TREA

MICROBIOCIDAL PYRAZOLE DERIVATIVES

Follow

Information

  • Patent Application
  • 20150031541
  • Publication Number
    20150031541
  • Date Filed
    February 27, 2013
    11 years ago
  • Date Published
    January 29, 2015
    9 years ago
Information
Abstract
Compounds of the formula (I) wherein the substituents are as defined in claim 1, are useful as a pesticides.
Description

The present invention relates to microbiocidal pyrazole derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity. The invention also relates to preparation of these pyrazole derivatives, to pyrazole derivatives used as intermediates in the preparation of these pyrazole derivatives, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the pyrazole derivatives, to preparation of these compositions and to use of the pyrazole 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 2007/014290, WO 2008/013622, WO 2008/013925, WO 2008/091580, WO 2008/091594 and WO 2009/055514.


The present invention provides compounds of formula I:




embedded image


wherein,


G1 and G2 are independently O or S;


T is CR10 or N;

Y1 and Y2 are independently CR11 or N;


n is 1 or 2;


p is 1 or 2, providing that when n is 2, p is 1;


R1 and R2 each independently are C1-C4alkyl, C3-C5cycloalkyl or C1-C4haloalkyl;


R3, R4, R5, R6, R7 and R8 each independently are hydrogen, C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl, providing that at least one of R3, R4, R5, R6, R7 or R8 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl;


R9 is C(═O)—OR12, C(═O)—NR12R13 or a 4- to 15-membered mono-, bi- or tricyclic, saturated, partially unsaturated or aromatic heterocyclic ringsystem optionally substituted by one or more R14;


R10 is hydrogen, halogen or hydroxyl;


R11 is hydrogen, halogen or cyano;


R12 is arylalkyl, heteroarylalkyl or a 4- to 11-membered mono- or bicyclic, saturated, partially unsaturated or aromatic carbocyclic ringsystem, wherein the arylalkyl, heteroarylalkyl and 4- to 11-membered carbocyclic ringsystem are optionally substituted by one or more R14;


R13 is hydrogen, C1-C4alkyl, C3-C5cycloalkyl or C1-C4alkoxy; each R14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C4alkyl, C3-C8cycloalkyl-C1-C4alkoxy, C3-C8cycloalkyl-C1-C4alkylthio, C1-C8alkoxy, C3-C8cycloalkoxy, C1-C8alkenyloxy, C2-C8alkynyloxy, C1-C8alkylthio, C1-C8alkylsulfonyl, C1-C8alkylsulfinyl, C3-C8cycloalkylthio, C3-C8cycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, arylsulfinyl, aryl-C1-C4alkyl, aryl-C1-C4alkoxy, aryl-C1-C4alkylthio, heterocyclyl, heterocycyl-C1-C4alkyl, heterocycyl-C1-C4alkoxy, heterocycyl-C1-C4alkylthio, NH(C1-C8alkyl), N(C1-C8alkyl)2, C1-C4alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2-C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R15; and


each R15 independently is halogen, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C1-C4haloalkoxy; or a salt or a N-oxide thereof.


For the avoidance of doubt, by the expression “providing that at least one of R3, R4, R5, R6, R7 or R8 is, C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl, it is intended herein that at least one of R3, R4, R5, R6, R7 or R8 is not hydrogen.


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 five 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, unless stated otherwise 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, iso-amyl or pivaloyl.


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 CH2Cl, CHCl2, CCl3, CH2F, CHF2, CF3, CF3CH2, CH3CF2, CF3CF2 or CCl3CCl2.


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.


Heteroaryl stands for aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member. Monocyclic and bicyclic aromatic ring systems are preferred, monocyclic ring systems are more preferred. For example, monocyclic heteoraryl may be a 5- to 7-membered aromatic ring containing one to three heteroatoms selected from oxygen, nitrogen and sulfur, more preferably selected from nitrogen and sulfur. Bicyclic heteroaryl may be a 9- to 11-membered bicyclic ring containing one to five heteroatoms, preferably one to three heteroatoms, selected from oxygen, nitrogen and sulfur. Examples 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, imiazothiazoyl, quinolinyl, quinoxalinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl, preferably pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thienyl thiazolyl or thiadiazolyl. Heteroaryl rings do not contain adjacent oxygen ring atoms, adjacent sulfur ring atoms or adjacent oxygen and sulfur ring atoms. A link to a heteroaryl group can be via a carbon atom or via a nitrogen atom.


Heterocyclyl is defined to include heteroaryl and in addition their saturated or partially unsaturated analogues. The different rings of bi- or tricyclic heterocyclic ring systems 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).


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 G1, G2, T, Y1, Y2, n, p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 with reference to compounds of formula I and other compounds of the invention carrying the same substituents. 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.


G1 and G2 are independently O or S.


G1 is preferably O.


G2 is preferably S.


T is CR10 or N, preferably CH or N, more preferably CH.


Y1 and Y2 are independently CR11 or N.


Y1 is preferably CH or N, more preferably N.


Y2 is preferably CH or N; more preferably CH.


n is 1 or 2, preferably 2.


p is 1 or 2, providing that when n is 2, p is 1, preferably p is 1.


R1 and R2 each independently are C1-C4alkyl, C3-C5cycloalkyl or C1-C4haloalkyl. Preferably R1 and R2 are each independently methyl or halomethyl, more preferably methyl, difluoromethyl or trifluoromethyl.


Preferably R1 is difluoromethyl or trifluoromethyl. Preferably R2 is methyl or difluoromethyl. In one group of compounds R1 is trifluoromethyl and R2 is methyl. In another group of compounds R1 and R2 are both difluoromethyl.


R3, R4, R5, R6, R7 and R8 each independently are hydrogen, C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl, providing that at least one of R3, R4, R5, R6, R7 or R8 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl. Preferably one of R3 and R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl or C1-C4haloalkylsulfonyl and R4, R6, R7 and R8 are hydrogen;


More preferably one of R3 and R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4alkylsulfonyl or C3-C5cycloalkylsulfonyl and R4, R6, R7 and R8 are hydrogen.


Even more preferably, one of R3 and R5 is C1-C4alkylsulfanyl, C1-C4alkylsulfanyl or C1-C4alkylsulfonyl and R4, R6, R7 and R8 are hydrogen.


R9 is C(═O)—OR12, C(═O)—NR12R13 or a 4- to 15-membered mono-, bi- or tricyclic, saturated, partially unsaturated or aromatic heterocyclic ringsystem optionally substituted by one or more R14. Preferably R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14. More preferably R9 is C(═O)—NR12R13 or a isoxazoline optionally substituted by one or more R14


R10 is hydrogen, halogen or hydroxyl; preferably hydrogen, fluoro or hydroxyl, more preferably hydrogen.


R11 is hydrogen, halogen or cyano; preferably hydrogen or cyano, more preferably hydrogen.


R12 is arylalkyl, heteroarylalkyl or a 4- to 11-membered mono- or bicyclic, saturated, partially unsaturated or aromatic carbocyclic ringsystem, wherein the arylalkyl, heteroarylalkyl and 4- to 11-membered carbocyclic ringsystem are optionally substituted by one or more R14. Preferably R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14. More preferably R12 is benzyl or a 10-membered bicyclic carbocyclic ringsystem, wherein the benzyl and 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14


R13 is hydrogen, C1-C4alkyl, C3-C5cycloalkyl or C1-C4alkoxy. Preferably R13 is hydrogen or C1-C4alkyl. More preferably R13 is hydrogen or methyl.


Each R14 is independently, halogen, cyano, amino, nitro, hydroxyl, mercapto, C1-C8 alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C4alkyl, C3-C8cycloalkyl-C1-C4alkyloxy, C3-C8cycloalkyl-C1-C4alkylthio, C1-C8alkoxy, C3-C8cycloalkyloxy, C2-C8alkenyloxy, C2-C8alkynyloxy, C1-C8alkylthio, C1-C8alkylsulfonyl, C1-C8alkylsulfinyl, C3-C8cycloalkylthio, C3-C8cycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, arylsulfinyl, aryl-C1-C4alkyl, aryl-C1-C4alkoxy, aryl-C1-C4alkylthio, heterocyclyl, heterocycyl-C1-C4alkyl, heterocycyl-C1-C4alkoxy, heterocycyl-C1-C4alkylthio, NH(C1-C8alkyl), N(C1-C8alkyl)2, C1-C4alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2-C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein the aryl and heterocyclyl are optionally substituted by one or more R15.


Preferably each R14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, C1-C8 alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C4alkyl, C3-C8cycloalkyl-C1-C4alkylthio, C3-C8alkoxy, C3-C8cycloalkoxy, C2-C8alkenyloxy, C2-C8alkynyloxy, C1-C8alkylthio, C1-C8alkylsulfonyl, C1-C8alkylsulfinyl, C3-C8cycloalkylthio, C3-C8cycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, phenyl, phenyloxy, phenylthio, phenylsulfonyl, phenylsulfinyl, phenyl-C1-C4alkyl, phenyl-C1-C4alkyloxy, phenyl-C1-C4alkylthio, heterocyclyl, heterocycyl-C1-C4alkyl, heterocycyl-C1-C4alkyloxy, heterocycyl-C1-C4alkylthio, NH(C1-C8alkyl), N(C1-C8alkyl)2, C1-C4alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2-C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R15; and wherein heterocyclyl is independently selected from pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thienyl, thiazolyl, thiadiazolyl, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, and tetrahydropyranyl.


More preferably each R14 independently is halogen, cyano, amino, mercapto, C1-C8alkyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C4alkyloxy, C3-C8cycloalkyl-C1-C4alkylthio, C1-C8alkoxy, C1-C8alkylthio, phenyl, phenyloxy, phenylthio, phenyl-C1-C4alkoxy, phenyl-C1-C4alkylthio, heterocyclyl, heterocyclyl-C1-C4alkoxy, heterocyclyl-C1-C4alkylthio, NH(C1-C8alkyl), N(C1-C8alkyl)2, and wherein heterocyclyl is independently selected from pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thienyl, thiazolyl, thiadiazolyl, pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, and tetrahydroyranyl, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl moieties are optionally substituted by one or more R15.


Even more preferably each R14 independently is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15.


Each R15 is independently halogen, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C1-C4haloalkoxy, preferably each R15 independently is halogen, cyano, methyl, halomethyl, methoxy or halomethoxy, more preferably each R15 independently is halogen, methyl or halomethyl.


The compound of the invention may be a compound of formula I-a




embedded image


wherein Z is selected from Z-1 to Z-12




embedded image


embedded image


and G1, G2, T, Y1, Y2, n, p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 are as defined for formula I. The preferred substituent definitions are the same as for compounds of formula I. Preferably Z is selected from Z-1, Z-4, Z-8, Z-10 and Z-12.


Preferably, in compounds according to formula I-a, R14 and R15 are independently C1-C4alkyl, C1-C4haloalkyl or halogen.


In one group of compounds of the invention G1 and G2 are independently O or S; T is CR10 or N; Y1 is N; Y2 is CR11 or N; n is 1 or 2; p is 1; R1 and R2 each independently are C1-C4alkyl, C3-C5cycloalkyl or C1-C4haloalkyl; one of R3 and R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl or C1-C4haloalkylsulfonyl; R4, R6, R7 and R8 are hydrogen; R9 is C(═O)—OR12, C(═O)—NR12R13 or a 4- to 15-membered mono-, bi- or tricyclic, saturated, partially unsaturated or aromatic heterocyclic ringsystem optionally substituted by one or more R14; R10 is hydrogen, halogen or hydroxyl; R11 is hydrogen, halogen or cyano; R12 is arylalkyl, heteroarylalkyl or a 4- to 11-membered mono- or bicyclic, saturated, partially unsaturated or aromatic carbocyclic ringsystem, wherein the arylalkyl, heteroarylalkyl and 4- to 11-membered carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen, C1-C4alkyl, C3-C5cycloalkyl or C1-C4alkoxy; each R14 independently is halogen, cyano, amino, nitro, hydroxyl, mercapto, C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C4alkyl, C3-C8cycloalkyl-C1-C4alkoxy, C3-C8cycloalkyl-C1-C4alkylthio, C1-C8alkoxy, C3-C8cycloalkoxy, C1-C8alkenyloxy, C2-C8alkynyloxy, C1-C8alkylthio, C1-C8alkylsulfonyl, C1-C8alkylsulfinyl, C3-C8cycloalkylthio, C3-C8cycloalkylsulfonyl, C3-C8cycloalkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, arylsulfinyl, aryl-C1-C4alkyl, aryl-C1-C4alkoxy, aryl-C1-C4alkylthio, heterocyclyl, heterocycyl-C1-C4alkyl, heterocycyl-C1-C4alkoxy, heterocycyl-C1-C4alkylthio, NH(C1-C8alkyl), N(C1-C8alkyl)2, C1-C4alkylcarbonyl, C3-C8cycloalkylcarbonyl, C2-C8alkenylcarbonyl, C2-C8alkynylcarbonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, alkenyloxy, alkynyloxy and cycloalkoxy are optionally substituted by halogen, and wherein aryl and heterocyclyl are optionally substituted by one or more R15; and


each R15 independently is halogen, cyano, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C1-C4haloalkoxy.


In another group of compounds of the invention G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R3 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl; R4, R5, R6, R7 and R8 are hydrogen; R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14; R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen or methyl; each R14 is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15 and R15 is halogen, methyl or halomethyl.


In another group of compounds of the invention G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R3 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl or C1-C4haloalkylsulfonyl; R4, R5, R6, R7 and R8 are hydrogen; R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14; R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen or methyl; each R14 is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15 and R15 is halogen, methyl or halomethyl.


In another group of compounds of the invention G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R3 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4alkylsulfonyl or C3-C5cycloalkylsulfonyl; R4, R5, R6, R7 and R8 are hydrogen; R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14; R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen or methyl; each R14 is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15 and R15 is halogen, methyl or halomethyl.


In another group of compounds of the invention G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl; R3, R4, R6, R7 and R8 are hydrogen; R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14; R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen or methyl; each R14 is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15 and R15 is halogen, methyl or halomethyl.


In another group of compounds of the invention G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl or C1-C4haloalkylsulfonyl; R3, R4, R6, R7 and R8 are hydrogen; R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14; R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen or methyl; each R14 is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15 and R15 is halogen, methyl or halomethyl.


In another group of compounds of the invention G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4alkylsulfonyl or C3-C5cycloalkylsulfonyl; R3, R4, R6, R7 and R8 are hydrogen; R9 is C(═O)—NR12R13 or a 5-membered heterocyclic ringsystem optionally substituted by one or more R14; R12 is arylalkyl or a 9- to 10-membered bicyclic carbocyclic ringsystem, wherein the arylalkyl and 9- to 10-membered bicyclic carbocyclic ringsystem are optionally substituted by one or more R14; R13 is hydrogen or methyl; each R14 is halogen, cyano, amino, mercapto, C1-C4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl-C1-C4alkylthio, C1-C4alkoxy, C1-C4alkylthio, phenyl and phenyloxy, and wherein alkyl, cycloalkyl and alkoxy are optionally substituted by halogen, and wherein phenyl is optionally substituted by one or more R15 and R15 is halogen, methyl or halomethyl.


In another group of compounds the compound of the invention is a compound of formula I.a, wherein G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; Z is selected from Z-1 to Z12 (above); preferably Z-1, Z-4, Z-8, Z-10 and Z-12; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R3 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)-C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl and R4, R5, R6, R7 and R8 are hydrogen.


In another group of compounds the compound of the invention is a compound of formula I.a, wherein G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; Z is selected from Z-1 to Z-12 (above); preferably Z-1, Z-4, Z-8, Z-10 and Z-12; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R3 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl or C1-C4haloalkylsulfonyl; and R4, R5, R6, R7 and R8 are hydrogen.


In another group of compounds the compound of the invention is a compound of formula I.a, wherein G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; Z is selected from Z-1 to Z-12 (above); preferably Z-1, Z-4, Z-8, Z-10 and Z-12; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R3 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4alkylsulfonyl or C3-C5cycloalkylsulfonyl; and R4, R5, R6, R7 and R8 are hydrogen.


In another group of compounds the compound of the invention is a compound of formula I.a, wherein G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; Z is selected from Z-1 to Z-12 (above); preferably Z-1, Z-4, Z-8, Z-10 and Z-12; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl, —S(O)q(NQ)C1-C4alkyl, —S(O)q(NQ)C3-C5cycloalkyl, —S(O)q(NQ)-C1-C4haloalkyl, —SO2(NQ)C1-C4alkyl, —SO2(NQ)C1-C4cycloalkyl, —SO2(NQ)C1-C4haloalkyl, wherein q is 0 or 1 and Q is hydrogen, C1-C4alkyl or C1-C4alkylcarbonyl and R3, R4, R6, R7 and R8 are hydrogen.


In another group of compounds the compound of the invention is a compound of formula I.a, wherein G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; Z is selected from Z-1 to Z-12 (above); preferably Z-1, Z-4, Z-8, Z-10 and Z-12; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanynl, C1-C4haloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl; and R3, R4, R6, R7 and R8 are hydrogen.


In another group of compounds the compound of the invention is a compound of formula I.a, wherein G1 is O; G2 is S; T is CH or N; Y1 is N; Y2 is CH; Z is selected from Z-1 to Z-12 (above); preferably Z-1, Z-4, Z-8, Z-10 and Z-12; n is 2; p is 1; R1 is difluoromethyl or trifluoromethyl; R2 is methyl or difluoromethyl; R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4alkylsulfonyl or C3-C5cycloalkylsulfonyl; and R3, R4, R6, R7 and R8 are hydrogen.


For the avoidance of doubt, when n is 1 and p is 1 compounds of formula I have the formula according to formula I-b:




embedded image


in which R1, R2, R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1 and Y2 have the definitions as described for formula I.


When n is 2 and p is 1, compounds of formula I have the formula according to formula I-c:




embedded image


in which R1, R2, R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1 and Y2 have the definitions as described for formula I.


When n is 1 and p is 2, compounds of formula I have the formula according to formula I-d:




embedded image


in which R1, R2, R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1 and Y2 have the definitions as described for formula I.


The invention also relates to compounds of formula I-b, formula I-c and formula I-d as shown above.


The invention also relates to compounds of formula I-e:




embedded image


in which R1, R2, R3, R4, R5, R6, R7, R8, R9, G2, Y1 and Y2 have the definitions as described for formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, R9, G2, Y1 and Y2 are as defined for formula I.


The invention also relates to compounds of formula I-f:




embedded image


in which R1, R2, R3, R4, R5, R6, R7, R8 and R9 have the definitions as described for formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined for formula I.


The invention also relates to compounds of formula I-g:




embedded image


wherein R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1, Y2, n and p have the definition as described for formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention also relates to compounds of formula I-h:




embedded image


in which R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1, Y2, n and p have the definitions as described for formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, G1, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention includes compounds of formula II:




embedded image


wherein R3, R4, R5, R6, R7, R8, R9, G2, T, Y1, Y2, n and p are as defined for a compound of formula I and R16 is hydrogen, a protecting group, such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R3, R4, R5, R6, R7, R8, R9, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention also includes compounds of formula III




embedded image


wherein E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl; or group M,




embedded image


R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for a compound of formula I and R17 is C1-C6alkyl. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention also includes compounds of formula IV




embedded image


wherein E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl; or group M




embedded image


and R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for a compound of formula I. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention also includes compounds of formula V




embedded image


wherein E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl; or group M,




embedded image


R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for a compound of formula I and Hal is halogen, preferably chloro. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention also includes compounds of formula VI




embedded image


wherein E is hydrogen, a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl; or group M




embedded image


and R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for a compound of formula I. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R1, R2, R3, R4, R5, R6, R7, R8, G1, G2, T, Y1, Y2, n and p are as defined for formula I.


The invention also includes compounds of formula VII




embedded image


wherein E is hydrogen or a protecting group such as alkylcarbonyl, benzyl or alkoxycarbonyl, e.g. C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert-butoxycarbonyl; and R3, R4, R5, R7, R8, R9, G2, Y1, Y2, n and p are as defined for a compound of formula I. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of and R1, R2, R3, R4, R5, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I.


Preferred individual compounds of formula I are:

  • 4-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidine-3-methylsulfinyl;
  • 4-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidine-2-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-piperidine-3-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-piperidine-2-methylsulfinyl;
  • 4-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazine-2-methylsulfinyl;
  • 1-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-4-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazine-2-methylsulfinyl;
  • 4-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-1-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-piperazine-2-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-[4-(2-chloro-6-fluoro-benzyloxycarbonyl)-thiazol-2-yl]-piperazine-2-methylsulfinyl;
  • 4-{4-[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-thiazol-2-yl}-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidine-3-methylsulfinyl;
  • 4-{4-[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-thiazol-2-yl}-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidine-2-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-{4-[methyl-(1,2,3,4-tetrahydro-naphthalen 1-yl)-carbamoyl]-thiazol-2-yl}-piperidine-3-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-[4-[-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-thiazol-2-yl]-piperidine-2-methylsulfinyl;
  • 1-{4-[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-thiazol-2-yl}-4-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazine-2-methylsulfinyl;
  • 4-{4-[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-thiazol-2-yl}-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazine-2-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-{4-[methyl-(1,2,3,4-tetrahydronaphthalen-1-yl)-carbamoyl]-thiazol-2-yl}-piperazine-2-methylsulfinyl;
  • 4-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-1-{4-[methyl-(1,2,3,4-tetrahydronaphthalen-1-yl)-carbamoyl]-thiazol-2-yl}-piperazine-2-methylsulfinyl;
  • 4-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidine-3-methylsulfinyl;
  • 4-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidine-2-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-piperidine-3-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-piperidine-2-methylsulfinyl;
  • 1-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-4-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazine-2-methylsulfinyl;
  • 4-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazine-2-methylsulfinyl;
  • 1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-4-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-piperazine-2-methylsulfinyl; and
  • 4-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-1-{4-[5-(2,6-difluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2-yl}-piperazine-2-methylsulfinyl.


Compounds of the present invention can be made as shown in the following schemes. Throughout this description, the group M, wherein R1, R2 and G1 are as defined for formula I, stands for:




embedded image


The compounds of formula IX, wherein R3, R4, R5, R6, R7, R8, R12, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula V, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I, Hal is halogen, preferably chloro, and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a compound of formula VIII, wherein R12 is as defined for formula I and a base, such as pyridine, triethylamine, ethyl diisopropylamine. This is shown in Scheme 1.




embedded image


The compounds of formula V, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I, Hal is halogen, preferably chloro, and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula IV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a thionyl halide, such as thionyl chloride, or a phosphoryl halide, such as phosphoryl chloride. This is shown in Scheme 2.




embedded image


The compounds of formula IV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula III, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I, R17 is C1-C6alkyl and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a base, such as lithium hydroxide, sodium hydroxide, sodium carbonate, potassium hydroxide or potassium carbonate. This is shown in Scheme 3.




embedded image


Alternatively, the compounds of formula IX, wherein R3, R4, R5, R6, R7, R8, R12, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula IV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a compound of formula VIII, wherein R12 is as defined for formula I and an acid, such as hydrochloric acid or sulphuric acid. This is shown in Scheme 4.




embedded image


The compounds of formula XI, wherein R3, R4, R5, R6, R7, R8, R12, R13, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula V, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I, Hal is halogen, preferably chloro, and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a compound of formula X, wherein R12 and R13 are as defined for formula I and a base, such as pyridine, triethylamine, ethyl diisopropylamine. This is shown in Scheme 5.




embedded image


Alternatively, the compounds of formula XI, wherein R3, R4, R5, R6, R7, R8, R12, R13, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula IV, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a compound of formula X, wherein R12 and R13 are as defined for formula I, an activating reagent, such as BOP, PyBOP, EDCI, CDI or HATU, and a base, such as pyridine, triethylamine, ethyl diisopropylamine. This is shown in Scheme 6.




embedded image


The compounds of formula XIII, wherein R3, R4, R5, R6, R7, R8, R14, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, can be obtained by transformation of a compound of formula VI, wherein R3, R4, R5, R6, R7, R8, G2, T, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a compound of formula XII, wherein R14 is as defined for formula, and hydroxylamine and sodium hypochlorite. This is shown in Scheme 7.




embedded image


The compounds of formula XIV, wherein R3, R4, R5, R6, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula VII, wherein R3, R4, R5, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen or a protecting group such as acetyl, benzyl or tert-butoxycarbonyl, with hydrogen and a catalyst, such as palladium on charcoal or Raney-nickel, or with a hydride, such as lithium aluminium hydride. This is shown in Scheme 8.




embedded image


The compounds of formula VII, wherein R3, R4, R5, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen or a protecting group such as acetyl, benzyl or tert-butoxycarbonyl, can be obtained by transformation of a compound of formula XV, wherein R3, R4, R5, R7, R8, n and p are as defined for formula I, and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl, with a compound of formula XVI, wherein R9, G2, Y1, Y2 and Hal is halogen, preferably bromo or iodo, and a super base such as isopropylmagnesium chloride lithium chloride, followed by acid treatment. This is shown in Scheme 9.




embedded image


The compounds of formula XVII, wherein R3, R4, R6, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, R18 is alkyl, cyclohalkyl or haloalkyl and r is 1 or 2, can be obtained by transformation of a compound of formula XVIII, wherein R3, R4, R6, R7, R8, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M and R18 is alkyl, cyclohalkyl or haloalkyl, with an oxidant such as meta-chloroperbenzoic acid or sodium periodate. This is shown in Scheme 10.




embedded image


The compounds of formula XVIII, wherein R3, R4, R5, R6, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M and R18 is alkyl, cyclohalkyl or haloalkyl, can be obtained by transformation of a compound of formula XIX, wherein R3, R4, R6, R7, R8, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M and R18 is alkyl, cyclohalkyl or haloalkyl, with hydrogen and a catalyst, such as palladium on charcoal or Raney-nickel, or with a hydride, such as lithium aluminium hydride. This is shown in Scheme 11.




embedded image


The compounds of formula XIX, wherein R3, R4, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M and R18 is alkyl, cyclohalkyl or haloalkyl, can be obtained by transformation of a compound of formula XX, wherein R3, R4, R7, R8, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with anhydride wherein R19 is C1-C4alkyl or C1-C4haloalkyl such as triflic anhydride and then with alkylsulfanyl sodium, wherein R18 is alkyl, cycloalkyl or haloalkyl, such as methylsulfanyl sodium. This is shown in Scheme 12.




embedded image


Alternatively, the compounds of formula XIX, wherein R3, R4, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen or a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group, can be obtained by transformation of a compound of formula XXI, wherein R3, R4, R7, R8, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M and R18 is alkyl, cyclohalkyl or haloalkyl, with Lawesson's reagent and then alkyl iodide wherein R18 is alkyl, cyclohalkyl or haloalkyl. This is shown in Scheme 13.




embedded image


The compounds of formula XXI, wherein R3, R4, R7, R8, R9, G2, Y1, Y2, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group, can be obtained by transformation of a compound of formula XXII, wherein R3, R4, R7, R8, n and p are as defined for formula I and E is hydrogen, a protecting group such as acetyl, benzyl or tert-butoxycarbonyl or a group M, with a compound of formula XVI, wherein R9, G2, Y1, Y2 and Hal is halogen, preferably bromo or iodo, and a base or a catalyst such as copper iodide, a ligand. This is shown in Scheme 14.




embedded image


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 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 the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Alternaria spp.), Basidiomycetes (e.g. Corticium spp., Ceratobasidium spp., Waitea spp., Thanatephorus spp., Rhizoctonia spp., Hemileia spp., Puccinia spp., Phakopsora spp., Ustilago spp., Tilletia spp.), Ascomycetes (e.g. Venturia spp., Blumeria spp., Erysiphe spp., Podosphaera spp., Uncinula spp., Monilinia spp., Sclerotinia spp., Colletotrichum spp., Glomerella spp., Fusarium spp., Gibberella spp., Monographella spp., Phaeosphaeria spp., Mycosphaerella spp., Cercospora spp., Pyrenophora spp., Rhynchosporium spp., Magnaporthe spp., Gaeumannomyces spp., Oculimacula spp., Ramularia spp., Botryotinia spp.) and Oomycetes (e.g. Phytophthora spp., Pythium spp., Plasmopara spp., Peronospora spp., Pseudoperonospora spp. Bremia spp). Outstanding activity is observed against downy mildew (e.g. Plasmopara viticola) and late blight (e.g. Phytophthora infestans). Furthermore, the novel compounds of formula I are effective against phytopathogenic gram negative and gram positive bacteria (e.g. Xanthomonas spp, Pseudomonas spp, Erwinia amylovora, Ralstonia spp.) and viruses (e.g. tobacco mosaic virus).


Within the scope of present invention, target crops and/or useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as turf and ornamentals.


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 also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.


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” of a plant as used herein is intended to embrace the place on which the plants are growing, where the plant propagation materials of the plants are sown or where the plant propagation materials of the plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.


The term “plant propagation material” is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably “plant propagation material” is understood to denote seeds.


The compounds of formula I 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: Azoxystrobin (131860-33-8), Dimoxystrobin (149961-52-4), Enestrobin (238410-11-2), Fluoxastrobin (193740-76-0), Kresoxim-methyl (143390-89-0), Metominostrobin (133408-50-1), Orysastrobin (248593-16-0), Picoxystrobin (117428-22-5), Pyraclostrobin (175013-18-0), trifloxystrobin (141517-21-7), Azaconazole (60207-31-0), Bromuconazole (116255-48-2), Cyproconazole (94361-06-5), Difenoconazole (119446-68-3), Diniconazole (83657-24-3), Diniconazole-M (83657-18-5), Epoxiconazole (13385-98-8), Fenbuconazole (114369-43-6), Fluquinconazole (136426-54-5), Flusilazole (85509-19-9), Flutriafol (76674-21-0), Hexaconazole (79983-71-4), Imazalil (58594-72-2), Imibenconazole (86598-92-7), Ipconazole (125225-28-7), Metconazole (125116-23-6), Myclobutanil (88671-89-0), Oxpoconazole (174212-12-5), Pefurazoate (58011-68-0), Penconazole (66246-88-6), Prochloraz (67747-09-5), Propiconazole (60207-90-1), Prothioconazole (178928-70-6), Simeconazole (149508-90-7), Tebuconazole (107534-96-3), Tetraconazole (112281-77-3), Triadimefon (43121-43-3), Triadimenol (55219-65-3), Triflumizole (99387-89-0), Triticonazole (131983-72-7), Diclobutrazol (76738-62-0), Etaconazole (60207-93-4), Fluconazole (86386-73-4), Fluconazole-cis (112839-32-4), Thiabendazole (148-79-8), Quinconazole (103970-75-8), Fenpiclonil (74738-17-3), Fludioxonil (131341-86-1), Cyprodinil (121552-61-2), Mepanipyrim (110235-47-7), Pyrimethanil (53112-28-0), Aldimorph (91315-15-0), Dodemorph (1593-77-7), Fenpropimorph (67564-91-4), Tridemorph (81412-43-3), Fenpropidin (67306-00-7), Spiroxamine (118134-30-8), Isopyrazam (881685-58-1), Sedaxane (874967-67-6), Bixafen (581809-46-3), Penthiopyrad (183675-82-3), Fluxapyroxad (907204-31-3), Boscalid (188425-85-6), Penflufen (494793-67-8), Fluopyram (658066-35-4), Mandipropamid (374726-62-2), Benthiavalicarb (413615-35-7), Dimethomorph (110488-70-5), Chlorothalonil (1897-45-6), Fluazinam (79622-59-6), Dithianon (3347-22-6), Metrafenone (220899-03-6), Tricyclazole (41814-78-2), Mefenoxam (70630-17-0), Metalaxyl (57837-19-1), Acibenzolar (126448-41-7) (Acibenzolar-S-methyl (126448-41-7)), Mancozeb (8018-01-7), Ametoctradine (865318-97-4) Cyflufenamid (180409-60-3), and Kresoxim-methyl (143390-89-0), Ipconazole (125225-28-7), Amisulbrom (348635-87-0), Cyflufenamid (180409-60-3), Ethaboxam (16650-77-3), Fluopicolide (239110-15-7), Fluthianil (304900-25-2), Isotianil (224049-04-1), Proquinazid (189278-12-4), Valiphenal (283159-90-0), 1-methyl-cyclopropene (3100-04-7), Trifloxystrobin (141517-21-7), Sulfur (7704-34-9), Copper ammoniumcarbonate (CAS 33113-08-5); Copper oleate (CAS 1120-44-1); Folpet (133-07-3), Quinoxyfen (124495-18-7), Captan (133-06-2), Fenhexamid (126833-17-8), Glufosinate and its salts (51276-47-2, 35597-44-5 (S-isomer)), Glyphosate (1071-83-6) and its salts (69254-40-6 (Diammonium), 34494-04-7 (Dimethylammonium), 38641-94-0 (Isopropylammonium), 40465-66-5 (Monoammonium), 70901-20-1 (Potassium), 70393-85-0 (Sesquisodium), 81591-81-3 (Trimesium)), 1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide (1072957-71-1), 1-methyl-3-difluoromethyl-1H-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.


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 mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides, 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 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 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 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, 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. 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).


The agrochemical formulations and/or compositions will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula 1, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.


Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seed drenching agent, convenient dosages are from 10 mg to 1 g of active substance per kg of seeds.


Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.


The following non-limiting example illustrates the above-described invention in more detail.







EXAMPLE 1
This example illustrates the preparation of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.007)
a) Preparation of tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyridine-1-carboxylate

To a solution of N-isopropylpropan-2-amine (16.9 mL, 0.12 mol) in tetrahydrofuran (240 mL) added n-butyllithium (7.45 g, 0.12 mol) (2M Solution in tetrahydrofuran) at −10° C., stirred for 30 min. The resulted lithium di-isopropylamine solution was added drop wise to a solution of tert-butyl 4-oxopiperidine-1-carboxylate (20.0 g, 0.10 mol) in tetrahydrofuran (100 mL) at −78° C. After stirring for 2 h at the same temperature, a solution of 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (39.4 g, 0.11 mol) in tetrahydrofuran (780 mL) was added to the reaction mixture and stirred for 5 h at −70° C. Reaction mixture was concentrated under reduced pressure. The obtained crude product was purified by combi flash (eluting with 3% ethylacetate:n-hexane) to get 11 g of tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyridine-1-carboxylate. MS: m/z=332 (M+1).


b) Preparation of tert-butyl 4-cyano-3,6-dihydro-2H-pyridine-1-carboxylate

To a solution of tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyridine-1-carboxylate (6.0 g, 0.018 mol) in dimethyl sulphoxide (60 mL), palladium(0) tetrakis(triphenylphosphine) (0.84 g, 0.007 mmol) and zinc cyanide (3.81 g, 0.032 mol) was added. The reaction mixture was heated to 100° C. for 2 hr. The reaction mixture was diluted with water extracted with ethyl acetate. The organic layer was washed with water, followed by brine further dried over sodium sulphate and evaporated. The residue is purified by combi flash (eluting with 5% ethylacetate:n-hexane) to get 3.5 g of tert-butyl 4-cyano-3,6-dihydro-2H-pyridine-1-carboxylate. MS: m/z=209 (M+1).


c) Preparation of tert-butyl 4-cyano-3-methylsulfanyl-piperidine-1-carboxylate

To a solution of tert-butyl 4-cyano-3,6-dihydro-2H-pyridine-1-carboxylate (0.75 g, 0.0036 mol) in methanol (22 mL) added methanethiol sodium salt (0.29 g, 0.004 mol) at 0° C. and stirred at room temperature for 3 hrs. Methanol was evaporated under reduced pressure and diluted with ethyl acetate. Organic layer was washed with water, brine dried over sodium sulphate and evaporated. The residue was purified by combiflash (eluting with 10% ethylacetate:n-hexane) to give 393 mg of tert-butyl 4-cyano-3-methylsulfanyl-piperidine-1-carboxylate. MS: m/z=157 (M-100).


d) Preparation of 3-methylsulfanylpiperidine-4-carbonitrile hydrochloride

To a solution of tert-butyl 4-cyano-3-methylsulfanyl-piperidine-1-carboxylate (1.00 g, 0.003 mol) in methanol (4 mL) added 4 M hydrochloric acid in dioxane (8 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 h. After completion of reaction (analysed by TLC) solvent was completely evaporated to afford 3-methylsulfanylpiperidine-4-carbonitrile hydrochloride salt that was used as such for the next step.


e) Preparation of 3-methylsulfanyl-1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperidine-4-carbonitrile

To a solution of 2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetic acid (2.75 g, 0.013 mol) in N,N-dimethylforamide (22 mL), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridiniumare 3-oxid hexafluorophosphate (5.27 g, 0.014 mol), 3-methylsulfanylpiperidine-4-carbonitrile hydrochloride (2.55 g, 0.013 mol) and triethyl amine (5.52 mL, 0.04 mol) at 0° C. was added and allowed to stirred at room temperature for 3 hrs. After completion of reaction, the reaction mixture was diluted with water extracted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulphate. Organic layer was concentrated to dryness. The residue was washed with diethyl ether afforded 3.5 g of 3-methylsulfanyl-1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperidine-4-carbonitrile.


MS: m/z=347 (M+1).


f) Preparation of 3-methylsulfanyl-1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperidine-4-carbothioamide

To a solution of 3-methylsulfanyl-1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperidine-4-carbonitrile (1.2 g, 0.003 mol) in N,N-dimethylformamide (7 mL) ammonium sulfide (1.9 g, 0.028 mmol) was added at room temperature and stirred for 24 hr. Reaction mixture was quenched with ice and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated. The crude product was purified by combiflash (eluting with 30% ethyl acetate: dichloromethane) afforded 800 mg of 3-methylsulfanyl-1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperidine-4-carbothioamide. MS: m/z=381 (M+1).


g) Preparation of (1E/Z)-3-chloro-N-hydroxy-2-oxo-propanimidoyl chloride

To a solution of 1,3-dichloropropan-2-one (3.0 g, 0.023 mol) in 2M hydrogen chloride in diethyl ether (15 mL) added tert-butyl nitrite (1.65 g, 0.016 mol) at 10° C. and stirred for 16 h at room temperature. Solvent was evaporated the obtained viscous material was triturated with 10% diethyl ether/n-hexane to get (1E/Z)-3-chloro-N-hydroxy-2-oxo-propanimidoyl chloride as light brown solid and that was used as such in next step.


h) Preparation of 2-chloro-1-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]ethanone

To a solution of (1E/Z)-3-chloro-N-hydroxy-2-oxo-propanimidoyl chloride (1.2 g, 0.007 mol) and 1,3-difluoro-2-vinyl-benzene (1.00 g, 0.007 mol) in acetonitrile (15 mL), sodium bicarbonate (1.19 g, 0.014 mol) was added in portion wise at 10° C. and stirred for 5 h at room temperature. Reaction mixture was diluted with ethyl acetate washed with water, brine dried over sodium sulphate. Organic layer was concentrated and residue was purified by combiflash (eluting with 10% ethyl acetate: n-hexane) afforded 2-chloro-1-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]ethanone. MS: m/z=260 (M+1).


i) Preparation of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.007)

A solution of 3-methylsulfanyl-1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperidine-4-carbothioamide (0.50 g, 0.001 mol) and 2-chloro-1-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]ethanone (0.30 g, 0.001 mol) in ethanol (15 mL) was heated to reflux for 5 hrs. Ethanol was evaporated, diluted with ethyl acetate, washed with water, brine, dried over sodium sulphate. Organic layer was concentrated and residue was purified by combiflash (eluting with 20-40% ethyl acetate: n-hexane) afforded 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.007) as mixture of diastereomer (280 mg). 1H-NMR (400 MHz, CDCl3): δ=1.80-2.40 (m, 8H), 3.30-3.45 (m, 2H), 3.60-3.90 (m, 4H), 4.10-4.20 (m, 1H), 4.50-4.70 (m, 1H), 4.90-5.10 (m, 1H), 5.15 (s, 1H), 6.00-6.15 (m, 1H), 6.33 (d, J=3.6 Hz, 1H), 6.92 (t, J=8.4 Hz, 2H), 7.30-7.40 (m, 1H), 7.68 (d, J=4 Hz, 1H).


MS: m/z=586.1 (M+1).


EXAMPLE 2
This example illustrates the preparation of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfinyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.008) and 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfonyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.009)

To a solution of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.007, 0.2 g, 0.003 mol) in chloroform (2 mL) sodium tungstate dihydrate (0.005 g, 0.02 mmol) and tetrabutylammonium hydrogen sulphate (0.01 g, 0.03 mmol) were added at −5° C. hydrogen peroxide (0.01 g, 0.4 mmol, 50% aqueous solution) was added and resulting reaction mixture was stirred for 20 min at −5° C. Reaction mixture was quenched with saturated sodiumthiosulphite solution and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate. The organic layer was concentrated. The crude product was purified by combiflash (eluting with 30-70% ethyl acetate/n-hexane and finally eluted with ethyl acetate for 10 min) to afford 30 mg of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfinyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.008) as mixture of diastereomer and 38 mg of 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfonyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.009) as mixture of diastereomer.


(compound I.az.008) 1H-NMR (400 MHz, CDCl3): δ=2.10-2.25 (m, 2H), 2.27 (s, 3H), 2.36 (d, J=3.2 Hz, 3H), 2.85-2.95 (m, 1H), 3.50-4.00 (m, 5H), 4.54 (d, J=13.6 Hz, 1H), 4.84 (d, J=12.8 Hz, 1H), 5.12 (d, J=16.4 Hz, 1H), 5.49 (d, J=16.4 Hz, 1H), 6.00-6.20 (m, 1H), 6.30 (s, 1H), 6.93 (t, J=8.4 Hz, 2H), 7.27-7.40 (m, 1H), 7.70 (d, J=4.0 Hz, 1H)


MS: m/z=602.0 (M+1).


(compound I.az.009) 1H-NMR (400 MHz, CDCl3): δ=2.00-2.40 (m, 5H), 2.62 (d, J=4.8 Hz, 3H), 3.10-3.30 (m, 1H), 3.50-3.85 (m, 4H), 3.90-4.00 (m, 1H), 4.10-4.50 (m, 1H), 4.60-5.00 (m, 1H), 5.10-5.40 (m, 2H), 6.00-6.20 (m, 1H), 6.32 (d, J=8.8 Hz, 1H), 6.92 (d, J=8.3 Hz, 2H), 7.30-7.40 (m, 1H), 7.60-7.80 (m, 1H).


MS: m/z=618.2 (M+1).


EXAMPLE 3
This example illustrates the preparation of 2-[3,5-bis(difluoromethyl)pyrazol-1-yl]-1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]ethanone (compound I.az.223)
a) Preparation of 1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-3-methylsulfanyl-piperidine-4-carbonitrile

To a solution of 2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetic acid (1.10 g, 4.90 mmol) in N, N-dimethylforamide (9 mL) 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridiniumare 3-oxid hexafluorophosphate (1.9 g, 5.10 mmol), 3-methylsulfanylpiperidine-4-carbonitrile hydrochloride (0.94 g, 4.90 mmol) and triethyl amine (2.1 mL, 15.0 mmol) was added at 0° C. and allowed to stirred at room temperature for 3 hrs. After completion of reaction, the reaction mixture was diluted with water extracted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulphate. Organic layer was concentrated to dryness. The residue was washed with diethyl ether afforded 1.1 g of 1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-3-methylsulfanyl-piperidine-4-carbonitrile. MS: m/z=365 (M+1).


b) Preparation of 1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-3-methylsulfanyl-piperidine-4-carbothioamide

To a solution of 1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-3-methylsulfanyl-piperidine-4-carbonitrile (1.0 g, 0.0027 mol) in N,N-dimethylformamide (6 mL) added ammonium sulfide (1.49 g, 0.021 mol) at room temperature and stirred for 24 hr. Reaction mixture was quenched with ice and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulphate and concentrated. The crude product was purified by combiflash (eluting with 30% ethyl acetate: dichloromethane) afforded 900 mg of 1-[2-10 [3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-3-methylsulfanyl-piperidine-4-carbothioamide.


MS: m/z=399 (M+1).


c) Preparation of 2-[3,5-bis(difluoromethyl)pyrazol-1-yl]-1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]ethanone (compound I.az.223)

A solution of 1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-3-methylsulfanyl-piperidine-4-carbothioamide (0.20 g, 0.50 mmol) and 2-chloro-1-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]ethanone (0.10 g, 0.6 mmol) in ethanol (6 mL) was heated to reflux for 5 hrs. Ethanol was evaporated, diluted with ethyl acetate, washed with water, brine, dried over sodium sulphate. Organic layer was concentrated and residue was purified by combiflash (eluting with 20-40% Ethyl acetate: n-hexane) afforded 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl]thiazol-2-yl]-3-methylsulfanyl-1-piperidyl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (compound I.az.223) as mixture of diastereomer (64 mg). 1H-NMR (400 MHz, CDCl3): δ=1.90-2.40 (m, 6H), 2.80-3.20 (m, 1H), 3.20-3.42 (m, 2H), 3.60-3.95 (m, 3H), 4.20-4.40 (m, 1H), 5.20-5.30 (m, 2H), 6.00-6.20 (m, 1H), 6.50-7.10 (m, 5H), 7.30-7.40 (m, 1H), 7.70 (m, 1H)


MS: m/z=604.3 (M+1).


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.






















No.
R1
R2
R3
R5
T
Y1
G2
Y2


















001
F3C
H3C
SCH3
H
CH
N
S
CH


002
F3C
H3C
S(O)CH3
H
CH
N
S
CH


003
F3C
H3C
SO2CH3
H
CH
N
S
CH


004
F3C
H3C
S(O)(NH)CH3
H
CH
N
S
CH


005
F3C
H3C
SO2N(H)CH3
H
CH
N
S
CH


006
F3C
H3C
S(O)CH2CH3
H
CH
N
S
CH


007
F3C
H3C
H
SCH3
CH
N
S
CH


008
F3C
H3C
H
S(O)CH3
CH
N
S
CH


009
F3C
H3C
H
SO2CH3
CH
N
S
CH


010
F3C
H3C
H
S(O)(NH)CH3
CH
N
S
CH


011
F3C
H3C
H
SO2N(H)CH3
CH
N
S
CH


012
F3C
H3C
H
S(O)CH2CH3
CH
N
S
CH


013
F3C
H3C
SCH3
H
CH
N
S
N


014
F3C
H3C
S(O)CH3
H
CH
N
S
N


015
F3C
H3C
SO2CH3
H
CH
N
S
N


016
F3C
H3C
S(O)(NH)CH3
H
CH
N
S
N


017
F3C
H3C
SO2N(H)CH3
H
CH
N
S
N


018
F3C
H3C
S(O)CH2CH3
H
CH
N
S
N


019
F3C
H3C
H
SCH3
CH
N
S
N


020
F3C
H3C
H
S(O)CH3
CH
N
S
N


021
F3C
H3C
H
SO2CH3
CH
N
S
N


022
F3C
H3C
H
S(O)(NH)CH3
CH
N
S
N


023
F3C
H3C
H
SO2N(H)CH3
CH
N
S
N


024
F3C
H3C
H
S(O)CH2CH3
CH
N
S
N


025
F3C
H3C
SCH3
H
CH
N
O
CH


026
F3C
H3C
S(O)CH3
H
CH
N
O
CH


027
F3C
H3C
SO2CH3
H
CH
N
O
CH


028
F3C
H3C
S(O)(NH)CH3
H
CH
N
O
CH


029
F3C
H3C
SO2N(H)CH3
H
CH
N
O
CH


030
F3C
H3C
S(O)CH2CH3
H
CH
N
O
CH


031
F3C
H3C
H
SCH3
CH
N
O
CH


032
F3C
H3C
H
S(O)CH3
CH
N
O
CH


033
F3C
H3C
H
SO2CH3
CH
N
O
CH


034
F3C
H3C
H
S(O)(NH)CH3
CH
N
O
CH


035
F3C
H3C
H
SO2N(H)CH3
CH
N
O
CH


036
F3C
H3C
H
S(O)CH2CH3
CH
N
O
CH


037
F3C
H3C
SCH3
H
N
N
S
CH


038
F3C
H3C
S(O)CH3
H
N
N
S
CH


039
F3C
H3C
SO2CH3
H
N
N
S
CH


040
F3C
H3C
S(O)(NH)CH3
H
N
N
S
CH


041
F3C
H3C
SO2N(H)CH3
H
N
N
S
CH


042
F3C
H3C
S(O)CH2CH3
H
N
N
S
CH


043
F3C
H3C
H
SCH3
N
N
S
CH


044
F3C
H3C
H
S(O)CH3
N
N
S
CH


045
F3C
H3C
H
SO2CH3
N
N
S
CH


046
F3C
H3C
H
S(O)(NH)CH3
N
N
S
CH


047
F3C
H3C
H
SO2N(H)CH3
N
N
S
CH


048
F3C
H3C
H
S(O)CH2CH3
N
N
S
CH


049
F3C
H3C
SCH3
H
N
N
S
N


050
F3C
H3C
S(O)CH3
H
N
N
S
N


051
F3C
H3C
SO2CH3
H
N
N
S
N


052
F3C
H3C
S(O)(NH)CH3
H
N
N
S
N


053
F3C
H3C
SO2N(H)CH3
H
N
N
S
N


054
F3C
H3C
S(O)CH2CH3
H
N
N
S
N


055
F3C
H3C
H
SCH3
N
N
S
N


056
F3C
H3C
H
S(O)CH3
N
N
S
N


057
F3C
H3C
H
SO2CH3
N
N
S
N


058
F3C
H3C
H
S(O)(NH)CH3
N
N
S
N


059
F3C
H3C
H
SO2N(H)CH3
N
N
S
N


060
F3C
H3C
H
S(O)CH2CH3
N
N
S
N


061
F3C
H3C
SCH3
H
N
N
O
CH


062
F3C
H3C
S(O)CH3
H
N
N
O
CH


063
F3C
H3C
SO2CH3
H
N
N
O
CH


064
F3C
H3C
S(O)(NH)CH3
H
N
N
O
CH


065
F3C
H3C
SO2N(H)CH3
H
N
N
O
CH


066
F3C
H3C
S(O)CH2CH3
H
N
N
O
CH


067
F3C
H3C
H
SCH3
N
N
O
CH


068
F3C
H3C
H
S(O)CH3
N
N
O
CH


069
F3C
H3C
H
SO2CH3
N
N
O
CH


070
F3C
H3C
H
S(O)(NH)CH3
N
N
O
CH


071
F3C
H3C
H
SO2N(H)CH3
N
N
O
CH


072
F3C
H3C
H
S(O)CH2CH3
N
N
O
CH


073
H3C
H3C
SCH3
H
CH
N
S
CH


074
H3C
H3C
S(O)CH3
H
CH
N
S
CH


075
H3C
H3C
SO2CH3
H
CH
N
S
CH


076
H3C
H3C
S(O)(NH)CH3
H
CH
N
S
CH


077
H3C
H3C
SO2N(H)CH3
H
CH
N
S
CH


078
H3C
H3C
S(O)CH2CH3
H
CH
N
S
CH


079
H3C
H3C
H
SCH3
CH
N
S
CH


080
H3C
H3C
H
S(O)CH3
CH
N
S
CH


081
H3C
H3C
H
SO2CH3
CH
N
S
CH


082
H3C
H3C
H
S(O)(NH)CH3
CH
N
S
CH


083
H3C
H3C
H
SO2N(H)CH3
CH
N
S
CH


084
H3C
H3C
H
S(O)CH2CH3
CH
N
S
CH


085
H3C
H3C
SCH3
H
CH
N
S
N


086
H3C
H3C
S(O)CH3
H
CH
N
S
N


087
H3C
H3C
SO2CH3
H
CH
N
S
N


088
H3C
H3C
S(O)(NH)CH3
H
CH
N
S
N


089
H3C
H3C
SO2N(H)CH3
H
CH
N
S
N


090
H3C
H3C
S(O)CH2CH3
H
CH
N
S
N


091
H3C
H3C
H
SCH3
CH
N
S
N


092
H3C
H3C
H
S(O)CH3
CH
N
S
N


093
H3C
H3C
H
SO2CH3
CH
N
S
N


094
H3C
H3C
H
S(O)(NH)CH3
CH
N
S
N


095
H3C
H3C
H
SO2N(H)CH3
CH
N
S
N


096
H3C
H3C
H
S(O)CH2CH3
CH
N
S
N


097
H3C
H3C
SCH3
H
CH
N
O
CH


098
H3C
H3C
S(O)CH3
H
CH
N
O
CH


099
H3C
H3C
SO2CH3
H
CH
N
O
CH


100
H3C
H3C
S(O)(NH)CH3
H
CH
N
O
CH


101
H3C
H3C
SO2N(H)CH3
H
CH
N
O
CH


102
H3C
H3C
S(O)CH2CH3
H
CH
N
O
CH


103
H3C
H3C
H
SCH3
CH
N
O
CH


104
H3C
H3C
H
S(O)CH3
CH
N
O
CH


105
H3C
H3C
H
SO2CH3
CH
N
O
CH


106
H3C
H3C
H
S(O)(NH)CH3
CH
N
O
CH


107
H3C
H3C
H
SO2N(H)CH3
CH
N
O
CH


108
H3C
H3C
H
S(O)CH2CH3
CH
N
O
CH


109
H3C
H3C
SCH3
H
N
N
S
CH


110
H3C
H3C
S(O)CH3
H
N
N
S
CH


111
H3C
H3C
SO2CH3
H
N
N
S
CH


112
H3C
H3C
S(O)(NH)CH3
H
N
N
S
CH


113
H3C
H3C
SO2N(H)CH3
H
N
N
S
CH


114
H3C
H3C
S(O)CH2CH3
H
N
N
S
CH


115
H3C
H3C
H
SCH3
N
N
S
CH


116
H3C
H3C
H
S(O)CH3
N
N
S
CH


117
H3C
H3C
H
SO2CH3
N
N
S
CH


118
H3C
H3C
H
S(O)(NH)CH3
N
N
S
CH


119
H3C
H3C
H
SO2N(H)CH3
N
N
S
CH


120
H3C
H3C
H
S(O)CH2CH3
N
N
S
CH


121
H3C
H3C
SCH3
H
N
N
S
N


122
H3C
H3C
S(O)CH3
H
N
N
S
N


123
H3C
H3C
SO2CH3
H
N
N
S
N


124
H3C
H3C
S(O)(NH)CH3
H
N
N
S
N


125
H3C
H3C
SO2N(H)CH3
H
N
N
S
N


126
H3C
H3C
S(O)CH2CH3
H
N
N
S
N


127
H3C
H3C
H
SCH3
N
N
S
N


128
H3C
H3C
H
S(O)CH3
N
N
S
N


129
H3C
H3C
H
SO2CH3
N
N
S
N


130
H3C
H3C
H
S(O)(NH)CH3
N
N
S
N


131
H3C
H3C
H
SO2N(H)CH3
N
N
S
N


132
H3C
H3C
H
S(O)CH2CH3
N
N
S
N


133
H3C
H3C
SCH3
H
N
N
O
CH


134
H3C
H3C
S(O)CH3
H
N
N
O
CH


135
H3C
H3C
SO2CH3
H
N
N
O
CH


136
H3C
H3C
S(O)(NH)CH3
H
N
N
O
CH


137
H3C
H3C
SO2N(H)CH3
H
N
N
O
CH


138
H3C
H3C
S(O)CH2CH3
H
N
N
O
CH


139
H3C
H3C
H
SCH3
N
N
O
CH


140
H3C
H3C
H
S(O)CH3
N
N
O
CH


141
H3C
H3C
H
SO2CH3
N
N
O
CH


142
H3C
H3C
H
S(O)(NH)CH3
N
N
O
CH


143
H3C
H3C
H
SO2N(H)CH3
N
N
O
CH


144
H3C
H3C
H
S(O)CH2CH3
N
N
O
CH


145
F2HC
H3C
SCH3
H
CH
N
S
CH


146
F2HC
H3C
S(O)CH3
H
CH
N
S
CH


147
F2HC
H3C
SO2CH3
H
CH
N
S
CH


148
F2HC
H3C
S(O)(NH)CH3
H
CH
N
S
CH


149
F2HC
H3C
SO2N(H)CH3
H
CH
N
S
CH


150
F2HC
H3C
S(O)CH2CH3
H
CH
N
S
CH


151
F2HC
H3C
H
SCH3
CH
N
S
CH


152
F2HC
H3C
H
S(O)CH3
CH
N
S
CH


153
F2HC
H3C
H
SO2CH3
CH
N
S
CH


154
F2HC
H3C
H
S(O)(NH)CH3
CH
N
S
CH


155
F2HC
H3C
H
SO2N(H)CH3
CH
N
S
CH


156
F2HC
H3C
H
S(O)CH2CH3
CH
N
S
CH


157
F2HC
H3C
SCH3
H
CH
N
S
N


158
F2HC
H3C
S(O)CH3
H
CH
N
S
N


159
F2HC
H3C
SO2CH3
H
CH
N
S
N


160
F2HC
H3C
S(O)(NH)CH3
H
CH
N
S
N


161
F2HC
H3C
SO2N(H)CH3
H
CH
N
S
N


162
F2HC
H3C
S(O)CH2CH3
H
CH
N
S
N


163
F2HC
H3C
H
SCH3
CH
N
S
N


164
F2HC
H3C
H
S(O)CH3
CH
N
S
N


165
F2HC
H3C
H
SO2CH3
CH
N
S
N


166
F2HC
H3C
H
S(O)(NH)CH3
CH
N
S
N


167
F2HC
H3C
H
SO2N(H)CH3
CH
N
S
N


168
F2HC
H3C
H
S(O)CH2CH3
CH
N
S
N


169
F2HC
H3C
SCH3
H
CH
N
O
CH


170
F2HC
H3C
S(O)CH3
H
CH
N
O
CH


171
F2HC
H3C
SO2CH3
H
CH
N
O
CH


172
F2HC
H3C
S(O)(NH)CH3
H
CH
N
O
CH


173
F2HC
H3C
SO2N(H)CH3
H
CH
N
O
CH


174
F2HC
H3C
S(O)CH2CH3
H
CH
N
O
CH


175
F2HC
H3C
H
SCH3
CH
N
O
CH


176
F2HC
H3C
H
S(O)CH3
CH
N
O
CH


177
F2HC
H3C
H
SO2CH3
CH
N
O
CH


178
F2HC
H3C
H
S(O)(NH)CH3
CH
N
O
CH


179
F2HC
H3C
H
SO2N(H)CH3
CH
N
O
CH


180
F2HC
H3C
H
S(O)CH2CH3
CH
N
O
CH


181
F2HC
H3C
SCH3
H
N
N
S
CH


182
F2HC
H3C
S(O)CH3
H
N
N
S
CH


183
F2HC
H3C
SO2CH3
H
N
N
S
CH


184
F2HC
H3C
S(O)(NH)CH3
H
N
N
S
CH


185
F2HC
H3C
SO2N(H)CH3
H
N
N
S
CH


186
F2HC
H3C
S(O)CH2CH3
H
N
N
S
CH


187
F2HC
H3C
H
SCH3
N
N
S
CH


188
F2HC
H3C
H
S(O)CH3
N
N
S
CH


189
F2HC
H3C
H
SO2CH3
N
N
S
CH


190
F2HC
H3C
H
S(O)(NH)CH3
N
N
S
CH


191
F2HC
H3C
H
SO2N(H)CH3
N
N
S
CH


192
F2HC
H3C
H
S(O)CH2CH3
N
N
S
CH


193
F2HC
H3C
SCH3
H
N
N
S
N


194
F2HC
H3C
S(O)CH3
H
N
N
S
N


195
F2HC
H3C
SO2CH3
H
N
N
S
N


196
F2HC
H3C
S(O)(NH)CH3
H
N
N
S
N


197
F2HC
H3C
SO2N(H)CH3
H
N
N
S
N


198
F2HC
H3C
S(O)CH2CH3
H
N
N
S
N


199
F2HC
H3C
H
SCH3
N
N
S
N


200
F2HC
H3C
H
S(O)CH3
N
N
S
N


201
F2HC
H3C
H
SO2CH3
N
N
S
N


202
F2HC
H3C
H
S(O)(NH)CH3
N
N
S
N


203
F2HC
H3C
H
SO2N(H)CH3
N
N
S
N


204
F2HC
H3C
H
S(O)CH2CH3
N
N
S
N


205
F2HC
H3C
SCH3
H
N
N
O
CH


206
F2HC
H3C
S(O)CH3
H
N
N
O
CH


207
F2HC
H3C
SO2CH3
H
N
N
O
CH


208
F2HC
H3C
S(O)(NH)CH3
H
N
N
O
CH


209
F2HC
H3C
SO2N(H)CH3
H
N
N
O
CH


210
F2HC
H3C
S(O)CH2CH3
H
N
N
O
CH


211
F2HC
H3C
H
SCH3
N
N
O
CH


212
F2HC
H3C
H
S(O)CH3
N
N
O
CH


213
F2HC
H3C
H
SO2CH3
N
N
O
CH


214
F2HC
H3C
H
S(O)(NH)CH3
N
N
O
CH


215
F2HC
H3C
H
SO2N(H)CH3
N
N
O
CH


216
F2HC
H3C
H
S(O)CH2CH3
N
N
O
CH


217
F2HC
F2HC
SCH3
H
CH
N
S
CH


218
F2HC
F2HC
S(O)CH3
H
CH
N
S
CH


219
F2HC
F2HC
SO2CH3
H
CH
N
S
CH


220
F2HC
F2HC
S(O)(NH)CH3
H
CH
N
S
CH


221
F2HC
F2HC
SO2N(H)CH3
H
CH
N
S
CH


222
F2HC
F2HC
S(O)CH2CH3
H
CH
N
S
CH


223
F2HC
F2HC
H
SCH3
CH
N
S
CH


224
F2HC
F2HC
H
S(O)CH3
CH
N
S
CH


225
F2HC
F2HC
H
SO2CH3
CH
N
S
CH


226
F2HC
F2HC
H
S(O)(NH)CH3
CH
N
S
CH


227
F2HC
F2HC
H
SO2N(H)CH3
CH
N
S
CH


228
F2HC
F2HC
H
S(O)CH2CH3
CH
N
S
CH


229
F2HC
F2HC
SCH3
H
CH
N
S
N


230
F2HC
F2HC
S(O)CH3
H
CH
N
S
N


231
F2HC
F2HC
SO2CH3
H
CH
N
S
N


232
F2HC
F2HC
S(O)(NH)CH3
H
CH
N
S
N


233
F2HC
F2HC
SO2N(H)CH3
H
CH
N
S
N


234
F2HC
F2HC
S(O)CH2CH3
H
CH
N
S
N


235
F2HC
F2HC
H
SCH3
CH
N
S
N


236
F2HC
F2HC
H
S(O)CH3
CH
N
S
N


237
F2HC
F2HC
H
SO2CH3
CH
N
S
N


238
F2HC
F2HC
H
S(O)(NH)CH3
CH
N
S
N


239
F2HC
F2HC
H
SO2N(H)CH3
CH
N
S
N


240
F2HC
F2HC
H
S(O)CH2CH3
CH
N
S
N


241
F2HC
F2HC
SCH3
H
CH
N
O
CH


242
F2HC
F2HC
S(O)CH3
H
CH
N
O
CH


243
F2HC
F2HC
SO2CH3
H
CH
N
O
CH


244
F2HC
F2HC
S(O)(NH)CH3
H
CH
N
O
CH


245
F2HC
F2HC
SO2N(H)CH3
H
CH
N
O
CH


246
F2HC
F2HC
S(O)CH2CH3
H
CH
N
O
CH


247
F2HC
F2HC
H
SCH3
CH
N
O
CH


248
F2HC
F2HC
H
S(O)CH3
CH
N
O
CH


249
F2HC
F2HC
H
SO2CH3
CH
N
O
CH


250
F2HC
F2HC
H
S(O)(NH)CH3
CH
N
O
CH


251
F2HC
F2HC
H
SO2N(H)CH3
CH
N
O
CH


252
F2HC
F2HC
H
S(O)CH2CH3
CH
N
O
CH


253
F2HC
F2HC
SCH3
H
N
N
S
CH


254
F2HC
F2HC
S(O)CH3
H
N
N
S
CH


255
F2HC
F2HC
SO2CH3
H
N
N
S
CH


256
F2HC
F2HC
S(O)(NH)CH3
H
N
N
S
CH


257
F2HC
F2HC
SO2N(H)CH3
H
N
N
S
CH


258
F2HC
F2HC
S(O)CH2CH3
H
N
N
S
CH


259
F2HC
F2HC
H
SCH3
N
N
S
CH


260
F2HC
F2HC
H
S(O)CH3
N
N
S
CH


261
F2HC
F2HC
H
SO2CH3
N
N
S
CH


262
F2HC
F2HC
H
S(O)(NH)CH3
N
N
S
CH


263
F2HC
F2HC
H
SO2N(H)CH3
N
N
S
CH


264
F2HC
F2HC
H
S(O)CH2CH3
N
N
S
CH


265
F2HC
F2HC
SCH3
H
N
N
S
N


266
F2HC
F2HC
S(O)CH3
H
N
N
S
N


267
F2HC
F2HC
SO2CH3
H
N
N
S
N


268
F2HC
F2HC
S(O)(NH)CH3
H
N
N
S
N


269
F2HC
F2HC
SO2N(H)CH3
H
N
N
S
N


270
F2HC
F2HC
S(O)CH2CH3
H
N
N
S
N


271
F2HC
F2HC
H
SCH3
N
N
S
N


272
F2HC
F2HC
H
S(O)CH3
N
N
S
N


273
F2HC
F2HC
H
SO2CH3
N
N
S
N


274
F2HC
F2HC
H
S(O)(NH)CH3
N
N
S
N


275
F2HC
F2HC
H
SO2N(H)CH3
N
N
S
N


276
F2HC
F2HC
H
S(O)CH2CH3
N
N
S
N


277
F2HC
F2HC
SCH3
H
N
N
O
CH


278
F2HC
F2HC
S(O)CH3
H
N
N
O
CH


279
F2HC
F2HC
SO2CH3
H
N
N
O
CH


280
F2HC
F2HC
S(O)(NH)CH3
H
N
N
O
CH


281
F2HC
F2HC
SO2N(H)CH3
H
N
N
O
CH


282
F2HC
F2HC
S(O)CH2CH3
H
N
N
O
CH


283
F2HC
F2HC
H
SCH3
N
N
O
CH


284
F2HC
F2HC
H
S(O)CH3
N
N
O
CH


285
F2HC
F2HC
H
SO2CH3
N
N
O
CH


286
F2HC
F2HC
H
S(O)(NH)CH3
N
N
O
CH


287
F2HC
F2HC
H
SO2N(H)CH3
N
N
O
CH


288
F2HC
F2HC
H
S(O)CH2CH3
N
N
O
CH


289
F3C
F3C
SCH3
H
CH
N
S
CH


290
F3C
F3C
S(O)CH3
H
CH
N
S
CH


291
F3C
F3C
SO2CH3
H
CH
N
S
CH


292
F3C
F3C
S(O)(NH)CH3
H
CH
N
S
CH


293
F3C
F3C
SO2N(H)CH3
H
CH
N
S
CH


294
F3C
F3C
S(O)CH2CH3
H
CH
N
S
CH


295
F3C
F3C
H
SCH3
CH
N
S
CH


296
F3C
F3C
H
S(O)CH3
CH
N
S
CH


297
F3C
F3C
H
SO2CH3
CH
N
S
CH


298
F3C
F3C
H
S(O)(NH)CH3
CH
N
S
CH


299
F3C
F3C
H
SO2N(H)CH3
CH
N
S
CH


300
F3C
F3C
H
S(O)CH2CH3
CH
N
S
CH


301
F3C
F3C
SCH3
H
CH
N
S
N


302
F3C
F3C
S(O)CH3
H
CH
N
S
N


303
F3C
F3C
SO2CH3
H
CH
N
S
N


304
F3C
F3C
S(O)(NH)CH3
H
CH
N
S
N


305
F3C
F3C
SO2N(H)CH3
H
CH
N
S
N


306
F3C
F3C
S(O)CH2CH3
H
CH
N
S
N


307
F3C
F3C
H
SCH3
CH
N
S
N


308
F3C
F3C
H
S(O)CH3
CH
N
S
N


309
F3C
F3C
H
SO2CH3
CH
N
S
N


310
F3C
F3C
H
S(O)(NH)CH3
CH
N
S
N


311
F3C
F3C
H
SO2N(H)CH3
CH
N
S
N


312
F3C
F3C
H
S(O)CH2CH3
CH
N
S
N


313
F3C
F3C
SCH3
H
CH
N
O
CH


314
F3C
F3C
S(O)CH3
H
CH
N
O
CH


315
F3C
F3C
SO2CH3
H
CH
N
O
CH


316
F3C
F3C
S(O)(NH)CH3
H
CH
N
O
CH


317
F3C
F3C
SO2N(H)CH3
H
CH
N
O
CH


318
F3C
F3C
S(O)CH2CH3
H
CH
N
O
CH


319
F3C
F3C
H
SCH3
CH
N
O
CH


320
F3C
F3C
H
S(O)CH3
CH
N
O
CH


321
F3C
F3C
H
SO2CH3
CH
N
O
CH


322
F3C
F3C
H
S(O)(NH)CH3
CH
N
O
CH


323
F3C
F3C
H
SO2N(H)CH3
CH
N
O
CH


324
F3C
F3C
H
S(O)CH2CH3
CH
N
O
CH


325
F3C
F3C
SCH3
H
N
N
S
CH


326
F3C
F3C
S(O)CH3
H
N
N
S
CH


327
F3C
F3C
SO2CH3
H
N
N
S
CH


328
F3C
F3C
S(O)(NH)CH3
H
N
N
S
CH


329
F3C
F3C
SO2N(H)CH3
H
N
N
S
CH


330
F3C
F3C
S(O)CH2CH3
H
N
N
S
CH


331
F3C
F3C
H
SCH3
N
N
S
CH


332
F3C
F3C
H
S(O)CH3
N
N
S
CH


333
F3C
F3C
H
SO2CH3
N
N
S
CH


334
F3C
F3C
H
S(O)(NH)CH3
N
N
S
CH


335
F3C
F3C
H
SO2N(H)CH3
N
N
S
CH


336
F3C
F3C
H
S(O)CH2CH3
N
N
S
CH


337
F3C
F3C
SCH3
H
N
N
S
N


338
F3C
F3C
S(O)CH3
H
N
N
S
N


339
F3C
F3C
SO2CH3
H
N
N
S
N


340
F3C
F3C
S(O)(NH)CH3
H
N
N
S
N


341
F3C
F3C
SO2N(H)CH3
H
N
N
S
N


342
F3C
F3C
S(O)CH2CH3
H
N
N
S
N


343
F3C
F3C
H
SCH3
N
N
S
N


344
F3C
F3C
H
S(O)CH3
N
N
S
N


345
F3C
F3C
H
SO2CH3
N
N
S
N


346
F3C
F3C
H
S(O)(NH)CH3
N
N
S
N


347
F3C
F3C
H
SO2N(H)CH3
N
N
S
N


348
F3C
F3C
H
S(O)CH2CH3
N
N
S
N


349
F3C
F3C
SCH3
H
N
N
O
CH


350
F3C
F3C
S(O)CH3
H
N
N
O
CH


351
F3C
F3C
SO2CH3
H
N
N
O
CH


352
F3C
F3C
S(O)(NH)CH3
H
N
N
O
CH


353
F3C
F3C
SO2N(H)CH3
H
N
N
O
CH


354
F3C
F3C
S(O)CH2CH3
H
N
N
O
CH


355
F3C
F3C
H
SCH3
N
N
O
CH


356
F3C
F3C
H
S(O)CH3
N
N
O
CH


357
F3C
F3C
H
SO2CH3
N
N
O
CH


358
F3C
F3C
H
S(O)(NH)CH3
N
N
O
CH


359
F3C
F3C
H
SO2N(H)CH3
N
N
O
CH


360
F3C
F3C
H
S(O)CH2CH3
N
N
O
CH










where


a) 360 compounds of formula (I.a):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


b) 360 compounds of formula (I.b):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


c) 360 compounds of formula (I.c):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


d) 360 compounds of formula (I.d):




embedded image


Wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


e) 360 compounds of formula (I.e):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


f) 360 compounds of formula (I.f):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


g) 360 compounds of formula (I.g):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


h) 360 compounds of formula (I.h):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


i) 360 compounds of formula (I.i):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


j) 360 compounds of formula (I.j):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


k) 360 compounds of formula (I.k):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


m) 360 compounds of formula (I.m):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


n) 360 compounds of formula (I.n):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


o) 360 compounds of formula (I.o):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


p) 360 compounds of formula (I.p):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


q) 360 compounds of formula (I.q):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


r) 360 compounds of formula (I.r):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


s) 360 compounds of formula (I.s):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


t) 360 compounds of formula (I.t):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


u) 360 compounds of formula (I.u):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


v) 360 compounds of formula (I.v):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


w) 360 compounds of formula (I.w):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


x) 360 compounds of formula (I.x):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


y) 360 compounds of formula (I.y):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


z) 360 compounds of formula (I.z):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


aa) 360 compounds of formula (I.aa):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ab) 360 compounds of formula (I.ab):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ac) 360 compounds of formula (I.ac):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ad) 360 compounds of formula (I.ad):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ae) 360 compounds of formula (I.ae):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


af) 360 compounds of formula (I.af):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ag) 360 compounds of formula (I.ag):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ah) 360 compounds of formula (I.ah):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ai) 360 compounds of formula (I.ai):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


aj) 360 compounds of formula (I.aj):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ak) 360 compounds of formula (I.ak):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


am) 360 compounds of formula (I.am):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


an) 360 compounds of formula (I.an):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ao) 360 compounds of formula (I.ao):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ap) 360 compounds of formula (I.ap):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


aq) 360 compounds of formula (I.aq):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ar) 360 compounds of formula (I.ar):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


as) 360 compounds of formula (I.as):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


at) 360 compounds of formula (I.at):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


au) 360 compounds of formula (I.au):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


av) 360 compounds of formula (I.av):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


aw) 360 compounds of formula (I.aw):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ax) 360 compounds of formula (I.ax):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ay) 360 compounds of formula (I.ay):




embedded image


Wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


az) 360 compounds of formula (I.az):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


ba) 360 compounds of formula (I.ba):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


bb) 360 compounds of formula (I.bb):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


bc) 360 compounds of formula (I.bc):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


bd) 360 compounds of formula (I.bd):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


be) 360 compounds of formula (I.be):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.


bf) 360 compounds of formula (I.bf):




embedded image


wherein R1, R2, R3, R5, G2, T, Y1 and Y2 are as defined in Table 1.









TABLE 2







Melting point and LC/MS data for compounds of Table 1









Compound
Melting point



No.
(° C.)
LC/MS











I.az.007
Rt = 5 min; MS: m/z = 586.0 (M + 1)


I.az.008
Rt = 4.83 min; MS: m/z = 602.0 (M + 1)


I.az.009
Rt = 4.97 min; MS: m/z = 618.2 (M + 1)


I.az.223
Rt = 5.42 min; MS: m/z = 604.3 (M + 1)





LCMS condition






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:


Instrumentation

Mass Spectrometer: 6410 Triple Quadruple Mass Spectrometer from Agilent Technologies


HPLC: Agilent 1200 Series HPLC


Optimized Mass Parameter

Ionisation method: Electrospray (ESI)


Polarity: positive and Negative Polarity Switch


Scan Type: MS2 Scan


Capillary (kV): 4.00


Fragmentor (V): 100.00


Gas Temperature (° C.): 350


Gas Flow (L/min): 11


Nebulizer Gas (psi): 35


Mass range: 110 to 1000 Da


DAD Wavelength range (nm): 190 to 400


Optimized Chromatographic Parameter

radient conditions (Solvent A: Water, 0.1% formic acid and Solvent B: Acetonitrile, 0.1% formic acid)


















Time (minutes)
A (%)
B (%)
Flow rate (ml/min)





















0
90
10
1.8



2.0
0
100
1.8



3.0
0
100
1.8



3.2
90
10
1.8



4.0
90
10
1.8










Column: Waters Xterra MS C18


Column length: 30 mm


Internal diameter of column: 4.6 mm


Particle Size: 3.5μ


Temperature: Room Temperature


The compounds according to the present invention can be prepared according to the above-mentioned reaction schemes, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).


BIOLOGICAL EXAMPLES

Phytophthora infestans/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.az.007, I.az.008, I.az.009, I.az.223 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.



Phytophthora infestans/Potato/Preventative (Potato Late Blight)

2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 2 days after application. The inoculated test plants are incubated at 18° C. with 14 h light/day and 100% rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (5-7 days after application).


Compounds I.az.007, I.az.223 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.



Phytophthora infestans/Potato/Curative (Potato Late Blight)

2-week old potato plants cv. Bintje are inoculated by spraying them with a sporangia suspension one day before application. The inoculated plants are sprayed in a spray chamber with the formulated test compound diluted in water. The inoculated test plants are incubated at 18° C. with 14 h light/day and 100% rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (3-4 days after application).


Compounds I.az.007, I.az.223 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.



Phytophthora infestans/Potato/Long Lasting (Potato Late Blight)

2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 6 days after application. The inoculated test plants are incubated at 18° C. with 14 h light/day and 100% rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (9-11 days after application).


Compounds I.az.007, I.az.223 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/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).


Compounds I.az.007, I.az.008, I.az.009, I.az.223 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/Grape/Preventative (Grape Downy Mildew)

5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying a sporangia suspension on their lower leaf surface one day after application. The inoculated test plants are incubated at 22° C. and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (6-8 days after application).


Compounds I.az.007, I.az.223 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/Grape/Curative (Grape Downy Mildew)

5-week-old grape seedlings cv. Gutedel are inoculated by spraying a sporangia suspension on their lower leaf surface one day before application. The inoculated grape plants are sprayed in a spray chamber with the formulated test compound diluted in water. The inoculated test plants are incubated at 22° C. and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (4-6 days after application).


Compounds I.az.223 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/Grape/Long Lasting (Grape Downy Mildew)

5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying a sporangia suspension on their lower leaf surface 6 days after application. The inoculated test plants are incubated at 22° C. and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (11-13 days after application).


Compounds I.az.007, I.az.223 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.



Pythium ultimum/Liquid Culture (Seedling Damping Off)

Mycelia fragments and oospores of a newly grown liquid culture of the fungus 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 mycelia/spore mixture is added. The test plates are incubated at 24° C. and the inhibition of growth is determined photometrically 2-3 days after application.


Compounds I.az.007, I.az.008, I.az.009, I.az.223 at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

Claims
  • 1. A compound of formula I:
  • 2. A compound according to claim 1, wherein one of R3 and R5 is C1-C4alkylsulfanyl, C3-C5cycloalkylsulfanyl, C1-C4haloalkysulfanyl, C1-C4alkylsulfinyl, C3-C5cycloalkylsulfinyl, C1-C4haloalkylsulfinyl, C1-C4alkylsulfonyl, C3-C5cycloalkylsulfonyl, C1-C4haloalkylsulfonyl and R4, R6, R7 and R8 are hydrogen.
  • 3. A compound according to claim 1, one of R3 and R5 is C1-C4alkylsulfanyl, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl and R4, R6, R7 and R8 are hydrogen.
  • 4. A compound according to claim 1, wherein the compound of formula I is a compound of formula I-a
  • 5. A compound according to claim 4, wherein Z is selected from Z-1, Z-4, Z-8, Z-10 and Z-12.
  • 6. A compound according to claim 4, wherein R14 and R15 are independently C1-C4alkyl, C1-C4haloalkyl or halogen.
  • 7. A compound according to claim 1, wherein R1 and R2 are independently methyl or halomethyl.
  • 8. A compound according to claim 1, wherein G1 is O and G2 is S.
  • 9. A compound according to claim 1, wherein p is 1 and n is 2.
  • 10. A compound of formula II
  • 11. A composition comprising at least one compound as defined in claim 1 and an agriculturally acceptable carrier, optionally comprising an adjuvant, and optionally comprising one or more additional pesticidally active compounds.
  • 12. A method of controlling or preventing an infestation of plants, propagation material thereof, harvested crops or of non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, which comprises the application of a compound as defined in claim 1, 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.
Priority Claims (1)
Number Date Country Kind
621/DEL/2012 Mar 2012 IN national
PCT Information
Filing Document Filing Date Country Kind
PCT/EP2013/053844 2/27/2013 WO 00