable genetically enhanced or engineered crop varieties include the Stoneville 5599BR cotton and Stoneville 4892BR cotton varieties.
  • useful plants and/or “target crops” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and
  • useful plants and/or target crops is to be understood as including those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include ⁇ -endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.
  • Vip vegetative insecticidal proteins
  • insecticidal proteins of bacteria colonising nematodes and toxins produced by scorpions, arachnids, wasps and fungi.
  • An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut® (Syngenta Seeds).
  • An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot® (Syngenta Seeds).
  • Crops or seed material thereof can also be resistant to multiple types of pests (so- called stacked transgenic events when created by genetic modification).
  • a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).
  • useful plants and/or “target crops” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called “pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392 225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191 .
  • locus as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • plant propagation material is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material” is understood to denote seeds.
  • Pesticidal agents referred to herein using their common name are known, for example, from “The Pesticide Manual”, 15th Ed., British Crop Protection Council 2009.
  • the compounds of formula I may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
  • Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.
  • Such carriers are for example described in WO 97/33890.
  • the compounds of formula I are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds.
  • further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non-selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
  • the compounds of formula I may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula I or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
  • the invention provides a composition, preferably a fungicidal composition, comprising at least one compound formula I an agriculturally acceptable carrier and optionally an adjuvant.
  • An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use.
  • Agricultural carriers are well known in the art.
  • said composition may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula I.
  • the compound of formula (I) may be the sole active ingredient of a composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate.
  • An additional active ingredient may, in some cases, result in unexpected synergistic activities.
  • Suitable additional active ingredients include the following acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, , dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine
  • Suitable additional active ingredients also include the following: 3- difluoromethyl-1 -methyl-1 H-pyrazole-4-carboxylic acid (9-dichloromethylene-1 ,2,3,4- tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide , 3-difluoromethyl-1 -methyl-1 H-pyrazole-4- carboxylic acid methoxy-[1 -methyl-2-(2,4,6-trichlorophenyl)-ethyl]-amide , 1 -methyl-3- difluoromethyl-1 H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1 -methyl-indan-4- yl)-amide (1072957-71 -1 ), 1 -methyl-3-difluoromethyl-1 H-pyrazole-4-carboxylic acid (4'- methylsulfanyl-biphenyl-2-yl)-amide, 1 -methyl-3-diflu
  • prothiocarb prothioconazole, pyracarbolid, pyraclostrobin, pyrametrostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinacetol, quinazamid, quinconazole, quinomethionate, quinoxyfen, quintozene, rabenzazole,
  • the compounds of the invention may also be used in combination with anthelmintic agents.
  • anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP-444964 and EP-594291 .
  • Additional anthelmintic agents include
  • Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
  • the compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE- 19520936.
  • the compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO- 9615121 and also with anthelmintic active cyclic depsipeptides such as those described in WO-961 1945, WO-9319053, WO- 9325543, EP-626375, EP-382173, WO-9419334, EP- 382173, and EP-503538.
  • the compounds of the invention may be used in combination with other compounds
  • ectoparasiticides for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like;
  • neonicotinoids such as imidacloprid and the like.
  • the compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers
  • Organophosphates acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, me
  • Carbamates alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb,
  • furathiocarb, HCN-801 isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m- cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
  • Arthropod growth regulators a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox,
  • tebufenozide a compound selected from the group consisting of S-methoprene and S-methoprene.
  • juvenoids pyriproxyfen, methoprene (including S-methoprene), fenoxycarb;
  • lipid biosynthesis inhibitors spirodiclofen.
  • camphechlor cartap
  • chlorobenzilate chlordimeform
  • chlorfenapyr chromafenozide
  • clothianidine cyromazine
  • diacloden diafenthiuron
  • DBI-3204 dinactin
  • protrifenbute protrifenbute, pymethrozine, pyridaben, pyrimidifen, NC-1 1 1 1 , R-195,RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601 , silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301 .
  • Biological agents Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
  • Bactericides chlortetracycline, oxytetracycline, streptomycin.
  • Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal or insecticidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by insects or by phytopathogenic
  • microorganisms preferably fungal organisms.
  • a further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a preferred individual compound as above-defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
  • Controlling or preventing means reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
  • a preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect.
  • the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation e.g. a composition containing the compound of formula I, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha.
  • convenient dosages are from 10mg to 1 g of active substance per kg of seeds.
  • rates of 0.001 to 50 g of a compound of formula I per kg of seed preferably from 0.01 to 10g per kg of seed are generally sufficient.
  • compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK
  • compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects).
  • appropriate formulation inerts diiluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects.
  • conventional slow release formulations may be employed where long lasting efficacy is intended.
  • Particularly formulations to be applied in spraying forms such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g.
  • a seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • suitable seed dressing formulation form e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • seed dressing formulations are known in the art.
  • Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
  • the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula I together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like.
  • Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent.
  • Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.
  • Example 1 This example illustrates the preparation of N-(1 ,1 -dimethyl-2-morpholino-2-oxo- ethyl)-2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carboxamide (Compound l.ad.464) a) Preparation of 2-isopropoxy-2-phenyl-ethanol
  • hexafluorophosphate (884 mg, 2.21 mmol), N-ethyl-N-isopropyl-propan-2-amine (476 mg, 3.68 mmol), 5-bromo-2-(2-isopropoxy-2-phenyl-ethoxy)pyridine-3-carboxylic acid (700 mg, 1 .84 mmol) were mixed together in dimethylformamide (18 ml) and the reaction mixture was stirred at room temperature for 2 hours before it was quenched with an aqueous saturated solution of NaHC0 3 (30 ml). The aqueous phase was extracted with ethyl acetate (50 ml) and the organic phase was concentrated under reduced pressure.
  • the reaction was monitored by UPLC. Fresh tetrakis(triphenylphosphine)palladium(0) was then added and the reaction mixture was stir for a further 2 hours at 130 °C. The reaction mixture was then cooled down to ambient temperature, concentrated under reduced pressure, taken up with ethyl acetate (50 ml) and washed thorough twice with aqueous sodium hydroxide (1 N, 20 ml). The organic phase was concentrated under vacuum and absorbed onto isolute. A pad of 5 mm of KF powder was added on the loading cartridge.
  • the sample was therefore purified by flash chromatography on silica gel with a gradient of ethyl acetate and cyclohexane to give tert-butyl 2-[[2-(2- isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carbonyl]amino]-2-methyl-propanoate.
  • Table 1 illustrates examples of individual compounds of formula I according to the invention.
  • R 1 , R 2 , R 3 , X 1 , X 3 , X 4 and L 1 are as defined in Table 1 .
  • active ingredient denoting a mixture of compound I and compounds of component (B+C) in a specific mixing ratio.
  • LC/MS Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the method is: (ACQUITY UPLC from Waters, Phenomenex Gemini C18, 3 ⁇ particle size, 1 10 Angstrom, 30 x 3 mm column, 1 .7mL/min., 60 °C, H 2 0 + 0.05% HCOOH (95%) / CH 3 CN/MeOH 4:1 + 0.04% HCOOH (5%) - 2 min.
  • Wettable powders a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % sodium lignosulfonate 5 % 5 %
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
  • Powders for drv seed treatment a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % -
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
  • Emulsions of any required dilution which can be used in plant protection, can be obtained from this concentrate by dilution with water.
  • Active ingredient [compound of formula (I)] 5 % 6 % 4 % talcum 95 %
  • Ready-for-use dusts are obtained by mixing active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders also be used for dry dressings for seed.

Abstract

Compounds of the formula (I), wherein the substituents are as defined in claim 1, are useful as a pesticides.

Description

Microbiocidal Heterocyclic Derivatives
The present invention relates to microbiocidal heterobicyclic derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity. The invention also relates to preparation of these heterobicyclic derivatives, to heterobicyclic derivatives used as intermediates in the preparation of these heterobicyclic derivatives, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the heterobicyclic derivatives, to preparation of these compositions and to use of the
heterobicyclic derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.
Certain compounds for use as fungicides are described in WO 2013/071169.
The present invention provides compounds of formula I:
Figure imgf000002_0001
wherein,
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl, C2-C6alkynyl or C3-C6cycloalkyl in which the alkyl, alkynyl and cycloalkyl groups are optionally substituted by one or more R6;
R2 is heterocyclyl, which can be optionally substituted by one or more R6;
R3 is -C(=0)R6, -S(=0)R6, -S(=0)2R6 or heterocyclyl, which can be optionally substituted by one or more R6;
R4 is C2-C6alkynyl, C3-C6cycloalkyl, aryl or heterocyclyl, in which the alkynyl, cycloalkyl, aryl and heterocyclyl groups are optionally substituted by one or more R6;
R5 is hydrogen, CrC6alkyl, CrC6alkoxy, C2-C6alkenyl, C2-C6alkenyloxy, C2-C6alkynyl, C2- C6alkynyloxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy or aryl, in which the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and aryl groups are optionally substituted by one or more R6;
R6 is hydrogen, halogen, cyano, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6alkenylthio, C2-C6haloalkenyloxy, C2-C6haloalkenylthio, C2-C6alkynyl, C2- C6alkynyloxy, C2-C6alkynylthio, C3-C6cycloalkyl, C3-C6halocycloalkyl, C3-C6cycloalkyloxy, C3- C6cycloalkylthio, C3-C6halocycloalkyloxy, C3-C6halocycloalkylthio, -NH(CrC6alkyl), -N(Ci- C6alkyl)2, -NH(C C6haloalkyl), -N(C C6haloalkyl)2, -NH(C2-C6alkenyl), -N(C2-C6alkenyl)2, - NH(C2-C6 aloalkenyl), -N(C2-C6 aloalkenyl)2! -NH(C2-C6alkynyl), -N(C2-C6alkynyl)2, -NH(C3- Cecycloalkyl), -N(C3-C6cycloalkyl)2, -NH(C3-C6 alocycloalkyl), -N(C3-C6 alocycloalkyl)2, -
Figure imgf000003_0001
C6 aloalkyl))2,
Figure imgf000003_0002
Ce aloalkoxy),
Figure imgf000003_0003
-NHC(=0)(C2-C6alkenyl), -N(C(=0)(C2- C6alkenyl))2, -NHC(=0)(C2-C6 aloalkenyl), -N(C(=0)(C2-C6 aloalkenyl))2, -NHC(=0)(C2- C6alkenyloxy), -N(C(=0)(C2-C6alkenyloxy))2, -NHC(=0)(C2-C6 aloalkenyloxy), -N(C(=0)(C2- C6 aloalkenyloxy))2, -NHC(=0)(C2-C6alkynyl), -N(C(=0)(C2-C6alkynyl))2, -NHC(=0)(C2- C6alkynyloxy), -N(C(=0)(C2-C6alkynyloxy))2, -NHC(=0)(C3-C6cycloalkyl), -N(C(=0)(C3- C6cycloalkyl))2, -NHC(=0)(C3-C6 alocycloalkyl), -N(C(=0)(C3-C6 alocycloalkyl))2, - NHC(=0)(C3-C6cycloalkyloxy), -N(C(=0)(C3-C6cycloalkyloxy))2, -NHC(=0)(C3- Ce alocycloalkyloxy), -N(C(=0)(C3-C6 alocycloalkyloxy))2, -OC(=0)(CrC6alkyl), -OC(=0)(C C6 aloalkyl), -OC(=0)(Ci-C6alkoxy),
Figure imgf000003_0004
-OC(=0)(C2-C6alkenyl), - OC(=0)(C2-C6 aloalkenyl), -OC(=0)(C2-C6alkenyloxy), -OC(=0)(C2-C6 aloalkenyloxy), - OC(=0)(C2-C6alkynyl), -OC(=0)(C2-C6alkynyloxy), -OC(=0)(C3-C6cycloalkyl), -OC(=0)(C3- Ce alocycloalkyl), -OC(=0)(C3-C6cycloalkyloxy), -OC(=0)(C3-C6 alocycloalkyloxy), - C(=0)(CrC6alkyl), -C(=0)(Ci-C6haloalkyl),
Figure imgf000003_0005
- C(=0)(C2-C6alkenyl), -C(=0)(C2-C6 aloalkenyl), -C(=0)(C2-C6alkenyloxy), -C(=0)(C2- C6 aloalkenyloxy), -C(=0)(C2-C6alkynyl), -C(=0)(C2-C6alkynyloxy), -C(=0)(C3-C6cycloalkyl), - C(=0)(C3-C6 alocycloalkyl), -C(=0)(C3-C6cycloalkyloxy), -C(=0)(C3-C6 alocycloalkyloxy), - S(=0)2(Ci-C6alkyl),
Figure imgf000003_0006
-S(=0)2(Ci-C6alkoxy),
-S(=0)2(C2-C6alkenyl), -S(=0)2(C2-C6 aloalkenyl), -S(=0)2(C2-C6alkenyloxy), -S(=0)2(C2- C6 aloalkenyloxy), -S(=0)2(C2-C6alkynyl), -S(=0)2(C2-C6alkynyloxy), -S(=0)2(C3- Cecycloalkyl), -S(=0)2(C3-C6 alocycloalkyl), -S(=0)2(C3-C6cycloalkyloxy), -S(=0)2(C3- Ce alocycloalkyloxy),
Figure imgf000003_0007
Ce aloalkyl),
Figure imgf000003_0008
Figure imgf000003_0009
-NHS(=0)2(C2-C6alkenyl), - N(S(=0)2(C2-C6alkenyl))2, -NHS(=0)2(C2-C6 aloalkenyl), -N(S(=0)2(C2-C6 aloalkenyl))2, - NHS(=0)2(C2-C6alkenyloxy), -N(S(=0)2(C2-C6alkenyloxy))2, -NHS(=0)2(C2-C6 aloalkenyloxy), -N(S(=0)2(C2-C6 aloalkenyloxy))2, -NHS(=0)2(C2-C6alkynyl), -N(S(=0)2(C2-C6alkynyl))2, - NHS(=0)2(C2-C6alkynyloxy), -N(S(=0)2(C2-C6alkynyloxy))2, -NHS(=0)2(C3-C6cycloalkyl), - N(S(=0)2(C3-C6cycloalkyl))2, -NHS(=0)2(C3-C6 alocycloalkyl), -N(S(=0)2(C3- C6 alocycloalkyl))2, -NHS(=0)2(C3-C6cycloalkyloxy), -N(S(=0)2(C3-C6cycloalkyloxy))2, - NHS(=0)2(C3-C6 alocycloalkyloxy), -N(S(=0)2(C3-C6 alocycloalkyloxy))2, -CH(=NOC
Cealkyl), -C(=NO(Ci-C6alkyl))Ci-C6alkyl, -C(=NO(Ci-C6alkyl))C2-C6alkenyl, -C(=NO(C
C6alkyl))C2-C6alkynyl, -C(=NO(Ci-C6alkyl))C3-C6cycloalkyl, -CH(=NN(Ci-C6alkyl)2, - C(=NN(Ci-C6alkyl)2)Ci-C6alkyl, -C(=NN(Ci-C6alkyl)2)C2-C6alkenyl, -C(=NN(CrC6alkyl)2)C2- C6alkynyl, -C(=NN(Ci-C6alkyl)2)C3-C6cycloalkyl, aryl or heterocyclyl; or two R6 linked to the same carbon atom can form a saturated 3- to 4-membered carbocyclic or heterocyclic ring;
L1 and L2 are independently a direct bond, -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2- z, -NR5-z, -NR5-C(R6)2-z, -C(R6)2-NR5-z, -NR5-C(R6)2-C(R6)2-z, -C(R6)2-NR5-C(R6)2-z, -C(R6)2- C(R6)2-NR5-z, -C(R6)2-0-z, -C(R6)2-0-C(R6)2-z, -C(R6)2-C(R6)2-0-z, in each case z indicates the bond that is connected to R3 or R4;
or a salt or a N-oxide thereof.
Where substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents, e.g. one to three substituents. Normally not more than three such optional substituents are present at the same time. Where a group is indicated as being substituted, e.g. alkyl, this includes those groups that are part of other groups, e.g. the alkyl in alkylthio.
The term "halogen" refers to fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
Alkyl substituents may be straight-chained or branched. Alkyl on its own or as part of another substituent is, depending upon the number of carbon atoms mentioned, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso- propyl, iso-butyl, sec-butyl, tert-butyl or iso-amyl.
Alkenyl substituents can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Examples are vinyl and allyl. The alkenyl groups are preferably C2-C6, more preferably C2-C4 and most preferably C2-C3 alkenyl groups.
Alkynyl substituents can be in the form of straight or branched chains. Examples are ethynyl and propargyl. The alkynyl groups are preferably C2-C6, more preferably C2-C4 and most preferably C2-C3 alkynyl groups.
Haloalkyl groups may contain one or more identical or different halogen atoms and, for example, may stand for CH2CI, CHCI2, CCI3, CH2F, CHF2, CF3, CF3CH2, CH3CF2, CF3CF2 or CCI3CCI2.
Haloalkenyl groups are alkenyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 2,2-difluorovinyl or 1 ,2- dichloro-2-fluoro-vinyl.
Haloalkynyl groups are alkynyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 1 -chloro-prop-2-ynyl.
Alkoxy means a radical -OR, where R is alkyl, e.g. as defined above. Alkoxy groups include, but are not limited to, methoxy, ethoxy, 1 -methylethoxy, propoxy, butoxy, 1 - methylpropoxy and 2-methylpropoxy.
Cyano means a -CN group.
Amino means an -NH2 group. Hydroxyl or hydroxy stands for a -OH group.
Aryl means a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
Heterocyclyl stands for saturated, partially unsaturated and aromatic heterocyclic ring systems, which can be mono-, bi- or tricyclic and wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member, which can be accompanied by other oxygen, nitrogen, sulphur, C(=0), C(=S), C(=NR5), C(=NOR1), C(=NN(R5)2), S(=0) or S(=0)2 as ring members. Monocyclic and bicyclic aromatic ring systems are preferred. For example, monocyclic heteocyclyl may be a 4- to 7-membered ring containing one to three heteroatoms selected from oxygen, nitrogen and sulfur, more preferably selected from nitrogen and oxygen. Bicyclic heterocyclyl may be a 7- to 1 1 -membered bicyclic ring containing one to five heteroatoms, preferably one to three heteroatoms, selected from oxygen, nitrogen and sulfur. The different rings of bi- and tricyclic heterocyclyl may be linked via one atom belonging to two different rings (spiro), via two adjacent ring atoms belonging to two different rings (annelated) or via two different, not adjacent ring atoms belonging to two different rings (bridged). Examples for saturated heterocyclyl are azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, thiazolidinyl, isoxazolidinyl, isothiazolidinyl, oxadiazolidinyl, thiadiazolidinyl, dioxolanyl, dithiolanyl, piperidinyl, piperazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, dithianyl and morpholinyl. Examples for partially unsaturated heterocyclyl are pyrrolinyl, dihydrofuranyl, dihydrothienyl, pyrazolinyl, imidazolinyl, oxazolinyl, thiazolinyl, isoxazolinyl, isothiazinyl, oxadiazolinyl, thiadiazolinyl, dihydropyranyl, dihydrothiopyranyl, oxathiolyl and oxazinyl. Examples of aromatic heterocyclyl are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothiophenyl, benzofuranyl,
benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolinyl,
isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl.
Heterocyclyl rings do not contain adjacent oxygen ring atoms, adjacent sulfur ring atoms or adjacent oxygen and sulfur ring atoms. A link to a heterocyclyl group can be via a carbon atom or via a nitrogen atom.
The presence of one or more possible asymmetric carbon atoms in a compound of formula I means that the compounds may occur in optically isomeric forms, i.e. enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula I is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula I. Likewise, formula I is intended to include all possible tautomers. The present invention includes all possible tautomeric forms for a compound of formula I.
In each case, the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.
N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book "Heterocyclic N- oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
The following list provides definitions, including preferred definitions, for substituents X1, X2, X3, X4, R1, R2, R3, R4, L1 and L2 with reference to compounds of formula I. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3.
X1 is preferably S or CH=N.
X2 and X3 are independently O, S or NR5;
X2 is preferably O or S.
X3 is preferably O or NR5, more preferably O or NH.
X4 is O or NR5; more preferably O or NH.
R1 is hydrogen, CrC6alkyl, C2-C6alkynyl or C3-C6cycloalkyl in which the alkyl, alkynyl and cycloalkyl groups are optionally substituted by one or more R6.
Preferably R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyl groups are optionally substituted by one or more R6, more preferably hydrogen or CrC6alkyl, even more preferably methyl.
R2 is heterocyclyl, which can be optionally substituted by one or more R6;
Preferably R2 is a 5- to 6-membered aromatic heterocyclic ring system, more preferably 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl.
R3 is -C(=0)R6, -S(=0)R6, -S(=0)2R6 or heterocyclyl, which can be optionally substituted by one or more R6;
Preferably R3 is -C(=0)R6 or heterocyclyl, more preferably -C(=0)NH(C C6alkyl), - C(=0)N(Ci-C6alkyl)2 or -C(=0)heterocyclyl, even more preferably -C(=0)NH(C C6alkyl).
R4 is C2-C6alkynyl, C3-C6cycloalkyl, aryl or heterocyclyl, in which the alkynyl, cycloalkyl, aryl and heterocyclyl groups are optionally substituted by one or more R6.
Preferably R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyl, aryl and heterocyclyl are optionally substituted by one or more R6, more preferably aryl or 5- to 6- membered aromatic heterocyclic ring system, even more preferably phenyl or thienyl.
R5 is hydrogen, CrC6alkyl, CrC6alkoxy, C2-C6alkenyl, C2-C6alkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy or aryl, in which the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl and aryl groups are optionally substituted by one or more R6; Preferably R5 is hydrogen, CrC6alkyl, d-C6alkoxy; more preferably hydrogen or d- C6alkyl, even more preferably hydrogen or methyl.
R6 is hydrogen, halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, d- C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2- C6haloalkenyl, C2-C6alkenyloxy, C2-C6alkenylthio, C2-C6haloalkenyloxy, C2-C6haloalkenylthio, C2-C6alkynyl, C2-C6alkynyloxy, C2-C6alkynylthio, C3-C6cycloalkyl, C3-C6halocycloalkyl, C3- C6cycloalkyloxy, C3-C6cycloalkylthio, C3-C6halocycloalkyloxy, C3-C6halocycloalkylthio, - NH(CrC6alkyl), -N(C C6alkyl)2, -NH(C C6haloalkyl), -N(C C6haloalkyl)2, -NH(C2-C6alkenyl), -N(C2-C6alkenyl)2, -NH(C2-C6haloalkenyl), -N(C2-C6haloalkenyl)2, -NH(C2-C6alkynyl), -N(C2- C6alkynyl)2, -NH(C3-C6cycloalkyl), -N(C3-C6cycloalkyl)2, -NH(C3-C6halocycloalkyl), -N(C3- C6halocycloalkyl)2, -NHC(=0)(C C6alkyl), -N(C(=0)(CrC6alkyl))2, -NHC(=0)(C C6haloalkyl), N(C(=0)(CrC6haloalkyl))2, -NHC(=0)(C C6alkoxy), -N(C(=0)(CrC6alkoxy))2, -NHC(=0)(C Cehaloalkoxy), -N(C(=0)(CrC6haloalkoxy))2, -NHC(=0)(C2-C6alkenyl), -N(C(=0)(C2- C6alkenyl))2, -NHC(=0)(C2-C6haloalkenyl), -N(C(=0)(C2-C6haloalkenyl))2, -NHC(=0)(C2- C6alkenyloxy), -N(C(=0)(C2-C6alkenyloxy))2, -NHC(=0)(C2-C6haloalkenyloxy), -N(C(=0)(C2- C6haloalkenyloxy))2, -NHC(=0)(C2-C6alkynyl), -N(C(=0)(C2-C6alkynyl))2, -NHC(=0)(C2- C6alkynyloxy), -N(C(=0)(C2-C6alkynyloxy))2, -NHC(=0)(C3-C6cycloalkyl), -N(C(=0)(C3- C6cycloalkyl))2, -NHC(=0)(C3-C6halocycloalkyl), -N(C(=0)(C3-C6halocycloalkyl))2, - NHC(=0)(C3-C6cycloalkyloxy), -N(C(=0)(C3-C6cycloalkyloxy))2, -NHC(=0)(C3- Cehalocycloalkyloxy), -N(C(=0)(C3-C6halocycloalkyloxy))2, -OC(=0)(C C6alkyl), -OC(=0)(C C6haloalkyl), -OC(=0)(C C6alkoxy), -OC(=0)(C C6haloalkoxy), -OC(=0)(C2-C6alkenyl), - OC(=0)(C2-C6haloalkenyl), -OC(=0)(C2-C6alkenyloxy), -OC(=0)(C2-C6haloalkenyloxy), - OC(=0)(C2-C6alkynyl), -OC(=0)(C2-C6alkynyloxy), -OC(=0)(C3-C6cycloalkyl), -OC(=0)(C3- Cehalocycloalkyl), -OC(=0)(C3-C6cycloalkyloxy), -OC(=0)(C3-C6halocycloalkyloxy), - C(=0)(CrC6alkyl),
Figure imgf000007_0001
- C(=0)(C2-C6alkenyl), -C(=0)(C2-C6haloalkenyl), -C(=0)(C2-C6alkenyloxy), -C(=0)(C2- C6haloalkenyloxy), -C(=0)(C2-C6alkynyl), -C(=0)(C2-C6alkynyloxy), -C(=0)(C3-C6cycloalkyl), - C(=0)(C3-C6halocycloalkyl), -C(=0)(C3-C6cycloalkyloxy), -C(=0)(C3-C6halocycloalkyloxy), - S(=0)2(C C6alkyl), -S(=0)2(C C6haloalkyl), -S(=0)2(C C6alkoxy), -S(=0)2(C C6haloalkoxy), -S(=0)2(C2-C6alkenyl), -S(=0)2(C2-C6haloalkenyl), -S(=0)2(C2-C6alkenyloxy), -S(=0)2(C2- C6haloalkenyloxy), -S(=0)2(C2-C6alkynyl), -S(=0)2(C2-C6alkynyloxy), -S(=0)2(C3- Cecycloalkyl), -S(=0)2(C3-C6halocycloalkyl), -S(=0)2(C3-C6cycloalkyloxy), -S(=0)2(C3- Cehalocycloalkyloxy), -NHS(=0)2(C C6alkyl), -N(S(=0)2(CrC6alkyl))2, -NHS(=0)2(C
Cehaloalkyl), N(S(=0)2(CrC6haloalkyl))2, -NHS(=0)2(C C6alkoxy), -N(S(=0)2(CrC6alkoxy))2, -NHS(=0)2(CrC6haloalkoxy), -N(S(=0)2(CrC6haloalkoxy))2, -NHS(=0)2(C2-C6alkenyl), - N(S(=0)2(C2-C6alkenyl))2, -NHS(=0)2(C2-C6haloalkenyl), -N(S(=0)2(C2-C6haloalkenyl))2, - NHS(=0)2(C2-C6alkenyloxy), -N(S(=0)2(C2-C6alkenyloxy))2, -NHS(=0)2(C2-C6haloalkenyloxy), -N(S(=0)2(C2-C6haloalkenyloxy))2, -NHS(=0)2(C2-C6alkynyl), -N(S(=0)2(C2-C6alkynyl))2, - NHS(=0)2(C2-C6alkynyloxy), -N(S(=0)2(C2-C6alkynyloxy))2! -NHS(=0)2(C3-C6cycloalkyl), - N(S(=0)2(C3-C6cycloalkyl))2! -NHS(=0)2(C3-C6halocycloalkyl), -N(S(=0)2(C3- C6halocycloalkyl))2, -NHS(=0)2(C3-C6cycloalkyloxy), -N(S(=0)2(C3-C6cycloalkyloxy))2, - NHS(=0)2(C3-C6halocycloalkyloxy), -N(S(=0)2(C3-C6halocycloalkyloxy))2, -CH(=NOC
Cealkyl), -C(=NO(Ci-C6alkyl))Ci-C6alkyl, -C(=NO(Ci-C6alkyl))C2-C6alkenyl, -C(=NO(C C6alkyl))C2-C6alkynyl, -C(=NO(Ci-C6alkyl))C3-C6cycloalkyl, -CH(=NN(Ci-C6alkyl)2, - C(=NN(Ci-C6alkyl)2)Ci-C6alkyl, -C(=NN(Ci-C6alkyl)2)C2-C6alkenyl, -C(=NN(CrC6alkyl)2)C2- C6alkynyl, -C(=NN(Ci-C6alkyl)2)C3-C6cycloalkyl, aryl or heterocyclyl; or two R6 linked to the same carbon atom can form a saturated 3- to 4-membered carbocyclic or heterocyclic ring;
Preferably R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, d-
C6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2- C6haloalkenyl, C2-C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3- C6cycloalkyl, C3-C6halocycloalkyl, C3-C6cycloalkyloxy, C3-C6halocycloalkyloxy, more preferably halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2- C6alkenyl, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, even more preferably halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkynyl or C3- C6cycloalkyl, most preferably fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl.
L1 and L2 are independently a direct bond, -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2- C(R6)2-z, -NR5-z, -NR5-C(R6)2-z, -C(R6)2-NR5-z, -NR5-C(R6)2-C(R6)2-z, -C(R6)2-NR5-C(R6)2-z, - C(R6)2-C(R6)2-NR5-z, -C(R6)2-0-z, -C(R6)2-0-C(R6)2-z, -C(R6)2-C(R6)2-0-z, in each case z indicates the bond that is connected to R3 or R4.
L1 is preferably -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z, more preferably -C(R6)2-z or -C(R6)2-C(R6)2-z, even more preferably -C(CH3)2-z.
L2 is preferably -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or
-C(R6)2-0-z, more preferably -C(R6)2-C(R6)2-z or -C(R6)2-0-z, even more preferably - CH2CH(0(CrC6alkyl))-z.
Preferably the compound of formula I is a compound wherein:
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyl groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyl, aryl and heterocyclyl are optionally substituted by one or more R6; R5 is hydrogen, d-C6alkyl or CrC6alkoxy;
R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, Ci- Cehaloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3- C6halocycloalkyl, C3-C6cycloalkyloxy or C3-C6halocycloalkyloxy;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, CrC6alkyl or CrC6alkoxy;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkenyl,
C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen or CrC6alkyl;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)NH(CrC6alkyl), -C(=0)N(C C6alkyl)2 or -C(=0)heterocyclyl;
R4 is aryl or 5- to 6-membered aromatic heterocyclic ring system;
R5 is hydrogen or CrC6alkyl;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkynyl or C3-C6cycloalkyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z; L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
R3 is -C(=0)NH(CrC6alkyl);
R4 is phenyl or thienyl;
R5 is hydrogen or methyl;
R6 is fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z;
L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
R3 is -C(=0)NH(CrC6alkyl);
R4 is phenyl or thienyl;
R5 is hydrogen or methyl;
L1 is -C(CH3)2-z;
L2 is CH2CH(0(CrC6alkyl))-z;
or a salt or a N-oxide thereof.
Alternatively, the compound of formula I is a compound wherein:
X1 is S or CH=N;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl; R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, d-C6alkyl or CrC6alkoxy;
R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, C C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3- C6halocycloalkyl, C3-C6cycloalkyloxy or C3-C6halocycloalkyloxy;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z; or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is S or CH=N;
X2 is O or S;
X3 is O or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, CrC6alkyl or CrC6alkoxy;
R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, C C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3- C6halocycloalkyl, C3-C6cycloalkyloxy or C3-C6halocycloalkyloxy;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z; or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is S or CH=N;
X2 is O or S;
X3 is O or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl; R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, d-C6alkyl or CrC6alkoxy;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof. Preferably the compound of formula I is a compound wherein:
X1 is S or CH=N;
X2 is O or S;
X3 is O or NR5;
X4 is O or NR5;
R1 is hydrogen or CrC6alkyl;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)NH(CrC6alkyl), -C(=0)N(C C6alkyl)2 or -C(=0)heterocyclyl;
R4 is aryl or 5- to 6-membered aromatic heterocyclic ring system;
R5 is hydrogen or CrC6alkyl;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkynyl or C3-C6cycloalkyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z;
L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein:
X1 is S or CH=N;
X2 is O or S;
X3 is O or NH;
X4 is O or NH;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
R3 is -C(=0)NH(CrC6alkyl);
R4 is phenyl or thienyl;
R6 is fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z;
L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
Preferably the compound of formula I is a compound wherein: X1 is S or CH=N;
X2 s O or S;
X3 s O or NH;
X4 s O or NH;
R1 s methyl;
R2 s 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
R3 s -C(=0)NH(CrC6alkyl);
R4 s phenyl or thienyl;
s -C(CH3)2-z;
s CH2CH(0(CrC6alkyl))-z;
or a salt or a N-oxide thereof.
The invention also relates to compounds of formula l-a:
Figure imgf000013_0001
in which X1, X2, X3, X4, R2, R3, R4, L1 and L2 have the definitions as described for formula I. Preferred definitions of X1, X2, X3, X4, R2, R3, R4, L1 and L2 are as defined for formula I.
s to compounds of formula l-b:
Figure imgf000013_0002
wherein X1, X2, X3, X4, R1, R3, R4, L1 and L2 have the definition as described for formula I. Preferred definitions of X1, X2, X3, X4, R1, R3, R4, L1 and L2 are as defined for formula I.
The invention also relates to compounds of formula l-c:
Figure imgf000013_0003
in which X2, X3, X4, R1, R2, R3, R4, L1 and L2 have the definitions as described for formula I. Preferred definitions of X2, X3, X4, R1, R2, R3, R4, L1 and L2 are as defined for formula I.
The invention also relates to compounds of formula l-d:
Figure imgf000014_0001
in which X2, X3, X4, R1, R2, R3, R4, L1 and L2 have the definitions as described for formula I. Preferred definitions of X2, X3, X4, R1, R2, R3, R4, L1 and L2 are as defined for formula I.
The invention also relates to compounds of formula l-e:
Figure imgf000014_0002
in which X1, X2, X3, X4, R1, R2, R3, R4 and L2 have the definitions as described for formula I. Preferred definitions of X1, X2, X3, X4, R1, R2, R3, R4 and L2 are as defined for formula I.
to compounds of formula l-f:
Figure imgf000014_0003
in which X1, X2, X3, X4, R1, R2, R4, L1 and L2 have the definitions as described for formula I. Preferred definitions of X1, X2, X3, X4, R1, R2, R4, L1 and L2 are as defined for formula I.
es to compounds of formula l-g:
Figure imgf000014_0004
in which X1, X2, X3, X4, R1, R2, R3, R4 and L1 have the definitions as described for formula I. Preferred definitions of X1, X2, X3, X4, R1, R2, R3, R4 and L1 are as defined for formula I.
The invention also relates to compounds of formula l-h:
Figure imgf000015_0001
in which X1, X2, X3, X4, R1, R2, R3, L1 and L2 have the definitions as described for formula I. Preferred definitions of X1, X2, X3, X4, R1, R2, R3, L1 and L2 are as defined for formula I. Compounds of the present invention can be made as shown in the following schemes, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).
The compounds of formula 1-1 , wherein X1, X2, X3, R1, R2, R3, R4, L1 and L2 are as defined for formula I can be obtained by transformation of a compound of formula II, wherein X1, X2, X3, R1, R2, R4 and L2 are as defined for formula I with a compound of formula III, wherein R3 and L1 are as defined for formula I and a peptide coupling reagent, such as BOP, EDCI or HOAT, and a base. This is shown in Scheme 1 .
Scheme 1
Figure imgf000015_0002
Alternatively, the compounds of formula 1-1 , wherein X1, X2, X3, R1, R2, R3, R4, L1 and L2 are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein X1, X2, X3, R1, R2, R4 and L2 are as defined for formula I with a compound of formula III, wherein R3 and L1 are as defined for formula I, and a base, such as pyridine or triethylamine. This is shown in Scheme 2.
Scheme 2
Figure imgf000015_0003
The compounds of formula I-2, wherein X1, X2, X3, R1, R2, R3, R4, L1 and L2 are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein X1, X2, X3, R1, R2, R4 and L2 are as defined for formula I with a compound of formula V, wherein R3 and L1 are as defined for formula I, and a base, such as pyridine or triethylamine. This is shown in Scheme 3.
Scheme 3
Figure imgf000016_0001
The compounds of formula IV, wherein X1, X2, X3, R1, R2, R4 and L2 are as defined for formula I can be obtained by transformation of a compound of formula II, wherein X1, X2, X3, R1, R2, R4 and L2 are as defined for formula I with a chlorination reagent, such as oxalyl chloride, thionyl chloride or phosphoryl chloride. This is shown in Scheme 4.
Scheme 4
Figure imgf000016_0002
Alternatively, the compounds of formula I, wherein X1, X2, X3, X4, R1, R2, R3, R4, L1 and L2 are as defined for formula I can be obtained by transformation of a compound of formula VI, wherein X1, X2, X3, X4, R1, R2, R3 and L1 are as defined for formula I with a compound of formula VII, wherein R4 and L2 are as defined for formula I and R7 is halogen, preferably chloro or bromo, or a sulfonate, preferably a mesylate or tosylate, and a base. This is shown in Scheme 5.
Scheme 5
Figure imgf000016_0003
Surprisingly, it has now been found that the novel compounds of formula I have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.
The compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants. The compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.
It is also possible to use compounds of formula I as fungicide. The term "fungicide" as used herein means a compound that controls, modifies, or prevents the growth of fungi. The term "fungicidally effective amount" means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil. The propagation material can be treated with a composition comprising a compound of formula I before planting: seed, for example, can be dressed before being sown. The active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
Furthermore the compounds according to present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management.
In addition, the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
The compounds of formula I are for example, effective against Fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses. These Fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses are for example:
Absidia corymbifera, Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terrus, Aureobasidium spp.
including A. pullulans, Blastomyces dermatitidis, Blumeria graminis, Bremia lactucae, Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. inclusing B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. tropicalis, Cephaloascus fragrans, Ceratocystis spp, Cercospora spp. including C.
arachidicola, Cercosporidium personatum, Cladosporium spp, Claviceps purpurea,
Coccidioides immitis, Cochliobolus spp, Colletotrichum spp. including C. musae,
Cryptococcus neoformans, Diaporthe spp, Didymella spp, Drechslera spp, Elsinoe spp, Epidermophyton spp, Erwinia amylovora, Erysiphe spp. including E. cichoracearum,
Eutypa lata, Fusarium spp. including F. culmorum, F. graminearum, F. langsethiae, F.
moniliforme, F. oxysporum, F. proliferatum, F. subglutinans, F. solani, Gaeumannomyces graminis, Gibberella fujikuroi, Gloeodes pomigena, Gloeosporium musarum, Glomerella cingulate, Guignardia bidwellii, Gymnosporangium juniperi-virginianae, Helminthosporium spp, Hemileia spp, Histoplasma spp. including H. capsulatum, Laetisaria fuciformis,
Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale, Microsporum spp, Monilinia spp, Mucor spp, Mycosphaerella spp. including M. graminicola, M. pomi, Oncobasidium theobromaeon, Ophiostoma piceae, Paracoccidioides spp,
Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P. philippinensis and P. sorghi, Peronospora spp, Phaeosphaeria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Phialophora spp, Phoma spp,
Phomopsis viticola, Phytophthora spp. including P. infestans, Plasmopara spp. including P. halstedii, P. viticola, Pleospora spp., Podosphaera spp. including P. leucotricha, Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas spp, Pseudoperonospora spp. including P. cubensis, P. humuli, Pseudopeziza tracheiphila, Puccinia Spp. including P. hordei, P. recondita, P. striiformis, P. triticina, Pyrenopeziza spp, Pyrenophora spp, Pyricularia spp. including P. oryzae, Pythium spp. including P. ultimum, Ramularia spp, Rhizoctonia spp, Rhizomucor pusillus, Rhizopus arrhizus, Rhynchosporium spp, Scedosporium spp. including S. apiospermum and S. prolificans, Schizothyrium pomi, Sclerotinia spp, Sderotium spp, Septoria spp, including S. nodorum, S. tritici, Sphaerotheca macularis, Sphaerotheca fusca (Sphaerotheca fuliginea), Sporothorix spp, Stagonospora nodorum, Stemphylium spp,. Stereum hirsutum, Thanatephorus cucumeris, Thielaviopsis basicola, Tilletia spp, Trichoderma spp. including T. harzianum, T. pseudokoningii, T. viride, Trichophyton spp, Typhula spp, Uncinula necator, Urocystis spp, Ustilago spp, Venturia spp. including V. inaequalis, Verticillium spp, and Xanthomonas spp.
The compounds of formula (I) can also be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Hemiptera, Thysanoptera, Orthoptera,
Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarines, nematodes and molluscs are hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fiber products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fruit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
The compounds of the invention may be used for example on turf, ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens, for example conifers, as well as for tree injection, pest management and the like.
Examples of the abovementioned animal pests are:
from the order Acarina, for example,
Acarus siro, Aceria sheldoni, Aculus schlechtendali, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Calipitrimerus spp., Chorioptes spp., Derma- nyssus gallinae, Eotetranychus carpini, Eriophyes spp., Hyalomma spp., Ixodes spp., Oly- gonychus pratensis, Ornithodoros spp., Panonychus spp., Phyllocoptruta oleivora, Polypha- gotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Tarsonemus spp. and Tetranychus spp.;
from the order Anoplura, for example,
Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; from the order Coleoptera, for example,
Agriotes spp., Anthonomus spp., Atomaria linearis, Chaetocnema tibialis, Cosmopolites spp., Curculio spp., Dermestes spp., Diabrotica spp., Epilachna spp., Eremnus spp., Leptinotarsa decemlineata, Lissorhoptrus spp., Melolontha spp., Orycaephilus spp., Otiorhynchus spp., Phlyctinus spp., Popillia spp., Psylliodes spp., Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp., Tenebrio spp., Tribolium spp. and Trogoderma spp.;
from the order Diptera, for example,
Aedes spp., Antherigona soccata, Bibio hortulanus, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Drosophila melanogaster, Fannia spp., Gastrophilus spp., Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Rhagoletis pomonella, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.;
from the order Heteroptera, for example,
Cimex spp., Distantiella theobroma, Dysdercus spp., Euchistus spp., Eurygaster spp., Lep- tocorisa spp., Nezara spp., Piesma spp., Rhodnius spp., Sahlbergella singularis, Scotino- phara spp. and Triatoma spp.;
from the order Homoptera, for example,
Aleurothrixus floccosus, Aleyrodes brassicae, Aonidiella spp., Aphididae, Aphis spp., Aspi- diotus spp., Bemisia tabaci, Ceroplaster spp., Chrysomphalus aonidium, Chrysomphalus dictyospermi, Coccus hesperidum, Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Laodelphax spp., Lecanium corni, Lepidosaphes spp., Macrosiphus spp., Myzus spp., Nephotettix spp., Nilaparvata spp., Parlatoria spp., Pemphigus spp., Planococ- cus spp., Pseudaulacaspis spp., Pseudococcus spp., Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Rhopalosiphum spp., Saissetia spp., Scaphoideus spp., Schizaphis spp., Sitobion spp., Trialeurodes vaporariorum, Trioza erytreae and Unaspis citri;
from the order Hymenoptera, for example,
Acromyrmex, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplo- campa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Solenopsis spp. and Vespa spp.;
from the order Isoptera, for example,
Reticulitermes spp.;
from the order Lepidoptera, for example,
Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyrotaenia spp., Autographa spp., Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Clysia ambi- guella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Crocidolomia binotalis, Cryptophlebia leucotreta, Cydia spp., Diatraea spp., Diparopsis castanea, Earias spp., Ephestia spp., Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Gra- pholita spp., Hedya nubiferana, Heliothis spp., Hellula undalis, Hyphantria cunea, Keiferia lycopersicella, Leucoptera scitella, Lithocollethis spp., Lobesia botrana, Lymantria spp., Ly- onetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Operophtera spp., Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis flammea, Pectinophora gossypi- ela, Phthorimaea operculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp., Scir- pophaga spp., Sesamia spp., Sparganothis spp., Spodoptera spp., Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni and Yponomeuta spp.;
from the order Mallophaga, for example,
Damalinea spp. and Trichodectes spp.;
from the order Orthoptera, for example,
Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Periplaneta spp. and Schistocerca spp.;
from the order Psocoptera, for example,
Liposcelis spp.;
from the order Siphonaptera, for example,
Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis;
from the order Thysanoptera, for example,
Frankliniella spp., Hercinothrips spp., Scirtothrips aurantii, Taeniothrips spp., Thrips palmi and Thrips tabaci;
from the order Thysanura, for example, Lepisma saccharina;
nematodes, for example root knot nematodes, stem eelworms and foliar nematodes;
especially Heterodera spp., for example Heterodera schachtii, Heterodora avenae and Heterodora trifolii; Globodera spp., for example Globodera rostochiensis; Meloidogyne spp., for example Meloidogyne incoginita and Meloidogyne javanica; Radopholus spp., for example Radopholus similis; Pratylenchus, for example Pratylenchus neglectans and Pratylenchus penetrans; Tylenchulus, for example Tylenchulus semipenetrans; Longidorus, Trichodorus, Xiphinema, Ditylenchus, Aphelenchoides and Anguina;
crucifer flea beetles (Phyllotreta spp.);
root maggots (Delia spp.) and
cabbage seedpod weevil (Ceutorhynchus spp.).
The compounds of formula I can for example, be used for controlling, i. e. containing or destroying, animal pests of the abovementioned type which occur on useful plants in agriculture, in horticulture and in forests, or on organs of useful plants, such as fruits, flowers, foliage, stalks, tubers or roots, and in some cases even on organs of useful plants which are formed at a later point in time remain protected against these animal pests.
Within the scope of present invention, target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St.
Augustine grass and Zoysia grass; herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber;
vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
The useful plants and / or target crops in accordance with the invention include conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties. By way of example, suitable genetically enhanced or engineered crop varieties include the Stoneville 5599BR cotton and Stoneville 4892BR cotton varieties.
The term "useful plants" and/or "target crops" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola).
Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and
LibertyLink®.
The term "useful plants" and/or "target crops" is to be understood as including those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include δ-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi. An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut® (Syngenta Seeds). An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot® (Syngenta Seeds). Crops or seed material thereof can also be resistant to multiple types of pests (so- called stacked transgenic events when created by genetic modification). For example, a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).
The term "useful plants" and/or "target crops" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191 . The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. The term "locus" as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
The term "plants" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.
Pesticidal agents referred to herein using their common name are known, for example, from "The Pesticide Manual", 15th Ed., British Crop Protection Council 2009.
The compounds of formula I may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
Suitable carriers and adjuvants, e.g. for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
The compounds of formula I are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non-selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation. The compounds of formula I may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula I or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
The invention provides a composition, preferably a fungicidal composition, comprising at least one compound formula I an agriculturally acceptable carrier and optionally an adjuvant. An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art. Preferably said composition may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula I.
The compound of formula (I) may be the sole active ingredient of a composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may, in some cases, result in unexpected synergistic activities.
Examples of suitable additional active ingredients include the following acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, , dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorous fungicides, organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.
Examples of suitable additional active ingredients also include the following: 3- difluoromethyl-1 -methyl-1 H-pyrazole-4-carboxylic acid (9-dichloromethylene-1 ,2,3,4- tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide , 3-difluoromethyl-1 -methyl-1 H-pyrazole-4- carboxylic acid methoxy-[1 -methyl-2-(2,4,6-trichlorophenyl)-ethyl]-amide , 1 -methyl-3- difluoromethyl-1 H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1 -methyl-indan-4- yl)-amide (1072957-71 -1 ), 1 -methyl-3-difluoromethyl-1 H-pyrazole-4-carboxylic acid (4'- methylsulfanyl-biphenyl-2-yl)-amide, 1 -methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy-1 -methyl-ethyl]-amide, (5-Chloro-2,4-dimethyl-pyridin-3- yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, (5-Bromo-4-chloro-2-methoxy-pyridin-3- yl)-(2!3,4-trimethoxy-6-methyl-phenyl)-methanone! 2-{2-[(E)-3-(2,6-Dichloro-phenyl)-1 - methyl-prop-2-en-(E)-ylideneaminooxymethyl]-phenyl}-2-[(Z)-methoxyimino]-N-methyl- acetamide, 3-[5-(4-Chloro-phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine, (E)-N-methyl-2- [2- (2, 5-dimethylphenoxymethyl) phenyl]-2-methoxy-iminoacetamide, 4-bromo-2-cyano-N, N-dimethyl-6-trifluoromethylbenzimidazole-1 -sulphonamide, a- [N-(3-chloro-2, 6-xylyl)-2- methoxyacetamido]-y-butyrolactone, 4-chloro-2-cyano-N, - dimethyl-5-p-tolylimidazole-1 - sulfonamide, N-allyl-4, 5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide, N- (l-cyano-1 , 2- dimethylpropyl)-2- (2, 4-dichlorophenoxy) propionamide, N- (2-methoxy-5-pyridyl)- cyclopropane carboxamide, (.+-.)-cis-1 -(4-chlorophenyl)-2-(1 H-1 ,2,4-triazol-1 -yl)- cycloheptanol, 2-(1 -tert-butyl)-1 -(2-chlorophenyl)-3-(1 ,2,4-triazol-1 -yl)-propan-2-ol, 2',6'- dibromo-2-methyl-4-trifluoromethoxy-4'-trifluoromethyl-1 ,3-thiazole- 5-carboxanilide, 1 - imidazolyl-1 -(4'-chlorophenoxy)-3,3-dimethylbutan-2-one, methyl (E)-2-[2-[6-(2- cyanophenoxy)pyrimidin-4-yloxy]phenyl]3-methoxyacrylate, methyl (E)-2-[2-[6-(2- thioamidophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylat e, methyl (E)-2-[2-[6-(2- fluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2,6- difluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacryla te, methyl (E)-2-[2-[3-(pyrimidin- 2-yloxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(5-methylpyrimidin-2-yloxy)- phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(phenyl- sulphonyloxy)phenoxy]phenyl-3-methoxyacrylate, methyl (E)-2-[2-[3-(4- nitrophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-phenoxyphenyl]-3- methoxyacrylate, methyl (E)-2-[2-(3,5-dimethyl-benzoyl)pyrrol-1 -yl]-3-methoxyacrylate, methyl (E)-2-[2-(3-methoxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2[2-(2- phenylethen-1 -yl)-phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dichlorophenoxy)pyridin-3- yl]-3-methoxyacrylate, methyl (E)-2-(2-(3-(1 ,1 ,2,2-tetrafluoroethoxy)phenoxy)phenyl)-3- methoxyacrylate, methyl (E)-2-(2-[3-(alpha-hydroxybenzyl)phenoxy]phenyl)-3- methoxyacrylate, methyl (E)-2-(2-(4-phenoxypyridin-2-yloxy)phenyl)-3-methoxyacrylate, methyl (E)-2-[2-(3-n-propyloxy-phenoxy)phenyl]3-methoxyacrylate, methyl (E)-2-[2-(3- isopropyloxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(2- fluorophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3- ethoxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(4-tert-butyl-pyridin-2- yloxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(3-cyanophenoxy)phenoxy]phenyl]-3- methoxyacrylate, methyl (E)-2-[2-[(3-methyl-pyridin-2-yloxymethyl)phenyl]-3- methoxyacrylate, methyl (E)-2-[2-[6-(2-methyl-phenoxy)pyrimidin-4-yloxy]phenyl]-3- methoxyacrylate, methyl (E)-2-[2-(5-bromo-pyridin-2-yloxymethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3-(3-iodopyridin-2-yloxy)phenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2- [2-[6-(2-chloropyridin-3-yloxy)pyrimidin-4-yloxy]phenyl]-3-methoxyac rylate, methyl (E),(E)-2- [2-(5,6-dimethylpyrazin-2-ylmethyloximinomethyl)phenyl]-3-methox yacrylate, methyl (E)-2- {2-[6-(6-methylpyridin-2-yloxy)pyrimidin-4-yloxy]phenyl}-3-methoxy-a crylate, methyl (E),(E)- 2-{ 2-(3-methoxyphenyl)methyloximinomethyl]-phenyl}-3-methoxyacrylate, methyl (E)-2-{2-(6- (2-azidophenoxy)-pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[6- phenylpyrimidin-4-yl)-methyloximinomethyl]phenyl}-3-methox yacrylate, methyl (E),(E)-2-{2- [(4-chlorophenyl)-methyloximinomethyl]-phenyl}-3-methoxyacryl ate, methyl (E)-2-{2-[6-(2-n- propylphenoxy)-1 ,3,5-triazin-4-yloxy]phenyl}-3-methoxyacr ylate, methyl (E),(E)-2-{2-[(3- nitrophenyl)methyloximinomethyl]phenyl}-3-methoxyacrylate, 3-chloro-7-(2-aza-2,7,7- trimethyl-oct-3-en-5-ine), 2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide, 3-iodo-2- propinyl alcohol, 4-chlorophenyl-3-iodopropargyl formal, 3-bromo-2,3-diiodo-2-propenyl ethylcarbamate, 2,3,3-triiodoallyl alcohol, 3-bromo-2,3-diiodo-2-propenyl alcohol, 3-iodo-2- propinyl n-butylcarbamate, 3-iodo-2-propinyl n-hexylcarbamate, 3-iodo-2-propinyl cyclohexyl- carbamate, 3-iodo-2-propinyl phenylcarbamate; phenol derivatives, such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5-dimethyl-4-chlorophenol, phenoxyethanol, dichlorophene, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2-benzyl-4-chlorophenol, 5-hydroxy-2(5H)-furanone; 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5- trimethylenedithiazolinone, 4,5-dichloro-(3H)-1 ,2-dithiol-3-one, 3,5-dimethyl-tetrahydro-1 ,3,5- thiadiazine-2-thione, N-(2-p-chlorobenzoylethyl)-hexaminium chloride, acibenzolar, acypetacs, alanycarb, albendazole, aldimorph, allicin, allyl alcohol, ametoctradin,
amisulbrom, amobam, ampropylfos, anilazine, asomate, aureofungin, azaconazole, azafendin, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiazole, benzalkonium chloride, benzamacril, benzamorf, benzohydroxamic acid, berberine, bethoxazin, biloxazol, binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S, boscalid, bromothalonil, bromuconazole, bupirimate, buthiobate, butylamine calcium polysulfide, captafol, captan, carbamorph, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chitosan, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chloroneb, chloropicrin, chlorothalonil, chlorozolinate, chlozolinate, climbazole, clotrimazole, clozylacon, copper containing compounds such as copper acetate, copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper oxyquinolate, copper silicate, copper sulphate, copper tallate, copper zinc chromate and Bordeaux mixture, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid,
cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole, cyproconazole, cyprodinil, dazomet, debacarb, decafentin, dehydroacetic acid, di-2-pyridyl disulphide 1 , 1 '- dioxide, dichlofluanid, diclomezine, dichlone, dicloran, dichlorophen, dichlozoline,
diclobutrazol, diclocymet, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O, O-di- iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetachlone, dimetconazole,
dimethomorph, dimethirimol, diniconazole, diniconazole-M, dinobuton, dinocap, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, dithioether, dodecyl dimethyl ammonium chloride, dodemorph, dodicin, dodine, doguadine, drazoxolon, edifenphos, enestroburin, epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin, ethilicin, ethyl (Z)-N-benzyl-N ([methyl (methyl- thioethylideneamino- oxycarbonyl) amino] thio)^-alaninate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, flupicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutanil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fuberidazole, furalaxyl, furametpyr, furcarbanil, furconazole, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, hexa chlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexylthiofos, hydrargaphen, hydroxyisoxazole, hymexazole, imazalil, imazalil sulphate, imibenconazole, iminoctadine, iminoctadine triacetate, inezin, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isopropanyl butyl carbamate, isoprothiolane, isopyrazam, isotianil, isovaledione, izopamfos, kasugamycin, kresoxim-methyl, LY186054, LY21 1795, LY248908, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mefenoxam, mepanipyrim, mepronil, mercuric chloride, mercurous chloride, meptyldinocap, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl bromide, methyl iodide, methyl isothiocyanate, metiram, metiram-zinc, metominostrobin, metrafenone, metsulfovax, milneb, moroxydine, myclobutanil, myclozolin, nabam, natamycin, neoasozin, nickel dimethyldithiocarbamate, nitrostyrene, nitrothal-iso- propyl, nuarimol, octhilinone, ofurace, organomercury compounds, orysastrobin, osthol, oxadixyl, oxasulfuron, oxine-copper, oxolinic acid, oxpoconazole, oxycarboxin, parinol, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, penthiopyrad, phenamacril, phenazin oxide, phosdiphen, phosetyl-AI, phosphorus acids, phthalide, picoxystrobin, piperalin,
polycarbamate, polyoxin D, polyoxrim, polyram, probenazole, prochloraz, procymidone, propamidine, propamocarb, propiconazole, propineb, propionic acid, proquinazid,
prothiocarb, prothioconazole, pyracarbolid, pyraclostrobin, pyrametrostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinacetol, quinazamid, quinconazole, quinomethionate, quinoxyfen, quintozene, rabenzazole,
santonin, sedaxane, silthiofam, simeconazole, sipconazole, sodium
pentachlorophenate, solatenol, spiroxamine, streptomycin, sulphur, sultropen, tebuconazole, tebfloquin, tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, 2- (thiocyanomethylthio) benzothiazole, thiophanate-methyl, thioquinox, thiram, tiadinil, timibenconazole, tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tricyclazole, tridemorph, ^ trifloxystrobin, triflumazole, triforine, triflumizole, triticonazole, uniconazole, urbacide, validamycin, valifenalate, vapam, vinclozolin, zarilamid, zineb, ziram, and zoxamide.
The compounds of the invention may also be used in combination with anthelmintic agents. Such anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP-444964 and EP-594291 . Additional anthelmintic agents include
semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO-9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel. Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
The compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE- 19520936.
The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO- 9615121 and also with anthelmintic active cyclic depsipeptides such as those described in WO-961 1945, WO-9319053, WO- 9325543, EP-626375, EP-382173, WO-9419334, EP- 382173, and EP-503538.
The compounds of the invention may be used in combination with other
ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron; ecdysone agonists such as tebufenozide and the like;
neonicotinoids such as imidacloprid and the like.
The compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers
W095/19363 or WO04/72086, particularly the compounds disclosed therein.
Other examples of such biologically active compounds that the compounds of the invention may be used in combination with include but are not restricted to the following:
Organophosphates: acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, methacriphos, methamidophos, methidathion, methyl- parathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate, phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate, phoxim, pirimiphos, 5 pirimiphos- methyl, profenofos, propaphos, proetamphos, prothiofos, pyraclofos,
pyridapenthion, quinalphos, sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos, thimeton, triazophos, trichlorfon, vamidothion.
Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb,
10 furathiocarb, HCN-801 , isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m- cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E) -
(1 R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate,
15 bifenthrin, beta -cyfluthrin, cyfluthrin, a-cypermethrin, beta -cypermethrin, bioallethrin,
bioallethrin((S)-cyclopentylisomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins
20 (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, t- fluvalinate, tefluthrin, tralomethrin, Zeta-cypermethrin.
Arthropod growth regulators: a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox,
25 etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide,
tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-1 18, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-
30 505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin,
dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI- 800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC-196,
35 neem guard, nidinorterfuran, nitenpyram, SD-35651 , WL-108477, pirydaryl, propargite,
protrifenbute, pymethrozine, pyridaben, pyrimidifen, NC-1 1 1 1 , R-195,RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601 , silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301 .
Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
Bactericides: chlortetracycline, oxytetracycline, streptomycin.
Other biological agents: enrofloxacin, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, carprofen,
metaflumizone, praziquarantel, triclabendazole.
Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal or insecticidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by insects or by phytopathogenic
microorganisms, preferably fungal organisms.
A further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a preferred individual compound as above-defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
Controlling or preventing means reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
A preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, e.g. a composition containing the compound of formula I, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active
compounds (surfactants).
Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as seed drenching agent, convenient dosages are from 10mg to 1 g of active substance per kg of seeds.
When the combinations of the present invention are used for treating seed, rates of 0.001 to 50 g of a compound of formula I per kg of seed, preferably from 0.01 to 10g per kg of seed are generally sufficient.
The compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Such compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects). Also conventional slow release formulations may be employed where long lasting efficacy is intended. Particularly formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g. the ondensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol. A seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula I together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like. Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.
The Examples which follow serve to illustrate the invention. Example 1 : This example illustrates the preparation of N-(1 ,1 -dimethyl-2-morpholino-2-oxo- ethyl)-2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carboxamide (Compound l.ad.464) a) Preparation of 2-isopropoxy-2-phenyl-ethanol
To a mixture of 2-phenyloxirane (7.00 g 58.3 mmol) and propan-2-ol (100 ml) was added, under nitrogen, iodine (1 .48 g, 5.83 mmol) at 20 °C. The reaction mixture was stirred for 2 hours at room temperature. The solvent was then removed under vacuum. The crude reaction mixture was taken up with ether (50 ml) and washed with an aqueous solution of Na2S203 until the yellow color of iodine disappeared. The organic layer was dried on magnesium sulphate and then filtered. The filtrate was evaporated under reduced pressure, and the residue was purified by flash chromatography (ethyl acetate/cyclohexane : 1/10) to obtain 2-isopropoxy-2-phenyl-ethanol. b) Preparation of 5-bromo-2-(2-isopropoxy-2-phenyl-ethoxy)pyridine-3-carboxylic acid
2-isopropoxy-2-phenyl-ethanol (1 .28 g, 7.12 mmol) was added to a room temperature suspension of sodium hydride (60% dispersion in mineral oil, 285 mg, 7.12 mmol) in dry tetrahydrofuran (30 ml) under nitrogen. The reaction mixture was stirred at room temperature for 30 minutes and 2,5-dibromopyridne-3-carboxylic acid (1 g, 3.56 mmol) was added. The reaction mixture was heated at reflux for 12 hours. After cooling to room temperature, the pH was adjusted to 3 by the addition of 3N aqueous HCI. The mixture was poured into brine ad extracted with ethyl acetate. The combined organics were dried and concentrated. The crude product was purified by flash chromatography using a gradient of cyclohexane and ethyl acetate to give 5-bromo-2-(2-isopropoxy-2-phenyl-ethoxy)pyridine-3-carboxylic acid. c) Preparation of tert-butyl 2-[[5-bromo-2-(2-isopropoxy-2-phenyl-ethoxy)pyridine-3- carbonyl]amino]-2-methyl-propanoate
Terf-butyl 2-amino-2-methylpropanoate hydrochloride (379 mg, 1 .84 mmol), 1 - [Bis(dimethylamino)methylene]-1 H-1 ,2,3-triazolo[4,5-b]pyridinium 3-oxid
hexafluorophosphate (884 mg, 2.21 mmol), N-ethyl-N-isopropyl-propan-2-amine (476 mg, 3.68 mmol), 5-bromo-2-(2-isopropoxy-2-phenyl-ethoxy)pyridine-3-carboxylic acid (700 mg, 1 .84 mmol) were mixed together in dimethylformamide (18 ml) and the reaction mixture was stirred at room temperature for 2 hours before it was quenched with an aqueous saturated solution of NaHC03 (30 ml). The aqueous phase was extracted with ethyl acetate (50 ml) and the organic phase was concentrated under reduced pressure. The residue was passed through a column of silica gel using cyclohexane and ethyl acetate (2/1 ) as eluent. This provide tert-butyl 2-[[5-bromo-2-(2-isopropoxy-2-phenyl-ethoxy)pyridine-3-carbonyl]amino]-2- methyl-propanoate. d) Preparation of tert-butyl 2-[[2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3- carbonyl]amino]-2-methyl-propanoate
A solution of tert-butyl 2-[[2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3- carbonyl]amino]-2-methyl-propanoate (830 mg, 1.59 mmol), lithium chloride (67.5 mg, 1.59 mmol), copper(l) iodide (31.9 mg, 0.159 mmol), tetrakis(triphenylphosphine)palladium(0) (194 mg, 0.159 mmol), and 2-(tributylstannyl)oxazole (1.16 g, 3.18 mmol) in 1 ,4 dioxane (20 ml) was stirred under nitrogen at 130 °C for 4 hours. The reaction was monitored by UPLC. Fresh tetrakis(triphenylphosphine)palladium(0) was then added and the reaction mixture was stir for a further 2 hours at 130 °C. The reaction mixture was then cooled down to ambient temperature, concentrated under reduced pressure, taken up with ethyl acetate (50 ml) and washed thorough twice with aqueous sodium hydroxide (1 N, 20 ml). The organic phase was concentrated under vacuum and absorbed onto isolute. A pad of 5 mm of KF powder was added on the loading cartridge. The sample was therefore purified by flash chromatography on silica gel with a gradient of ethyl acetate and cyclohexane to give tert-butyl 2-[[2-(2- isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carbonyl]amino]-2-methyl-propanoate. e) Preparation of 2-[[2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3- carbonyl]amino]-2-methyl-propanoic acid; 2,2,2-trifluoroacetic acid tert-butyl 2-[[2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3- carbonyl]amino]-2-methyl-propanoate (170 mg, 0.33 mmol) was diluted in dichloromethane (5 ml), trifluoroacetic acid (2 ml) was therefore added and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under vacuum and the crude material was used as such into the next step. f) Preparation of preparation of N-(1 ,1 -dimethyl-2-morpholino-2-oxo-ethyl)-2-(2-isopropoxy- 2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carboxamide (Compound I. ad.464)
2-[[2-(2-isopropoxy-2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carbonyl]amino]-2- methyl-propanoic acid; 2,2,2-trifluoroacetic acid (180 mg), 1 -[Bis(dimethylamino)methylene]- 1 H-1 ,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (68 mg, 0.17 mmol), N-ethyl- N-isopropyl-propan-2-amine (73 mg, 0.56 mmol), morpholine (18 mg, 0.21 mmol) were mixed together in dichloromethane (5 ml) and the reaction mixture was stirred at room temperature overnight before it was quenched with an aqueous saturated solution of
NaHC03 (5 ml). The chlorinated phase was isolated and concentrated under reduced pressure. The residue was passed through a column of silica gel using cyclohexane/ethyl acetate as eluent. This provided N-(1 ,1 -dimethyl-2-morpholino-2-oxo-ethyl)-2-(2-isopropoxy- 2-phenyl-ethoxy)-5-oxazol-2-yl-pyridine-3-carboxamide (Compound I. ad.464). Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
Table 1 below illustrates examples of individual compounds of formula I according to the invention.
Table 1 : individual compounds of formula I according to the invention
Comp. R R X1 X3 X4 L1-R3
No. 4-MOR = 4-morpholinyl
001 H 2-oxazoyl s 0 NH -CH2C(=0)NHCH3
002 CH3 2-oxazoyl s 0 NH -CH2C(=0)NHCH3
003 CH3 2-oxazoyl s 0 O -CH2C(=0)NHCH3
004 H 2-thiazolyl s 0 NH -CH2C(=0)NHCH3
005 CH3 2-thiazolyl s 0 NH -CH2C(=0)NHCH3
006 CH3 2-thiazolyl s 0 O -CH2C(=0)NHCH3
007 H 2-[1 ,3,4]oxadiazolyl s 0 NH -CH2C(=0)NHCH3
008 CH3 2-[1 ,3,4]oxadiazolyl s 0 NH -CH2C(=0)NHCH3
009 CH3 2-[1 ,3,4]oxadiazolyl s 0 O -CH2C(=0)NHCH3 H 5-isoxazolyl S 0 NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl S 0 NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl S 0 0 -CH2C(=0)NHCH3
H 2-oxazoyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 2-oxazoyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 2-oxazoyl CH=N 0 0 -CH2C(=0)NHCH3
H 2-thiazolyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 2-thiazolyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 2-thiazolyl CH=N 0 0 -CH2C(=0)NHCH3
H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 0 -CH2C(=0)NHCH3
H 5-isoxazolyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl CH=N 0 NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl CH=N 0 0 -CH2C(=0)NHCH3 cyclopropyl 5-isoxazolyl CH=N 0 0 -CH2C(=0)NHCH3
H 2-oxazoyl S NH NH -CH2C(=0)NHCH3
CH3 2-oxazoyl S NH NH -CH2C(=0)NHCH3
CH3 2-oxazoyl S NH 0 -CH2C(=0)NHCH3
H 2-thiazolyl S NH NH -CH2C(=0)NHCH3
CH3 2-thiazolyl S NH NH -CH2C(=0)NHCH3
CH3 2-thiazolyl S NH 0 -CH2C(=0)NHCH3
H 2-[1 ,3,4]oxadiazolyl S NH NH -CH2C(=0)NHCH3
CH3 2-[1 ,3,4]oxadiazolyl S NH NH -CH2C(=0)NHCH3
CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -CH2C(=0)NHCH3
H 5-isoxazolyl S NH NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl S NH NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl S NH 0 -CH2C(=0)NHCH3
H 2-oxazoyl CH=N NH NH -CH2C(=0)NHCH3
CH3 2-oxazoyl CH=N NH NH -CH2C(=0)NHCH3
CH3 2-oxazoyl CH=N NH 0 -CH2C(=0)NHCH3
H 2-thiazolyl CH=N NH NH -CH2C(=0)NHCH3
CH3 2-thiazolyl CH=N NH NH -CH2C(=0)NHCH3
CH3 2-thiazolyl CH=N NH 0 -CH2C(=0)NHCH3
H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH2C(=0)NHCH3
CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH2C(=0)NHCH3
CH3 2-[1 ,3,4]oxadiazolyl CH=N NH 0 -CH2C(=0)NHCH3 H 5-isoxazolyl CH=N NH NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl CH=N NH NH -CH2C(=0)NHCH3
CH3 5-isoxazolyl CH=N NH O -CH2C(=0)NHCH3 cyclopropyl 5-isoxazolyl CH=N NH O -CH2C(=0)NHCH3
H 2-oxazoyl S O NH -CH2C(=0)NHCH2CH3
CH3 2-oxazoyl S O NH -CH2C(=0)NHCH2CH3
CH3 2-oxazoyl S O O -CH2C(=0)NHCH2CH3
H 2-thiazolyl S O NH -CH2C(=0)NHCH2CH3
CH3 2-thiazolyl S O NH -CH2C(=0)NHCH2CH3
CH3 2-thiazolyl S O O -CH2C(=0)NHCH2CH3
H 2-[1 ,3,4]oxadiazolyl S O NH -CH2C(=0)NHCH2CH3
CH3 2-[1 ,3,4]oxadiazolyl S O NH -CH2C(=0)NHCH2CH3
CH3 2-[1 ,3,4]oxadiazolyl S O O -CH2C(=0)NHCH2CH3
H 5-isoxazolyl S O NH -CH2C(=0)NHCH2CH3
CH3 5-isoxazolyl S O NH -CH2C(=0)NHCH2CH3
CH3 5-isoxazolyl S O O -CH2C(=0)NHCH2CH3
H 2-oxazoyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 2-oxazoyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 2-oxazoyl CH=N O O -CH2C(=0)NHCH2CH3
H 2-thiazolyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 2-thiazolyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 2-thiazolyl CH=N O O -CH2C(=0)NHCH2CH3
H 2-[1 ,3,4]oxadiazolyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 2-[1 ,3,4]oxadiazolyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 2-[1 ,3,4]oxadiazolyl CH=N O O -CH2C(=0)NHCH2CH3
H 5-isoxazolyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 5-isoxazolyl CH=N O NH -CH2C(=0)NHCH2CH3
CH3 5-isoxazolyl CH=N O O -CH2C(=0)NHCH2CH3 cyclopropyl 5-isoxazolyl CH=N 0 O -CH2C(=0)NHCH2CH3
H 2-oxazoyl S NH NH -CH2C(=0)NHCH2CH3
CH3 2-oxazoyl S NH NH -CH2C(=0)NHCH2CH3
CH3 2-oxazoyl S NH O -CH2C(=0)NHCH2CH3
H 2-thiazolyl S NH NH -CH2C(=0)NHCH2CH3
CH3 2-thiazolyl S NH NH -CH2C(=0)NHCH2CH3
CH3 2-thiazolyl S NH O -CH2C(=0)NHCH2CH3
H 2-[1 ,3,4]oxadiazolyl S NH NH -CH2C(=0)NHCH2CH3
CH3 2-[1 ,3,4]oxadiazolyl S NH NH -CH2C(=0)NHCH2CH3 084 CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -CH2C(=0)NHCH2CH3
085 H 5-isoxazolyl S NH NH -CH2C(=0)NHCH2CH3
086 CH3 5-isoxazolyl S NH NH -CH2C(=0)NHCH2CH3
087 CH3 5-isoxazolyl S NH 0 -CH2C(=0)NHCH2CH3
088 H 2-oxazoyl CH=N NH NH -CH2C(=0)NHCH2CH3
089 CH3 2-oxazoyl CH=N NH NH -CH2C(=0)NHCH2CH3
090 CH3 2-oxazoyl CH=N NH 0 -CH2C(=0)NHCH2CH3
091 H 2-thiazolyl CH=N NH NH -CH2C(=0)NHCH2CH3
092 CH3 2-thiazolyl CH=N NH NH -CH2C(=0)NHCH2CH3
093 CH3 2-thiazolyl CH=N NH 0 -CH2C(=0)NHCH2CH3
094 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH2C(=0)NHCH2CH3
095 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH2C(=0)NHCH2CH3
096 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH 0 -CH2C(=0)NHCH2CH3
097 H 5-isoxazolyl CH=N NH NH -CH2C(=0)NHCH2CH3
098 CH3 5-isoxazolyl CH=N NH NH -CH2C(=0)NHCH2CH3
099 CH3 5-isoxazolyl CH=N NH 0 -CH2C(=0)NHCH2CH3
100 cyclopropyl 5-isoxazolyl CH=N NH 0 -CH2C(=0)NHCH2CH3
101 H 2-oxazoyl S 0 NH -CH(CH3)C(=0)NH2
102 CH3 2-oxazoyl S 0 NH -CH(CH3)C(=0)NH2
103 CH3 2-oxazoyl S 0 0 -CH(CH3)C(=0)NH2
104 H 2-thiazolyl S 0 NH -CH(CH3)C(=0)NH2
105 CH3 2-thiazolyl S 0 NH -CH(CH3)C(=0)NH2
106 CH3 2-thiazolyl S 0 0 -CH(CH3)C(=0)NH2
107 H 2-[1 ,3,4]oxadiazolyl S 0 NH -CH(CH3)C(=0)NH2
108 CH3 2-[1 ,3,4]oxadiazolyl S 0 NH -CH(CH3)C(=0)NH2
109 CH3 2-[1 ,3,4]oxadiazolyl S 0 0 -CH(CH3)C(=0)NH2
1 10 H 5-isoxazolyl S 0 NH -CH(CH3)C(=0)NH2
1 1 1 CH3 5-isoxazolyl S 0 NH -CH(CH3)C(=0)NH2
1 12 CH3 5-isoxazolyl S 0 0 -CH(CH3)C(=0)NH2
1 13 H 2-oxazoyl CH=N 0 NH -CH(CH3)C(=0)NH2
1 14 CH3 2-oxazoyl CH=N 0 NH -CH(CH3)C(=0)NH2
1 15 CH3 2-oxazoyl CH=N 0 0 -CH(CH3)C(=0)NH2
1 16 H 2-thiazolyl CH=N 0 NH -CH(CH3)C(=0)NH2
1 17 CH3 2-thiazolyl CH=N 0 NH -CH(CH3)C(=0)NH2
1 18 CH3 2-thiazolyl CH=N 0 0 -CH(CH3)C(=0)NH2
1 19 H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -CH(CH3)C(=0)NH2
120 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -CH(CH3)C(=0)NH2 121 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 O -CH(CH3)C(=0)NH2
122 H 5-isoxazolyl CH=N 0 NH -CH(CH3)C(=0)NH2
123 CH3 5-isoxazolyl CH=N 0 NH -CH(CH3)C(=0)NH2
124 CH3 5-isoxazolyl CH=N 0 O -CH(CH3)C(=0)NH2
125 cyclopropyl 5-isoxazolyl CH=N 0 O -CH(CH3)C(=0)NH2
126 H 2-oxazoyl S NH NH -CH(CH3)C(=0)NH2
127 CH3 2-oxazoyl S NH NH -CH(CH3)C(=0)NH2
128 CH3 2-oxazoyl S NH O -CH(CH3)C(=0)NH2
129 H 2-thiazolyl S NH NH -CH(CH3)C(=0)NH2
130 CH3 2-thiazolyl S NH NH -CH(CH3)C(=0)NH2
131 CH3 2-thiazolyl S NH O -CH(CH3)C(=0)NH2
132 H 2-[1 ,3,4]oxadiazolyl S NH NH -CH(CH3)C(=0)NH2
133 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -CH(CH3)C(=0)NH2
134 CH3 2-[1 ,3,4]oxadiazolyl S NH O -CH(CH3)C(=0)NH2
135 H 5-isoxazolyl S NH NH -CH(CH3)C(=0)NH2
136 CH3 5-isoxazolyl S NH NH -CH(CH3)C(=0)NH2
137 CH3 5-isoxazolyl S NH O -CH(CH3)C(=0)NH2
138 H 2-oxazoyl CH=N NH NH -CH(CH3)C(=0)NH2
139 CH3 2-oxazoyl CH=N NH NH -CH(CH3)C(=0)NH2
140 CH3 2-oxazoyl CH=N NH O -CH(CH3)C(=0)NH2
141 H 2-thiazolyl CH=N NH NH -CH(CH3)C(=0)NH2
142 CH3 2-thiazolyl CH=N NH NH -CH(CH3)C(=0)NH2
143 CH3 2-thiazolyl CH=N NH O -CH(CH3)C(=0)NH2
144 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH(CH3)C(=0)NH2
145 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH(CH3)C(=0)NH2
146 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH O -CH(CH3)C(=0)NH2
147 H 5-isoxazolyl CH=N NH NH -CH(CH3)C(=0)NH2
148 CH3 5-isoxazolyl CH=N NH NH -CH(CH3)C(=0)NH2
149 CH3 5-isoxazolyl CH=N NH O -CH(CH3)C(=0)NH2
150 cyclopropyl 5-isoxazolyl CH=N NH O -CH(CH3)C(=0)NH2
151 H 2-oxazoyl S O NH -CH(CH3)C(=0)NHCH3
152 CH3 2-oxazoyl S O NH -CH(CH3)C(=0)NHCH3
153 CH3 2-oxazoyl S O O -CH(CH3)C(=0)NHCH3
154 H 2-thiazolyl S O NH -CH(CH3)C(=0)NHCH3
155 CH3 2-thiazolyl S O NH -CH(CH3)C(=0)NHCH3
156 CH3 2-thiazolyl S O O -CH(CH3)C(=0)NHCH3
157 H 2-[1 ,3,4]oxadiazolyl S O NH -CH(CH3)C(=0)NHCH3 158 CH3 2-[1 ,3,4]oxadiazolyl S 0 NH -CH(CH3)C(=0)NHCH3
159 CH3 2-[1 ,3,4]oxadiazolyl S 0 0 -CH(CH3)C(=0)NHCH3
160 H 5-isoxazolyl S 0 NH -CH(CH3)C(=0)NHCH3
161 CH3 5-isoxazolyl S 0 NH -CH(CH3)C(=0)NHCH3
162 CH3 5-isoxazolyl S 0 0 -CH(CH3)C(=0)NHCH3
163 H 2-oxazoyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
164 CH3 2-oxazoyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
165 CH3 2-oxazoyl CH=N 0 0 -CH(CH3)C(=0)NHCH3
166 H 2-thiazolyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
167 CH3 2-thiazolyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
168 CH3 2-thiazolyl CH=N 0 0 -CH(CH3)C(=0)NHCH3
169 H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
170 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
171 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 0 -CH(CH3)C(=0)NHCH3
172 H 5-isoxazolyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
173 CH3 5-isoxazolyl CH=N 0 NH -CH(CH3)C(=0)NHCH3
174 CH3 5-isoxazolyl CH=N 0 0 -CH(CH3)C(=0)NHCH3
175 cyclopropyl 5-isoxazolyl CH=N 0 0 -CH(CH3)C(=0)NHCH3
176 H 2-oxazoyl S NH NH -CH(CH3)C(=0)NHCH3
177 CH3 2-oxazoyl S NH NH -CH(CH3)C(=0)NHCH3
178 CH3 2-oxazoyl S NH 0 -CH(CH3)C(=0)NHCH3
179 H 2-thiazolyl S NH NH -CH(CH3)C(=0)NHCH3
180 CH3 2-thiazolyl S NH NH -CH(CH3)C(=0)NHCH3
181 CH3 2-thiazolyl S NH 0 -CH(CH3)C(=0)NHCH3
182 H 2-[1 ,3,4]oxadiazolyl S NH NH -CH(CH3)C(=0)NHCH3
183 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -CH(CH3)C(=0)NHCH3
184 CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -CH(CH3)C(=0)NHCH3
185 H 5-isoxazolyl S NH NH -CH(CH3)C(=0)NHCH3
186 CH3 5-isoxazolyl S NH NH -CH(CH3)C(=0)NHCH3
187 CH3 5-isoxazolyl S NH 0 -CH(CH3)C(=0)NHCH3
188 H 2-oxazoyl CH=N NH NH -CH(CH3)C(=0)NHCH3
189 CH3 2-oxazoyl CH=N NH NH -CH(CH3)C(=0)NHCH3
190 CH3 2-oxazoyl CH=N NH 0 -CH(CH3)C(=0)NHCH3
191 H 2-thiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH3
192 CH3 2-thiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH3
193 CH3 2-thiazolyl CH=N NH 0 -CH(CH3)C(=0)NHCH3
194 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH3 195 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH3
196 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH O -CH(CH3)C(=0)NHCH3
197 H 5-isoxazolyl CH=N NH NH -CH(CH3)C(=0)NHCH3
198 CH3 5-isoxazolyl CH=N NH NH -CH(CH3)C(=0)NHCH3
199 CH3 5-isoxazolyl CH=N NH O -CH(CH3)C(=0)NHCH3
200 cyclopropyl 5-isoxazolyl CH=N NH O -CH(CH3)C(=0)NHCH3
201 H 2-oxazoyl S O NH -CH(CH3)C(=0)NHCH2CH3
202 CH3 2-oxazoyl S O NH -CH(CH3)C(=0)NHCH2CH3
203 CH3 2-oxazoyl S O O -CH(CH3)C(=0)NHCH2CH3
204 H 2-thiazolyl S O NH -CH(CH3)C(=0)NHCH2CH3
205 CH3 2-thiazolyl S O NH -CH(CH3)C(=0)NHCH2CH3
206 CH3 2-thiazolyl S O O -CH(CH3)C(=0)NHCH2CH3
207 H 2-[1 ,3,4]oxadiazolyl S O NH -CH(CH3)C(=0)NHCH2CH3
208 CH3 2-[1 ,3,4]oxadiazolyl S O NH -CH(CH3)C(=0)NHCH2CH3
209 CH3 2-[1 ,3,4]oxadiazolyl S O O -CH(CH3)C(=0)NHCH2CH3
210 H 5-isoxazolyl S O NH -CH(CH3)C(=0)NHCH2CH3
21 1 CH3 5-isoxazolyl S O NH -CH(CH3)C(=0)NHCH2CH3
212 CH3 5-isoxazolyl S O O -CH(CH3)C(=0)NHCH2CH3
213 H 2-oxazoyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
214 CH3 2-oxazoyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
215 CH3 2-oxazoyl CH=N O O -CH(CH3)C(=0)NHCH2CH3
216 H 2-thiazolyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
217 CH3 2-thiazolyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
218 CH3 2-thiazolyl CH=N O O -CH(CH3)C(=0)NHCH2CH3
219 H 2-[1 ,3,4]oxadiazolyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
220 CH3 2-[1 ,3,4]oxadiazolyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
221 CH3 2-[1 ,3,4]oxadiazolyl CH=N O O -CH(CH3)C(=0)NHCH2CH3
222 H 5-isoxazolyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
223 CH3 5-isoxazolyl CH=N O NH -CH(CH3)C(=0)NHCH2CH3
224 CH3 5-isoxazolyl CH=N O O -CH(CH3)C(=0)NHCH2CH3
225 cyclopropyl 5-isoxazolyl CH=N O O -CH(CH3)C(=0)NHCH2CH3
226 H 2-oxazoyl S NH NH -CH(CH3)C(=0)NHCH2CH3
227 CH3 2-oxazoyl S NH NH -CH(CH3)C(=0)NHCH2CH3
228 CH3 2-oxazoyl S NH O -CH(CH3)C(=0)NHCH2CH3
229 H 2-thiazolyl S NH NH -CH(CH3)C(=0)NHCH2CH3
230 CH3 2-thiazolyl S NH NH -CH(CH3)C(=0)NHCH2CH3
231 CH3 2-thiazolyl S NH O -CH(CH3)C(=0)NHCH2CH3 232 H 2-[1 ,3,4]oxadiazolyl S NH NH -CH(CH3)C(=0)NHCH2CH3
233 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -CH(CH3)C(=0)NHCH2CH3
234 CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -CH(CH3)C(=0)NHCH2CH3
235 H 5-isoxazolyl S NH NH -CH(CH3)C(=0)NHCH2CH3
236 CH3 5-isoxazolyl S NH NH -CH(CH3)C(=0)NHCH2CH3
237 CH3 5-isoxazolyl S NH 0 -CH(CH3)C(=0)NHCH2CH3
238 H 2-oxazoyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
239 CH3 2-oxazoyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
240 CH3 2-oxazoyl CH=N NH 0 -CH(CH3)C(=0)NHCH2CH3
241 H 2-thiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
242 CH3 2-thiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
243 CH3 2-thiazolyl CH=N NH 0 -CH(CH3)C(=0)NHCH2CH3
244 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
245 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
246 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH 0 -CH(CH3)C(=0)NHCH2CH3
247 H 5-isoxazolyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
248 CH3 5-isoxazolyl CH=N NH NH -CH(CH3)C(=0)NHCH2CH3
249 CH3 5-isoxazolyl CH=N NH 0 -CH(CH3)C(=0)NHCH2CH3
250 cyclopropyl 5-isoxazolyl CH=N NH 0 -CH(CH3)C(=0)NHCH2CH3
251 H 2-oxazoyl S 0 NH -C(CH3)2C02H
252 CH3 2-oxazoyl S 0 NH -C(CH3)2C02H
253 CH3 2-oxazoyl S 0 0 -C(CH3)2C02H
254 H 2-thiazolyl S 0 NH -C(CH3)2C02H
255 CH3 2-thiazolyl S 0 NH -C(CH3)2C02H
256 CH3 2-thiazolyl S 0 0 -C(CH3)2C02H
257 H 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C02H
258 CH3 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C02H
259 CH3 2-[1 ,3,4]oxadiazolyl S 0 0 -C(CH3)2C02H
260 H 5-isoxazolyl S 0 NH -C(CH3)2C02H
261 CH3 5-isoxazolyl S 0 NH -C(CH3)2C02H
262 CH3 5-isoxazolyl S 0 0 -C(CH3)2C02H
263 H 2-oxazoyl CH=N 0 NH -C(CH3)2C02H
264 CH3 2-oxazoyl CH=N 0 NH -C(CH3)2C02H
265 CH3 2-oxazoyl CH=N 0 0 -C(CH3)2C02H
266 H 2-thiazolyl CH=N 0 NH -C(CH3)2C02H
267 CH3 2-thiazolyl CH=N 0 NH -C(CH3)2C02H
268 CH3 2-thiazolyl CH=N 0 0 -C(CH3)2C02H 269 H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C02H
270 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C02H
271 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 O -C(CH3)2C02H
272 H 5-isoxazolyl CH=N 0 NH -C(CH3)2C02H
273 CH3 5-isoxazolyl CH=N 0 NH -C(CH3)2C02H
274 CH3 5-isoxazolyl CH=N 0 O -C(CH3)2C02H
275 cyclopropyl 5-isoxazolyl CH=N 0 O -C(CH3)2C02H
276 H 2-oxazoyl S NH NH -C(CH3)2C02H
277 CH3 2-oxazoyl S NH NH -C(CH3)2C02H
278 CH3 2-oxazoyl S NH O -C(CH3)2C02H
279 H 2-thiazolyl S NH NH -C(CH3)2C02H
280 CH3 2-thiazolyl S NH NH -C(CH3)2C02H
281 CH3 2-thiazolyl S NH O -C(CH3)2C02H
282 H 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C02H
283 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C02H
284 CH3 2-[1 ,3,4]oxadiazolyl S NH O -C(CH3)2C02H
285 H 5-isoxazolyl S NH NH -C(CH3)2C02H
286 CH3 5-isoxazolyl S NH NH -C(CH3)2C02H
287 CH3 5-isoxazolyl S NH O -C(CH3)2C02H
288 H 2-oxazoyl CH=N NH NH -C(CH3)2C02H
289 CH3 2-oxazoyl CH=N NH NH -C(CH3)2C02H
290 CH3 2-oxazoyl CH=N NH O -C(CH3)2C02H
291 H 2-thiazolyl CH=N NH NH -C(CH3)2C02H
292 CH3 2-thiazolyl CH=N NH NH -C(CH3)2C02H
293 CH3 2-thiazolyl CH=N NH O -C(CH3)2C02H
294 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C02H
295 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C02H
296 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH O -C(CH3)2C02H
297 H 5-isoxazolyl CH=N NH NH -C(CH3)2C02H
298 CH3 5-isoxazolyl CH=N NH NH -C(CH3)2C02H
299 CH3 5-isoxazolyl CH=N NH O -C(CH3)2C02H
300 cyclopropyl 5-isoxazolyl CH=N NH O -C(CH3)2C02H
301 H 2-oxazoyl S O NH -C(CH3)2C(=0)NH2
302 CH3 2-oxazoyl S O NH -C(CH3)2C(=0)NH2
303 CH3 2-oxazoyl S O O -C(CH3)2C(=0)NH2
304 H 2-thiazolyl S O NH -C(CH3)2C(=0)NH2
305 CH3 2-thiazolyl S O NH -C(CH3)2C(=0)NH2 306 CH3 2-thiazolyl S 0 0 -C(CH3)2C(=0)NH2
307 H 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C(=0)NH2
308 CH3 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C(=0)NH2
309 CH3 2-[1 ,3,4]oxadiazolyl S 0 0 -C(CH3)2C(=0)NH2
310 H 5-isoxazolyl S 0 NH -C(CH3)2C(=0)NH2
31 1 CH3 5-isoxazolyl S 0 NH -C(CH3)2C(=0)NH2
312 CH3 5-isoxazolyl S 0 0 -C(CH3)2C(=0)NH2
313 H 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)NH2
314 CH3 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)NH2
315 CH3 2-oxazoyl CH=N 0 0 -C(CH3)2C(=0)NH2
316 H 2-thiazolyl CH=N 0 NH -C(CH3)2C(=0)NH2
317 CH3 2-thiazolyl CH=N 0 NH -C(CH3)2C(=0)NH2
318 CH3 2-thiazolyl CH=N 0 0 -C(CH3)2C(=0)NH2
319 H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C(=0)NH2
320 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C(=0)NH2
321 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 0 -C(CH3)2C(=0)NH2
322 H 5-isoxazolyl CH=N 0 NH -C(CH3)2C(=0)NH2
323 CH3 5-isoxazolyl CH=N 0 NH -C(CH3)2C(=0)NH2
324 CH3 5-isoxazolyl CH=N 0 0 -C(CH3)2C(=0)NH2
325 cyclopropyl 5-isoxazolyl CH=N 0 0 -C(CH3)2C(=0)NH2
326 H 2-oxazoyl S NH NH -C(CH3)2C(=0)NH2
327 CH3 2-oxazoyl S NH NH -C(CH3)2C(=0)NH2
328 CH3 2-oxazoyl S NH 0 -C(CH3)2C(=0)NH2
329 H 2-thiazolyl S NH NH -C(CH3)2C(=0)NH2
330 CH3 2-thiazolyl S NH NH -C(CH3)2C(=0)NH2
331 CH3 2-thiazolyl S NH 0 -C(CH3)2C(=0)NH2
332 H 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)NH2
333 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)NH2
334 CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -C(CH3)2C(=0)NH2
335 H 5-isoxazolyl S NH NH -C(CH3)2C(=0)NH2
336 CH3 5-isoxazolyl S NH NH -C(CH3)2C(=0)NH2
337 CH3 5-isoxazolyl S NH 0 -C(CH3)2C(=0)NH2
338 H 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)NH2
339 CH3 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)NH2
340 CH3 2-oxazoyl CH=N NH 0 -C(CH3)2C(=0)NH2
341 H 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)NH2
342 CH3 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)NH2 343 CH3 2-thiazolyl CH=N NH O -C(CH3)2C(=0)NH2
344 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)NH2
345 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)NH2
346 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH O -C(CH3)2C(=0)NH2
347 H 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)NH2
348 CH3 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)NH2
349 CH3 5-isoxazolyl CH=N NH O -C(CH3)2C(=0)NH2
350 cyclopropyl 5-isoxazolyl CH=N NH O -C(CH3)2C(=0)NH2
351 H 2-oxazoyl S O NH -C(CH3)2C(=0)NHCH3
352 CH3 2-oxazoyl S O NH -C(CH3)2C(=0)NHCH3
353 CH3 2-oxazoyl S O O -C(CH3)2C(=0)NHCH3
354 H 2-thiazolyl S O NH -C(CH3)2C(=0)NHCH3
355 CH3 2-thiazolyl S O NH -C(CH3)2C(=0)NHCH3
356 CH3 2-thiazolyl S O O -C(CH3)2C(=0)NHCH3
357 H 2-[1 ,3,4]oxadiazolyl S O NH -C(CH3)2C(=0)NHCH3
358 CH3 2-[1 ,3,4]oxadiazolyl S O NH -C(CH3)2C(=0)NHCH3
359 CH3 2-[1 ,3,4]oxadiazolyl S O O -C(CH3)2C(=0)NHCH3
360 H 5-isoxazolyl S O NH -C(CH3)2C(=0)NHCH3
361 CH3 5-isoxazolyl S O NH -C(CH3)2C(=0)NHCH3
362 CH3 5-isoxazolyl S O O -C(CH3)2C(=0)NHCH3
363 H 2-oxazoyl CH=N O NH -C(CH3)2C(=0)NHCH3
364 CH3 2-oxazoyl CH=N O NH -C(CH3)2C(=0)NHCH3
365 CH3 2-oxazoyl CH=N O O -C(CH3)2C(=0)NHCH3
366 H 2-thiazolyl CH=N O NH -C(CH3)2C(=0)NHCH3
367 CH3 2-thiazolyl CH=N O NH -C(CH3)2C(=0)NHCH3
368 CH3 2-thiazolyl CH=N O O -C(CH3)2C(=0)NHCH3
369 H 2-[1 ,3,4]oxadiazolyl CH=N O NH -C(CH3)2C(=0)NHCH3
370 CH3 2-[1 ,3,4]oxadiazolyl CH=N O NH -C(CH3)2C(=0)NHCH3
371 CH3 2-[1 ,3,4]oxadiazolyl CH=N O O -C(CH3)2C(=0)NHCH3
372 H 5-isoxazolyl CH=N O NH -C(CH3)2C(=0)NHCH3
373 CH3 5-isoxazolyl CH=N O NH -C(CH3)2C(=0)NHCH3
374 CH3 5-isoxazolyl CH=N O O -C(CH3)2C(=0)NHCH3
375 cyclopropyl 5-isoxazolyl CH=N O O -C(CH3)2C(=0)NHCH3
376 H 2-oxazoyl S NH NH -C(CH3)2C(=0)NHCH3
377 CH3 2-oxazoyl S NH NH -C(CH3)2C(=0)NHCH3
378 CH3 2-oxazoyl S NH O -C(CH3)2C(=0)NHCH3
379 H 2-thiazolyl S NH NH -C(CH3)2C(=0)NHCH3 380 CH3 2-thiazolyl S NH NH -C(CH3)2C(=0)NHCH3
381 CH3 2-thiazolyl S NH 0 -C(CH3)2C(=0)NHCH3
382 H 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)NHCH3
383 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)NHCH3
384 CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -C(CH3)2C(=0)NHCH3
385 H 5-isoxazolyl S NH NH -C(CH3)2C(=0)NHCH3
386 CH3 5-isoxazolyl S NH NH -C(CH3)2C(=0)NHCH3
387 CH3 5-isoxazolyl S NH 0 -C(CH3)2C(=0)NHCH3
388 H 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)NHCH3
389 CH3 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)NHCH3
390 CH3 2-oxazoyl CH=N NH 0 -C(CH3)2C(=0)NHCH3
391 H 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH3
392 CH3 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH3
393 CH3 2-thiazolyl CH=N NH 0 -C(CH3)2C(=0)NHCH3
394 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH3
395 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH3
396 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH 0 -C(CH3)2C(=0)NHCH3
397 H 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)NHCH3
398 CH3 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)NHCH3
399 CH3 5-isoxazolyl CH=N NH 0 -C(CH3)2C(=0)NHCH3
400 cyclopropyl 5-isoxazolyl CH=N NH 0 -C(CH3)2C(=0)NHCH3
401 H 2-oxazoyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
402 CH3 2-oxazoyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
403 CH3 2-oxazoyl S 0 0 -C(CH3)2C(=0)NHCH2CH3
404 H 2-thiazolyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
405 CH3 2-thiazolyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
406 CH3 2-thiazolyl S 0 0 -C(CH3)2C(=0)NHCH2CH3
407 H 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
408 CH3 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
409 CH3 2-[1 ,3,4]oxadiazolyl S 0 0 -C(CH3)2C(=0)NHCH2CH3
410 H 5-isoxazolyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
41 1 CH3 5-isoxazolyl S 0 NH -C(CH3)2C(=0)NHCH2CH3
412 CH3 5-isoxazolyl S 0 0 -C(CH3)2C(=0)NHCH2CH3
413 H 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
414 CH3 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
415 CH3 2-oxazoyl CH=N 0 0 -C(CH3)2C(=0)NHCH2CH3
416 H 2-thiazolyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3 417 CH3 2-thiazolyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
418 CH3 2-thiazolyl CH=N 0 O -C(CH3)2C(=0)NHCH2CH3
419 H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
420 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
421 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 O -C(CH3)2C(=0)NHCH2CH3
422 H 5-isoxazolyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
423 CH3 5-isoxazolyl CH=N 0 NH -C(CH3)2C(=0)NHCH2CH3
424 CH3 5-isoxazolyl CH=N 0 O -C(CH3)2C(=0)NHCH2CH3
425 cyclopropyl 5-isoxazolyl CH=N 0 O -C(CH3)2C(=0)NHCH2CH3
426 H 2-oxazoyl S NH NH -C(CH3)2C(=0)NHCH2CH3
427 CH3 2-oxazoyl S NH NH -C(CH3)2C(=0)NHCH2CH3
428 CH3 2-oxazoyl S NH O -C(CH3)2C(=0)NHCH2CH3
429 H 2-thiazolyl S NH NH -C(CH3)2C(=0)NHCH2CH3
430 CH3 2-thiazolyl S NH NH -C(CH3)2C(=0)NHCH2CH3
431 CH3 2-thiazolyl S NH O -C(CH3)2C(=0)NHCH2CH3
432 H 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)NHCH2CH3
433 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)NHCH2CH3
434 CH3 2-[1 ,3,4]oxadiazolyl S NH O -C(CH3)2C(=0)NHCH2CH3
435 H 5-isoxazolyl S NH NH -C(CH3)2C(=0)NHCH2CH3
436 CH3 5-isoxazolyl S NH NH -C(CH3)2C(=0)NHCH2CH3
437 CH3 5-isoxazolyl S NH O -C(CH3)2C(=0)NHCH2CH3
438 H 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
439 CH3 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
440 CH3 2-oxazoyl CH=N NH O -C(CH3)2C(=0)NHCH2CH3
441 H 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
442 CH3 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
443 CH3 2-thiazolyl CH=N NH O -C(CH3)2C(=0)NHCH2CH3
444 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
445 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
446 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH O -C(CH3)2C(=0)NHCH2CH3
447 H 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
448 CH3 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)NHCH2CH3
449 CH3 5-isoxazolyl CH=N NH O -C(CH3)2C(=0)NHCH2CH3
450 cyclopropyl 5-isoxazolyl CH=N NH O -C(CH3)2C(=0)NHCH2CH3
451 H 2-oxazoyl S O NH -C(CH3)2C(=0)-4-MOR
452 CH3 2-oxazoyl S O NH -C(CH3)2C(=0)-4-MOR
453 CH3 2-oxazoyl S O O -C(CH3)2C(=0)-4-MOR 454 H 2-thiazolyl S 0 NH -C(CH3)2C(=0)-4-MOR
455 CH3 2-thiazolyl S 0 NH -C(CH3)2C(=0)-4-MOR
456 CH3 2-thiazolyl S 0 0 -C(CH3)2C(=0)-4-MOR
457 H 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C(=0)-4-MOR
458 CH3 2-[1 ,3,4]oxadiazolyl S 0 NH -C(CH3)2C(=0)-4-MOR
459 CH3 2-[1 ,3,4]oxadiazolyl S 0 0 -C(CH3)2C(=0)-4-MOR
460 H 5-isoxazolyl S 0 NH -C(CH3)2C(=0)-4-MOR
461 CH3 5-isoxazolyl S 0 NH -C(CH3)2C(=0)-4-MOR
462 CH3 5-isoxazolyl S 0 0 -C(CH3)2C(=0)-4-MOR
463 H 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
464 CH3 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
465 CH3 2-oxazoyl CH=N 0 0 -C(CH3)2C(=0)-4-MOR
466 H 2-thiazolyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
467 CH3 2-thiazolyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
468 CH3 2-thiazolyl CH=N 0 0 -C(CH3)2C(=0)-4-MOR
469 H 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
470 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
471 CH3 2-[1 ,3,4]oxadiazolyl CH=N 0 0 -C(CH3)2C(=0)-4-MOR
472 H 5-isoxazolyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
473 CH3 5-isoxazolyl CH=N 0 NH -C(CH3)2C(=0)-4-MOR
474 CH3 5-isoxazolyl CH=N 0 0 -C(CH3)2C(=0)-4-MOR
475 cyclopropyl 5-isoxazolyl CH=N 0 0 -C(CH3)2C(=0)-4-MOR
476 H 2-oxazoyl S NH NH -C(CH3)2C(=0)-4-MOR
477 CH3 2-oxazoyl S NH NH -C(CH3)2C(=0)-4-MOR
478 CH3 2-oxazoyl S NH 0 -C(CH3)2C(=0)-4-MOR
479 H 2-thiazolyl S NH NH -C(CH3)2C(=0)-4-MOR
480 CH3 2-thiazolyl S NH NH -C(CH3)2C(=0)-4-MOR
481 CH3 2-thiazolyl S NH 0 -C(CH3)2C(=0)-4-MOR
482 H 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)-4-MOR
483 CH3 2-[1 ,3,4]oxadiazolyl S NH NH -C(CH3)2C(=0)-4-MOR
484 CH3 2-[1 ,3,4]oxadiazolyl S NH 0 -C(CH3)2C(=0)-4-MOR
485 H 5-isoxazolyl S NH NH -C(CH3)2C(=0)-4-MOR
486 CH3 5-isoxazolyl S NH NH -C(CH3)2C(=0)-4-MOR
487 CH3 5-isoxazolyl S NH 0 -C(CH3)2C(=0)-4-MOR
488 H 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
489 CH3 2-oxazoyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
490 CH3 2-oxazoyl CH=N NH 0 -C(CH3)2C(=0)-4-MOR 491 H 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
492 CH3 2-thiazolyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
493 CH3 2-thiazolyl CH=N NH 0 -C(CH3)2C(=0)-4-MOR
494 H 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
495 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
496 CH3 2-[1 ,3,4]oxadiazolyl CH=N NH 0 -C(CH3)2C(=0)-4-MOR
497 H 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
498 CH3 5-isoxazolyl CH=N NH NH -C(CH3)2C(=0)-4-MOR
499 CH3 5-isoxazolyl CH=N NH 0 -C(CH3)2C(=0)-4-MOR
500 cyclopropyl 5-isoxazolyl CH=N NH 0 -C(CH3)2C(=0)-4-MOR
501 CH3 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)N(CH3)2
502 CH3 2-oxazoyl CH=N 0 NH
C(CH3)2C(=0)NHCH2C≡CH
503 CH3 2-oxazoyl CH=N 0 NH -C(CH3)2C(=0)NHCH2-(2- furyl) where
a) 503 compounds of formula (I. a):
Figure imgf000048_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . b) 503 compounds of formula (l.b):
Figure imgf000048_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . c) 503 compounds of formula (l.c):
Figure imgf000049_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . d) 503 compounds of formula (l.d):
Figure imgf000049_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . e) 503 compounds of formula (l.e):
Figure imgf000049_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . f) 503 compounds of formula (l.f):
Figure imgf000049_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . g) 503 compounds of formula (l.g):
Figure imgf000050_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . h) 503 compounds of formula (l.h):
Figure imgf000050_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . i) 503 compounds of formula (l.i):
Figure imgf000050_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . j) 503 compounds of formula (l.j):
Figure imgf000050_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . k) 503 compounds of formula (l.k):
Figure imgf000051_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . m) 503 compounds of formula (l.m):
Figure imgf000051_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . n) 503 compounds of formula (l.n):
Figure imgf000051_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . o) 503 compounds of formula (l.o):
Figure imgf000051_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . p) 503 compounds of formula (l.p):
Figure imgf000052_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . q) 503 compounds of formula (l.q):
Figure imgf000052_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . r) 503 compounds of formula (l.r):
Figure imgf000052_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . s) 503 compounds of formula (l.s):
Figure imgf000052_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . t) 503 compounds of formula (l.t):
Figure imgf000053_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . u) 503 compounds of formula (l.u):
Figure imgf000053_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . v) 503 compounds of formula (l.v):
Figure imgf000053_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . w) 503 compounds of formula (l.w):
Figure imgf000053_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . x) 503 compounds of formula (l.x):
Figure imgf000054_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1. y) 503 compounds of formula l.y):
Figure imgf000054_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . z) 503 compounds of formula l.z):
Figure imgf000054_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . aa) 503 compounds of formula l.aa):
Figure imgf000054_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ab) 503 compounds of formula (l.ab):
Figure imgf000055_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ac) 503 compounds of formula l.ac):
Figure imgf000055_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ad) 503 compounds of formula I. ad):
Figure imgf000055_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ae) 503 compounds of formula l.ae):
Figure imgf000055_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . f) 503 compounds of formula (l.af):
Figure imgf000056_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ag) 503 compounds of formula (l.ag):
Figure imgf000056_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ah) 503 compounds of formula (I. ah):
Figure imgf000056_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ai) 503 compounds of formula (l.ai):
Figure imgf000056_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . j) 503 compounds of formula (l.aj):
Figure imgf000057_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ak) 503 compounds of formula (lak):
Figure imgf000057_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . am) 503 compounds of formula (I. am):
Figure imgf000057_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . an) 503 compounds of formula (I. an):
Figure imgf000057_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . o) 503 compounds of formula (l.ao):
Figure imgf000058_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ap) 503 compounds of formula (l.ap):
Figure imgf000058_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . aq) 503 compounds of formula (l.aq):
Figure imgf000058_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ar) 503 compounds of formula (l.ar):
Figure imgf000058_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . as) 503 compounds of formula (I. as):
Figure imgf000059_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . at) 503 compounds of formula (I. at):
Figure imgf000059_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . au) 503 compounds of formula (l.au):
Figure imgf000059_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . av) 503 compounds of formula (l.av):
Figure imgf000059_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . w) 503 compounds of formula (Law):
Figure imgf000060_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ax) 503 compounds of formula (Lax):
Figure imgf000060_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . ay) 503 compounds of formula (Lay):
Figure imgf000060_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . az) 503 compounds of formula (l.az):
Figure imgf000060_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . a) 503 compounds of formula (l.ba):
Figure imgf000061_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . bb) 503 compounds of formula (l.bb):
Figure imgf000061_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . be) 503 compounds of formula (I. be):
Figure imgf000061_0003
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . bd) 503 compounds of formula (l.bd):
Figure imgf000061_0004
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 e) 503 compounds of formula (I. be):
Figure imgf000062_0001
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 . bf) 503 compounds of formula (l.bf):
Figure imgf000062_0002
wherein R1, R2, R3, X1, X3, X4 and L1 are as defined in Table 1 .
The Examples which follow serve to illustrate the invention, "active ingredient" denoting a mixture of compound I and compounds of component (B+C) in a specific mixing ratio.
Throughout this description, temperatures are given in degrees Celsius and "m.p." means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the method is: (ACQUITY UPLC from Waters, Phenomenex Gemini C18, 3 μηη particle size, 1 10 Angstrom, 30 x 3 mm column, 1 .7mL/min., 60 °C, H20 + 0.05% HCOOH (95%) / CH3CN/MeOH 4:1 + 0.04% HCOOH (5%) - 2 min. - CH3CN/MeOH 4:1 + 0.04% HCOOH (5%) - 0.8 min., ACQUITY SQD Mass Spectrometer from Waters, ionization method: electrospray (ESI), Polarity: positive ions, Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700)).
Table 2: Melting point and LC/MS data for compounds of Table 1
Compound No. Melting point (°C) LC/MS
I.ad.314 Rt = 0.94 min; MS: m/z = 467 (M+1 ) l.ad.364 Rt = 1 .00 min; MS: m/z = 467 (M+1 ) Compound No. Melting point (°C) LC/MS
I.ad.414 Rt = 1 .04 min; MS: m/z = 495 (M+1 ) l.ad.464 Rt = 1 .02 min; MS: m/z = 523 (M+1 ) l.ad.501 Rt = 1 .00 min; MS: m/z = 495 (M+1 ) l.ad.502 Rt = 1 .01 min; MS: m/z = 505 (M+1 ) l.ad.503 Rt = 1 .08 min; MS: m/z = 547 (M+1 )
Formulation Examples
Wettable powders a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % sodium lignosulfonate 5 % 5 %
sodium lauryl sulfate 3 % - 5 % sodium diisobutylnaphthalenesulfonate - 6 % 10 % phenol polyethylene glycol ether - 2 %
(7-8 mol of ethylene oxide)
highly dispersed silicic acid 5 % 10 % 10 %
Kaolin 62 % 27 %
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
Powders for drv seed treatment a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % -
Kaolin 65 % 40 % -
Talcum - 20
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
Emulsifiable concentrate
active ingredient [compound of formula (I)] 10 %
octylphenol polyethylene glycol ether 3 %
(4-5 mol of ethylene oxide)
calcium dodecylbenzenesulfonate 3 %
castor oil polyglycol ether (35 mol of ethylene oxide) 4 % Cyclohexanone 30 %
xylene mixture 50 %
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Dusts a) b) c)
Active ingredient [compound of formula (I)] 5 % 6 % 4 % talcum 95 %
Kaolin 94 %
mineral filler 96 %
Ready-for-use dusts are obtained by mixing active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders also be used for dry dressings for seed.
Extruder granules
Active ingredient [compound of formula (I)] 15 %
sodium lignosulfonate 2 %
carboxymethylcellulose 1 %
Kaolin 82 %
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
Coated granules
Active ingredient [compound of formula (I)] 8 %
polyethylene glycol (mol. wt. 200) 3 %
Kaolin 89 %
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
Suspension concentrate
active ingredient [compound of formula (I)] 40 %
propylene glycol 10 %
nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
Sodium lignosulfonate 10 %
carboxymethylcellulose 1 %
silicone oil (in the form of a 75 % emulsion in water) 1 %
Water 32 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Flowable concentrate for seed treatment
active ingredient [compound of formula (I)] 40 %
propylene glycol 5 %
copolymer butanol PO/EO 2 %
tristyrenephenole with 10-20 moles EO 2 %
1 ,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 %
monoazo-pigment calcium salt 5 %
Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
Water 45.3 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Slow Release Capsule Suspension
28 parts of a combination of the compound of formula I are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1 ). This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1 ,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose. Biological examples
Alternaria solani I tomato / leaf disc (early blight)
Tomato leaf disks cv. Baby are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf disks are incubated at 23 °C / 21 °C (day/night) and 80% rh under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check disk leaf disks (5 - 7 days after application).
Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici) I wheat / leaf disc preventative (Powdery mildew on wheat)
Wheat leaf segments cv. Kanzler are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated by shaking powdery mildew infected plants above the test plates 1 day after application. The inoculated leaf disks are incubated at 20°C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate chamber and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check leaf segments (6 - 8 days after application).
Magnaporthe grisea (Pyricularia oryzae) I rice / leaf disc preventative (Rice Blast)
Rice leaf segments cv. Ballila are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segments are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments are incubated at 22°C and 80% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5 - 7 days after application). Monographella nivalis (Microdochium nivale) / liquid culture (foot rot cereals)
Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 4-5 days after application.
Mvcosphaerella arachidis (Cercospora arachidicola) I liquid culture (early leaf spot)
Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 4-5 days after application. Mycosphaerella graminicola (Septoria tritici) I liquid culture (Septoria blotch) Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 4-5 days after application.
Phaeosphaeria nodorum (Septoria nodorum) /wheat / leaf disc preventative (Glume blotch) Wheat leaf segments cv. Kanzler are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 2 days after application. The inoculated test leaf disks are incubated at 20°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
Phytophthora infestans I tomato / leaf disc preventative (tomato late blight)
Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
Compounds I. ad.501 and I. ad.503 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.
Plasmopara viticola I grape / leaf disc preventative (grape downy mildew)
Grape vine leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).
Puccinia recondita f. sp. tritici I wheat / leaf disc preventative (Brown rust) ^
Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments are incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application).
Pyrenophora teres I barley / leaf disc preventative (Net blotch)
Barley leaf segments cv. Hasso are placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segmens are inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments are incubated at 20°C and 65% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5 - 7 days after application).

Claims

What is claimed is:
1 . A compound of formula I:
Figure imgf000069_0001
Wherein:
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl, C2-C6alkynyl or C3-C6cycloalkyl in which the alkyl, alkynyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is heterocyclyl, which can be optionally substituted by one or more R6;
R3 is -C(=0)R6, -S(=0)R6, -S(=0)2R6 or heterocyclyl, which can be optionally substituted by one or more R6;
R4 is C2-C6alkynyl, C3-C6cycloalkyl, aryl or heterocyclyl, in which the alkynyl, cycloalkyi, aryl and heterocyclyl groups are optionally substituted by one or more R6;
R5 is hydrogen, CrC6alkyl, CrC6alkoxy, C2-C6alkenyl, C2-C6alkenyloxy, C2-C6alkynyl, C2- C6alkynyloxy, C3-C6cycloalkyl, C3-C6cycloalkyloxy or aryl, in which the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyi and aryl groups are optionally substituted by one or more R6;
R6 is hydrogen, halogen, cyano, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6alkenylthio, C2-C6haloalkenyloxy, C2-C6haloalkenylthio, C2-C6alkynyl, C2- C6alkynyloxy, C2-C6alkynylthio, C3-C6cycloalkyl, C3-C6halocycloalkyl, C3-C6cycloalkyloxy, C3- Cecycloalkylthio, C3-C6halocycloalkyloxy, C3-C6halocycloalkylthio, -NH(CrC6alkyl), -N(C C6alkyl)2, -NH(C C6haloalkyl), -N(C C6haloalkyl)2, -NH(C2-C6alkenyl), -N(C2-C6alkenyl)2, - NH(C2-C6haloalkenyl), -N(C2-C6haloalkenyl)2, -NH(C2-C6alkynyl), -N(C2-C6alkynyl)2, -NH(C3- Cecycloalkyl), -N(C3-C6cycloalkyl)2, -NH(C3-C6halocycloalkyl), -N(C3-C6halocycloalkyl)2, - NHC(=0)(CrC6alkyl), -N(C(=0)(C C6alkyl))2, -NHC(=0)(C C6haloalkyl), N(C(=0)(C C6haloalkyl))2, -NHC(=0)(C C6alkoxy), -N(C(=0)(C C6alkoxy))2, -NHC(=0)(C
Cehaloalkoxy), -N(C(=0)(C C6haloalkoxy))2, -NHC(=0)(C2-C6alkenyl), -N(C(=0)(C2- C6alkenyl))2, -NHC(=0)(C2-C6haloalkenyl), -N(C(=0)(C2-C6haloalkenyl))2, -NHC(=0)(C2- C6alkenyloxy), -N(C(=0)(C2-C6alkenyloxy))2, -NHC(=0)(C2-C6haloalkenyloxy), -N(C(=0)(C2- C6haloalkenyloxy))2, -NHC(=0)(C2-C6alkynyl), -N(C(=0)(C2-C6alkynyl))2, -NHC(=0)(C2- C6alkynyloxy), -N(C(=0)(C2-C6alkynyloxy))2! -NHC(=0)(C3-C6cycloalkyl), -N(C(=0)(C3- C6cycloalkyl))2, -NHC(=0)(C3-C6halocycloalkyl), -N(C(=0)(C3-C6halocycloalkyl))2! - NHC(=0)(C3-C6cycloalkyloxy), -N(C(=0)(C3-C6cycloalkyloxy))2! -NHC(=0)(C3- Cehalocycloalkyloxy), -N(C(=0)(C3-C6halocycloalkyloxy))2, -OC(=0)(CrC6alkyl), -OC(=0)(C CehaloalkyI), -OC(=0)(Ci-C6alkoxy), -OC(=0)(Ci-C6haloalkoxy), -OC(=0)(C2-C6alkenyl), - OC(=0)(C2-C6haloalkenyl), -OC(=0)(C2-C6alkenyloxy), -OC(=0)(C2-C6haloalkenyloxy), - OC(=0)(C2-C6alkynyl), -OC(=0)(C2-C6alkynyloxy), -OC(=0)(C3-C6cycloalkyl), -OC(=0)(C3- Cehalocycloalkyl), -OC(=0)(C3-C6cycloalkyloxy), -OC(=0)(C3-C6halocycloalkyloxy), - C(=0)(CrC6alkyl), -C(=0)(Ci-C6haloalkyl),
Figure imgf000070_0001
- C(=0)(C2-C6alkenyl), -C(=0)(C2-C6haloalkenyl), -C(=0)(C2-C6alkenyloxy), -C(=0)(C2-
C6haloalkenyloxy), -C(=0)(C2-C6alkynyl), -C(=0)(C2-C6alkynyloxy), -C(=0)(C3-C6cycloalkyl), - C(=0)(C3-C6halocycloalkyl), -C(=0)(C3-C6cycloalkyloxy), -C(=0)(C3-C6halocycloalkyloxy), - S(=0)2(Ci-C6alkyl), -S(=0)2(Ci-C6haloalkyl), -S(=0)2(Ci-C6alkoxy), -S(=0)2(Ci-C6haloalkoxy), -S(=0)2(C2-C6alkenyl), -S(=0)2(C2-C6haloalkenyl), -S(=0)2(C2-C6alkenyloxy), -S(=0)2(C2- C6haloalkenyloxy), -S(=0)2(C2-C6alkynyl), -S(=0)2(C2-C6alkynyloxy), -S(=0)2(C3- Cecycloalkyl), -S(=0)2(C3-C6halocycloalkyl), -S(=0)2(C3-C6cycloalkyloxy), -S(=0)2(C3- Cehalocycloalkyloxy),
Figure imgf000070_0002
Cehaloalkyl),
Figure imgf000070_0003
Figure imgf000070_0004
-N(S(=0)2(Ci-C6haloalkoxy))2, -NHS(=0)2(C2-C6alkenyl), - N(S(=0)2(C2-C6alkenyl))2, -NHS(=0)2(C2-C6haloalkenyl), -N(S(=0)2(C2-C6haloalkenyl))2, - NHS(=0)2(C2-C6alkenyloxy), -N(S(=0)2(C2-C6alkenyloxy))2, -NHS(=0)2(C2-C6haloalkenyloxy), -N(S(=0)2(C2-C6haloalkenyloxy))2, -NHS(=0)2(C2-C6alkynyl), -N(S(=0)2(C2-C6alkynyl))2, - NHS(=0)2(C2-C6alkynyloxy), -N(S(=0)2(C2-C6alkynyloxy))2, -NHS(=0)2(C3-C6cycloalkyl), - N(S(=0)2(C3-C6cycloalkyl))2, -NHS(=0)2(C3-C6halocycloalkyl), -N(S(=0)2(C3- C6halocycloalkyl))2, -NHS(=0)2(C3-C6cycloalkyloxy), -N(S(=0)2(C3-C6cycloalkyloxy))2, - NHS(=0)2(C3-C6halocycloalkyloxy), -N(S(=0)2(C3-C6halocycloalkyloxy))2, -CH(=NOC
C6alkyl), -C(=NO(Ci-C6alkyl))Ci-C6alkyl, -C(=NO(Ci-C6alkyl))C2-C6alkenyl, -C(=NO(C
C6alkyl))C2-C6alkynyl, -C(=NO(Ci-C6alkyl))C3-C6cycloalkyl, -CH(=NN(Ci-C6alkyl)2, - C(=NN(Ci-C6alkyl)2)Ci-C6alkyl, -C(=NN(Ci-C6alkyl)2)C2-C6alkenyl, -C(=NN(CrC6alkyl)2)C2- C6alkynyl, -C(=NN(Ci-C6alkyl)2)C3-C6cycloalkyl, aryl or heterocyclyl; or
two R6 linked to the same carbon atom can form a saturated 3- to 4-membered carbocyclic or heterocyclic ring;
L1 and L2 are independently a direct bond, -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2- z, -NR5-z, -NR5-C(R6)2-z, -C(R6)2-NR5-z, -NR5-C(R6)2-C(R6)2-z, -C(R6)2-NR5-C(R6)2-z, -C(R6)2- C(R6)2-NR5-z, -C(R6)2-0-z, -C(R6)2-0-C(R6)2-z, -C(R6)2-C(R6)2-0-z, in each case z indicates the bond that is connected to R3 or R4;
or a salt or a N-oxide thereof.
2. A compound according to claim 1 , wherein
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, d-C6alkyl or CrC6alkoxy;
R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, C C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3- C6halocycloalkyl, C3-C6cycloalkyloxy or C3-C6halocycloalkyloxy;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
3. A compound according to claim 1 , wherein
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, CrC6alkyl or CrC6alkoxy;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
4. A compound according to claim 1 , wherein
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen or d-C6alkyl;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)NH(CrC6alkyl), -C(=0)N(C C6alkyl)2 or -C(=0)heterocyclyl;
R4 is aryl or 5- to 6-membered aromatic heterocyclic ring system;
R5 is hydrogen or C C6alkyl;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkynyl or C3-C6cycloalkyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z;
L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
5. A compound according to claim 1 , wherein
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2, and b indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
R3 is -C(=0)NH(CrC6alkyl);
R4 is phenyl or thienyl;
R5 is hydrogen or methyl;
R6 is fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z;
L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
6. A compound according to claim 1 , wherein
X1 is O, S or a-CH=N-b, wherein a indicates the bond that is connected to C-R2,
indicates the bond that is connected to C-X3;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl; R3 is -C(=0)NH(CrC6alkyl);
R4 is phenyl or thienyl;
R5 is hydrogen or methyl;
L1 is -C(CH3)2-z;
L2 is CH2CH(0(CrC6alkyl))-z;
or a salt or a N-oxide thereof.
7. A compound according to claim 1 , wherein
X1 is S or CH=N;
X2 and X3 are independently O, S or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, d-C6alkyl or CrC6alkoxy;
R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, C C6haloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3- C6halocycloalkyl, C3-C6cycloalkyloxy or C3-C6halocycloalkyloxy;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z; or a salt or a N-oxide thereof.
8. A compound according to claim 1 , wherein
X1 is S or CH=N;
X2 is O or S;
X3 is O or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, CrC6alkyl or CrC6alkoxy; R6 is halogen, cyano, nitro, hydroxyl, amino, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, Ci- Cehaloalkoxy, CrC6alkylthio, CrC6haloalkylthio, C2-C6alkenyl, C2-C6haloalkenyl, C2- C6alkenyloxy, C2-C6haloalkenyloxy, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl, C3- C6halocycloalkyl, C3-C6cycloalkyloxy or C3-C6halocycloalkyloxy;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
9. A compound according to claim 1 , wherein
X1 is S or CH=N;
X2 is O or S;
X3 is O or NR5;
X4 is O or NR5;
R1 is hydrogen, CrC6alkyl or C3-C6cycloalkyl, in which the alkyl and cycloalkyi groups are optionally substituted by one or more R6;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)R6 or heterocyclyl;
R4 is C3-C6cycloalkyl, aryl or heterocyclyl, in which cycloalkyi, aryl and heterocyclyl are optionally substituted by one or more R6;
R5 is hydrogen, d-C6alkyl or CrC6alkoxy;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkynyloxy, C3-C6cycloalkyl;
L1 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
L2 is -C(R6)2-z, -C(R6)2-C(R6)2-z, -C(R6)2-C(R6)2-C(R6)2-z, -C(R6)2-NR5-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
10. A compound according to claim 1 , wherein
X1 is S or CH=N;
X2 is O or S;
X3 is O or NR5;
X4 is O or NR5;
R1 is hydrogen or CrC6alkyl;
R2 is a 5- to 6-membered aromatic heterocyclic ring system;
R3 is -C(=0)NH(CrC6alkyl), -C(=0)N(C C6alkyl)2 or -C(=0)heterocyclyl;
R4 is aryl or 5- to 6-membered aromatic heterocyclic ring system;
R5 is hydrogen or CrC6alkyl;
R6 is halogen, cyano, CrC6alkyl, CrC6haloalkyl, CrC6alkoxy, CrC6haloalkoxy, C2-C6alkynyl or C3-C6cycloalkyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z; L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
11. A compound according to claim 1 , wherein
X1 is S orCH=N;
X2 is O or S;
X3 isOorNH;
X4 is O or NH;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1 ,3,4]oxadiazolyl or 5-isoxazolyl;
R3 is -C(=0)NH(CrC6alkyl);
R4is phenyl orthienyl;
R6 is fluoro, chloro, cyano, methyl, trifluoromethyl, methoxy, ethynyl or cyclopropyl;
L1 is -C(R6)2-z or -C(R6)2-C(R6)2-z;
L2 is -C(R6)2-C(R6)2-z or -C(R6)2-0-z;
or a salt or a N-oxide thereof.
12. A compound according to claim 1 , wherein
X1 is S orCH=N;
X2isOorS;
X3 isOorNH;
X4isOorNH;
R1 is methyl;
R2 is 2-oxazolyl, 2-thiazolyl, 2-[1,3,4]oxadiazolyl or 5-isoxazolyl;
R3 is -C(=0)NH(CrC6alkyl);
R4is phenyl orthienyl;
L1 is -C(CH3)2-z;
L2 is CH2CH(0(CrC6alkyl))-z;
or a salt or a N-oxide thereof. l-a:
Figure imgf000075_0001
in which X1, X2, X3, X4, R2, R3, R4, L1 and L2 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
Figure imgf000076_0001
wherein X1, X2, X3, X4, R1, R3, R4, L1 and L2 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
c:
Figure imgf000076_0002
in which X2, X3, X4, R1, R2, R3, R4, L1 and L2 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
:
Figure imgf000076_0003
in which X2, X3, X4, R1, R2, R3, R4, L1 and L2 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
or a compound of formula l-e:
Figure imgf000076_0004
in which X1, X2, X3, X4, R1, R2, R3, R4 and L2 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
or a compound of formula l-f:
Figure imgf000077_0001
in which X1, X2, X3, X4, R1, R2, R4, L1 and are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
5
Figure imgf000077_0002
in which X1, X2, X3, X4, R1, R2, R3, R4 and L1 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,
h:
Figure imgf000077_0003
10 in which X1, X2, X3, X4, R1, R2, R3, L1 and L2 are as defined in anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof.
14. A composition comprising at least one compound as defined in any one of claims 1 to
15 12 and an agriculturally acceptable carrier, optionally comprising an adjuvant, and optionally comprising one or more additional pesticidally active compounds.
15. A method of controlling or preventing an infestation of plants, propagation material thereof, harvested crops or of non-living materials by phytopathogenic or spoilage
20 microorganisms or organisms potentially harmful to man, which comprises the application of a compound as defined in any one of claims 1 to 12, to the plant, to parts of the plants or to the locus thereof, to propagation material thereof or to any part of the non-living materials.
PCT/EP2014/062894 2013-07-22 2014-06-18 Microbiocidal heterocyclic derivatives WO2015010832A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP13177443.2 2013-07-22
EP13177443 2013-07-22

Publications (1)

Publication Number Publication Date
WO2015010832A1 true WO2015010832A1 (en) 2015-01-29

Family

ID=48795526

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2014/062894 WO2015010832A1 (en) 2013-07-22 2014-06-18 Microbiocidal heterocyclic derivatives

Country Status (1)

Country Link
WO (1) WO2015010832A1 (en)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9782408B2 (en) 2014-10-06 2017-10-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10570115B2 (en) 2016-09-30 2020-02-25 Vertex Pharmaceuticals Incorporated Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US10654829B2 (en) 2017-10-19 2020-05-19 Vertex Pharmaceuticals Incorporated Crystalline forms and compositions of CFTR modulators
US10738030B2 (en) 2016-03-31 2020-08-11 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10793547B2 (en) 2016-12-09 2020-10-06 Vertex Pharmaceuticals Incorporated Modulator of the cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US11179367B2 (en) 2018-02-05 2021-11-23 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for treating cystic fibrosis
US11253509B2 (en) 2017-06-08 2022-02-22 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
US11414439B2 (en) 2018-04-13 2022-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US11434201B2 (en) 2017-08-02 2022-09-06 Vertex Pharmaceuticals Incorporated Processes for preparing pyrrolidine compounds
US11465985B2 (en) 2017-12-08 2022-10-11 Vertex Pharmaceuticals Incorporated Processes for making modulators of cystic fibrosis transmembrane conductance regulator
US11517564B2 (en) 2017-07-17 2022-12-06 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008016643A2 (en) * 2006-08-01 2008-02-07 Cytokinetics, Incorporated Certain chemical entities, compositions, and methods
WO2013071169A1 (en) * 2011-11-11 2013-05-16 Nimbus Apollo, Inc. Acc inhibitors and uses thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008016643A2 (en) * 2006-08-01 2008-02-07 Cytokinetics, Incorporated Certain chemical entities, compositions, and methods
WO2013071169A1 (en) * 2011-11-11 2013-05-16 Nimbus Apollo, Inc. Acc inhibitors and uses thereof

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9782408B2 (en) 2014-10-06 2017-10-10 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10258624B2 (en) 2014-10-06 2019-04-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US11426407B2 (en) 2014-10-06 2022-08-30 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10758534B2 (en) 2014-10-06 2020-09-01 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US10738030B2 (en) 2016-03-31 2020-08-11 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US11186566B2 (en) 2016-09-30 2021-11-30 Vertex Pharmaceuticals Incorporated Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US10570115B2 (en) 2016-09-30 2020-02-25 Vertex Pharmaceuticals Incorporated Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US10793547B2 (en) 2016-12-09 2020-10-06 Vertex Pharmaceuticals Incorporated Modulator of the cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US11453655B2 (en) 2016-12-09 2022-09-27 Vertex Pharmaceuticals Incorporated Modulator of the cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
US11253509B2 (en) 2017-06-08 2022-02-22 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
US11517564B2 (en) 2017-07-17 2022-12-06 Vertex Pharmaceuticals Incorporated Methods of treatment for cystic fibrosis
US11434201B2 (en) 2017-08-02 2022-09-06 Vertex Pharmaceuticals Incorporated Processes for preparing pyrrolidine compounds
US10654829B2 (en) 2017-10-19 2020-05-19 Vertex Pharmaceuticals Incorporated Crystalline forms and compositions of CFTR modulators
US11155533B2 (en) 2017-10-19 2021-10-26 Vertex Pharmaceuticals Incorporated Crystalline forms and compositions of CFTR modulators
US11465985B2 (en) 2017-12-08 2022-10-11 Vertex Pharmaceuticals Incorporated Processes for making modulators of cystic fibrosis transmembrane conductance regulator
US11179367B2 (en) 2018-02-05 2021-11-23 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions for treating cystic fibrosis
US11414439B2 (en) 2018-04-13 2022-08-16 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator

Similar Documents

Publication Publication Date Title
ES2807849T3 (en) Oxadiazole derivatives microbicides
US10501425B2 (en) Microbiocidal oxadiazole derivatives
WO2015007451A1 (en) Microbiocidal heterobicyclic derivatives
US10640497B2 (en) Microbiocidal oxadiazole derivatives
ES2842550T3 (en) Microbiocide thiazole derivatives
WO2015010832A1 (en) Microbiocidal heterocyclic derivatives
BR112018013821B1 (en) OXADIAZOLE DERIVED COMPOUNDS MICROBIOCIDES, AGROCHEMICAL COMPOSITION COMPRISING THE SUCH COMPOUNDS, METHOD OF CONTROL OR PREVENTION OF INFESTATION OF USEFUL PLANTS BY PHYTOPATOGENIC MICROORGANISMS AND USE OF SUCH COMPOUNDS
TWI810412B (en) Microbiocidal thiazole derivatives
WO2015003879A1 (en) Microbiocidal heterobicylic derivatives
WO2015007453A1 (en) Microbiocidal heterobicyclic derivatives
WO2015003881A1 (en) Microbiocidal heterobicyclic derivatives
BR112020000463A2 (en) microbiocidal oxadiazole derivatives
WO2016087593A1 (en) Novel fungicidal quinolinylamidines
EP3356335B1 (en) Microbiocidal oxadiazole derivatives
ES2810752T3 (en) Oxadiazole derivatives microbicides
TW202039480A (en) Microbiocidal thiazole derivatives

Legal Events

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

Ref document number: 14730942

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14730942

Country of ref document: EP

Kind code of ref document: A1