Microbiocidal tetrahydroisoquinoline derivatives

Abstract

Compounds of formula (I) wherein the substituents are as defined in claim 1, as well as agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, which can be used as fungicides. # imgabs0 #

Description

[0001] The present invention relates to microbicidal tetrahydroisoquinoline derivatives, for example as active ingredients, which have microbicidal activity, especially fungicidal activity. The invention also relates to the preparation of these tetrahydroisoquinoline derivatives, to intermediates useful in the preparation of these tetrahydroisoquinoline derivatives, to the preparation of these intermediates, to agrochemical compositions comprising at least one of these tetrahydroisoquinoline derivatives, to the preparation of these compositions and to the use of these tetrahydroisoquinoline derivatives or compositions in agriculture or horticulture for controlling or preventing the infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, especially fungi.

[0002] According to a first aspect of the invention, there is provided a compound of formula (I) or an agrochemically acceptable salt, stereoisomer or N-oxide thereof

[0003]

[0004] wherein

[0005] R 1 is selected from hydrogen, C1-C 4- alkyl, C2-C 4- alkenyl, C2-C4-alkynyl, or C3-C6-cycloalkyl;

[0006] R 2 is selected from hydrogen, halogen, C1-C 4- alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C 4- alkylcarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbimino, N-hydroxy-C-C1-C4-alkyl-carbimino, or C1-C 4- alkoxycarbonyl;

[0007] R 3 is selected from hydrogen, halogen, C1-C4-haloalkyl, or C1-C4-alkyl;

[0008] R 4 is selected from hydrogen, halogen, C1-C4-haloalkyl, C3-C6-cycloalkyl, or C1-C4-alkyl;

[0009] R 5 and R 6 are independently selected from hydrogen, or C1-C4-alkyl;

[0010] R 7 is selected from hydrogen, C1-C4-alkyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbimino, N-hydroxy-C-C1-C4- alkyl-carbonimino, C1-C4-alkoxycarbonyl, N-methoxy-N-methyl-carbonyl, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of said 5- or 6-membered heteroaryls contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, provided that not more than one is O or S; and wherein any one of said phenyl and 5- or 6-membered heteroaryls is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, carboxyl, C1-C4-alkyl, or C1-C4-alkoxy; and wherein said C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, C1-C4-alkyl, or C1-C4-alkoxy;

[0011] B 1 selected from CR 10 、or N;

[0012] B 2 selected from CR 11 、or N;

[0013] R 8 、R 9 、R 10 and R 11 are independently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-alkenyloxy, C2-C4-alkynyloxy, C1-C4-alkylthio, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, N-C1-C4-alkylamino, N,N-di(C1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, cyano-C1-C4-alkyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimino, N-hydroxy-C1-C4-alkyl-carbonimino, hydroxy, trifluoromethylsulfonyloxy, cyano, carboxyl, amino, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of said 5- or 6-membered heteroaryls contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, provided that not more than one is O or S; and wherein any one of said phenyl, 5- or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy;

[0014] A 1 、A2 and A 3 are independently selected from CR 12 , N, NR 13 , O or S, provided that A 1 , A 2 and A 3 at least one of which is selected from N, O or S, and A 1 , A 2 and A 3 no more than one of which is O or S;

[0015] R 12 , R 13 are independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, or C2-C4 alkynyl; and

[0016] Z 1 is selected from 6-membered heteroaryl containing 1 or 2 heteroatoms selected from N; wherein any one of said 6-membered heteroaryl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, cyano, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl.

[0017] Surprisingly, it has been found that, for practical purposes, the compounds of formula (I) have a very advantageous level of biological activity for protecting plants against diseases caused by fungi.

[0018] According to a second aspect of the present invention, there is provided an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I) according to the present invention. Such an agricultural composition may further comprise at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

[0019] According to a third aspect of the present invention, there is provided a method for controlling or preventing useful plants from being infested by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I) according to the present invention, or a composition comprising the compound of formula (I), is applied to these plants, parts thereof or their sites.

[0020] According to a fourth aspect of the present invention, there is provided the use of a compound of formula (I) according to the present invention as a fungicide. According to this particular aspect of the present invention, the use may exclude methods of treating the human or animal body by surgery or therapy and diagnostic methods practiced on the human or animal body.

[0021] According to a fifth aspect of the present invention, there is provided a compound of formula (IIb-1) as described separately in the present invention.

[0022] Compounds of formula (I) having at least one basic center can form, for example, acid addition salts with, for example: strong inorganic acids (such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acids), strong organic carboxylic acids (such as unsubstituted or halogen-substituted C1-C4 alkanoic acids, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid), or organic sulfonic acids (such as unsubstituted or halogen-substituted C1-C4 alkanesulfonic acids or arylsulfonic acids, for example methanesulfonic acid or p-toluenesulfonic acid). Compounds of formula (I) having at least one acidic group can form salts, for example, mineral salts, such as alkali metal or alkaline earth metal salts, for example sodium salts, potassium salts or magnesium salts; or salts with ammonia or organic amines (such as morpholine, piperidine, pyrrolidine, mono-, di- or tri-lower alkylamines, for example ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di- or tri-hydroxy-lower alkylamines, for example monoethanolamine, diethanolamine or triethanolamine).

[0023] In each case, the compounds of formula (I) according to the invention are in free form, oxidized form (such as N-oxides), or salt form (for example, in an agriculturally usable salt form).

[0024] N-oxides are the oxidized forms of tertiary amines or of nitrogen-containing heteroaromatic compounds. They are described, for example, in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.

[0025] The compounds of formula (I) according to the invention also include hydrates that may form during salt formation.

[0026] When substituents are represented as “optionally substituted”, this means that they may or may not carry one or more identical or different substituents, for example, one, two or three R xSubstituents. For example, C1-C6 alkyl groups substituted by 1, 2, or 3 halogens can include, but are not limited to, -CH2Cl, -CHCl2, -CCl3, -CH2F, -CHF2, -CF3, -CH2CF3, or -CF2CH3 groups. As another example, C1-C6 alkoxy groups substituted by 1, 2, or 3 halogens can include, but are not limited to, CH2ClO-, CHCl2O-, CCl3O-, CH2FO-, CHF2O-, CF3O-, CF3CH2O-, or CH3CF2O- groups. In addition, as used herein, the term "optionally substituted" can be used interchangeably with the term "unsubstituted or substituted".

[0027] As used herein, the term "halogen" or "halo group" refers to fluorine (fluorine / fluoro), chlorine (chlorine / chloro), bromine (bromine / bromo), or iodine (iodine / iodo), preferably fluorine, chlorine, or bromine. This also correspondingly applies to halogens in combination with other meanings, such as haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, and halocycloalkyl.

[0028] As used herein, amino means the -NH2 group.

[0029] As used herein, cyano means the -CN group.

[0030] As used herein, the term "hydroxyl" or "hydroxy" means the -OH group.

[0031] As used herein, the term "carboxylic acid" means the -COOH group.

[0032] As used herein, the term "C1-C n -alkyl" refers to a saturated straight-chain or branched hydrocarbon group having 1 to n carbon atoms and attached via any carbon atom, such as any of the following groups: methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl.

[0033] As used herein, the term "C2-C n"-enyl" means a straight or branched alkenyl chain moiety having from two to n carbon atoms and one or two double bonds, for example, vinyl, prop-1-enyl, but-2-enyl.

[0034] As used herein, the term "C2-C n -alkynyl" means a straight or branched alkynyl chain moiety having from two to n carbon atoms and a triple bond, for example, ethynyl, prop-2-ynyl, but-3-ynyl,

[0035] As used herein, the term "C3-C n -cycloalkyl" means a three (3)- to n-membered cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0036] As used herein, the term "C1-C n -alkoxy" means a straight or branched saturated alkyl (as mentioned above) having from one (1) to n carbon atoms attached via an oxygen atom, i.e., for example, any of the following groups: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, and 1,1-dimethylethoxy. As used herein, the term "C2-C n -alkenyloxy" means a straight or branched alkenyl chain (as mentioned above) having from two (2) to n carbon atoms attached via an oxygen atom.

[0037] As used herein, the term "C 2- C n -alkynyloxy" means a group having the formula -OR a wherein R a is C 2- C n -alkynyl as generally defined above.

[0038] As used herein, the term "C1-C n -alkoxy-C1-C n -alkyl" means an alkyl (as mentioned above) substituted by C1-C n -alkoxy. Examples are methoxymethyl, methoxyethyl, ethoxymethyl, and propoxymethyl.

[0039] As used herein, the term "C3-C n -cycloalkyl-C1-C n -alkyl" means an alkyl (as mentioned above) substituted by C3-C n -cycloalkyl. Examples are cyclopropylmethyl, cyclopropylethyl. Similarly, the term "C3-C n -halocycloalkyl-C1-C n"-alkyl" means an alkyl group substituted by a cycloalkyl group, wherein the cycloalkyl group is substituted by one or more identical or different halogen atoms. Examples are 3,3-difluorobutylmethyl and 1-chlorocyclopropylmethyl.

[0040] As used herein, the term "C1-C n -haloalkyl" means a straight-chain or branched-chain saturated alkyl group having 1 to n carbon atoms attached via any carbon atom (as mentioned above), wherein some or all of the hydrogen atoms in these groups may be replaced by fluorine, chlorine, bromine, and / or iodine, i.e., for example, any of the following: chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, or nonafluorobutyl. Accordingly, the term "C1-C2 fluoroalkyl" will mean a C1-C2 alkyl group bearing 1, 2, 3, 4, or 5 fluorine atoms, such as any of the following: difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, or pentafluoroethyl. Similarly, as used herein, the terms "C2-C n -haloalkenyl" or "C2-C n -haloalkynyl" mean a C2-C n -alkenyl or C2-C n -alkynyl substituted by one or more halogen atoms which may be the same or different. Similarly, as used herein, the terms "C3-C n -halocycloalkyl" or "C1-C n -haloalkoxy" mean a C3-C n -cycloalkyl or C1-C n -alkoxy substituted by one or more halogen atoms which may be the same or different.

[0041] As used herein, the term "cyano-C1-C n -alkyl" means a C1-C n-alkyl (as mentioned above), in which one of the hydrogen atoms in the group is replaced by a cyano group: for example, cyano-methyl, 2-cyano-ethyl, 2-cyano-propyl, 3-cyano-propyl, 1-(cyano-methyl)-2-ethyl, 1-(methyl)-2-cyano-ethyl, 4-cyanobutyl, etc. Similarly, the term "cyano-C3-C n -cycloalkyl" refers to C3-C n -cycloalkyl in which one of the hydrogen atoms is replaced by a cyano group; and the term "cyano-C3-C n -cycloalkyl-C1-C n -alkyl" refers to C1-C n -alkyl having cyano-C3-C n -cycloalkyl.

[0042] As used herein, the term "C1-C n -alkylthio" or "C1-C n -alkenylthio" refers to C1-C n -alkyl linked through a sulfur atom.

[0043] As used herein, the term "C1-C n -haloalkylthio" or "C1-C n -haloalkylthio" refers to C1-C n haloalkyl linked through a sulfur atom.

[0044] As used herein, the term "C1-C n -alkylsulfinyl" refers to C1-C n -alkyl linked through the sulfur atom of a sulfinyl (or S(=O)-) group.

[0045] As used herein, the term "C1-C n -alkylsulfonyl" refers to C1-C n -alkyl linked through the sulfur atom of a sulfonyl (or S(=O)2-) group.

[0046] As used herein, the term "C1-C n -alkylsulfonyl-C1-C n -alkyl" refers to C1-C n -alkyl substituted by C1-C n -alkylsulfonyl.

[0047] As used herein, the term "C1-C n -alkylcarbonyl" refers to C1-C n -alkyl linked through the carbon atom of a carbonyl (C=O) group.

[0048] As used herein, the term "C1-C n"-alkoxycarbonyl" means a C1-C n -alkoxy moiety attached through the carbon atom of a carbonyl (or C=O) group.

[0049] As used herein, the term "C1-C n -alkoxycarbonyl-C1-C n -alkyl" means a C1-C n -alkyl substituted with "C1-C n -alkoxycarbonyl.

[0050] As used herein, the term "benzoyl" means a phenyl group attached through the carbon atom of a carbonyl (C=O) group.

[0051] As used herein, the term "C1-C n -haloalkoxycarbonyl" means a C1-C n -haloalkoxy attached through the carbon atom of a carbonyl (C=O) group.

[0052] As used herein, the term "C2-C n -alkenyloxycarbonyl" means a C2-C n -alkenyloxy attached through the carbon atom of a carbonyl (C=O) group.

[0053] As used herein, the term "C1-C n -alkylaminocarbonyl" means a group of the formula R a NHC(=O)- as generally defined above, where R a is a C1-C n -alkyl.

[0054] As used herein, the term "di(C1-C n alkyl)aminocarbonyl" means a group of the formula R a NR b C(=O), where R a is a C 1- C n alkyl as generally defined above, and R b is a C 1- C n alkyl as generally defined above and attached through the carbon atom of a carbonyl (C=O) group.

[0055] As used herein, the term "N-C1-C n alkylamino" means a group of the formula -NH-R a where R a is a C1-C n alkyl as defined above.

[0056] As used herein, the term "N,N-di(C1-C n -alkyl)amino" refers to a group having the formula -N(R a )R a , wherein each R a is a C1-C n -alkyl which may be the same or different as defined above.

[0057] As used herein, the term "C1-C n -alkylcarbonyloxy-C1-C n -alkyl" refers to a C1-C n -alkyl substituted by a C1-C a -alkylcarbonyloxy (or R n C(=O)O-) group, wherein R a is a C1-C n -haloalkyl.

[0058] As used herein, the term "C1-C n -alkoxycarbonyloxy-C1-C n -alkyl" refers to a C1-C n -alkyl substituted by a C1-C c -alkoxycarbonyloxy (or R n C(=O)O-) group, wherein R c is a C1-C n -alkoxy. The C1-C n -alkoxy attached to the nitrogen may be substituted.

[0059] As used herein, the term "N-C1-C4 alkoxy-C-C1-C4 alkyl-carbonimino" refers to a group having the formula -C(R a )=NO(R b ), wherein R a is a C 1- C4 alkyl as generally defined above, and R b is a C 1- C4 alkyl as generally defined above.

[0060] As used herein, the term "N-hydroxy-C-C1-C4 alkyl-carbonimino" refers to a group having the formula -C(R a )=NOH, wherein R a is a C1-C4 alkyl as generally defined above.

[0061] As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic group containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S. Examples of heteroaryl include, but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, or pyridyl. The term "heteroaryl-C1-C n -alkyl" or "heteroaryl-C3-C n -cycloalkyl" refers to a C1-C n -alkyl or a C3-C n -cycloalkyl substituted by heteroaryl, respectively. Heteroaryl-C1-C n -alkyl or heteroaryl-C3-C n -cycloalkyl may be optionally substituted on the heteroaryl, alkyl, and / or cycloalkyl.

[0062] As used herein, the term "control" means reducing the number of pests, eliminating pests, and / or preventing further pest damage, such that damage to the plant or to plant-derived products is reduced.

[0063] As used herein, the term "pest" refers to insects and mollusks present in agriculture, horticulture, forestry, and the storage of plant-derived products (such as fruits, grains, and wood); and those pests associated with damage to man-made structures. The term pest encompasses all stages of the life cycle of the said pests.

[0064] As used herein, the term "effective amount" means the amount of a compound or its salt that provides the desired effect upon single or multiple applications.

[0065] The effective amount can be readily determined by those skilled in the art using known techniques and by observing the results obtained in similar situations. In determining the effective amount, many factors are considered, including but not limited to the type of plant or derived product to be treated; the pest to be controlled and its life cycle; the specific compound to be applied; the type of application; and other relevant circumstances.

[0066] As used herein, the term "room temperature" or "RT" or "rt" or "ambient temperature" refers to a temperature of about 15°C to about 35°C. For example, rt can refer to a temperature of about 20°C to about 30°C.

[0067] The following list provides substituents R for the compounds of formula (I) according to the present invention 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R8 , R 9 , B 1 , B 2 , A 1 , A 2 , A 3 and Z 1 definitions, including preferred definitions. For any one of these substituents, any of the definitions given below can be combined with any of the definitions of any other substituent given below or elsewhere in this document.

[0068] In one embodiment of the present invention, R 1 is selected from hydrogen, C1-C 4- alkyl, C2-C 4- alkenyl, C2-C4-alkynyl, or C3-C6 cycloalkyl. In another embodiment of the present invention, R 1 is C1-C4 alkyl. Preferably, R 1 is methyl, ethyl or isopropyl. More preferably, R 1 is methyl.

[0069] In one embodiment of the present invention, R 2 is selected from hydrogen, halogen, C1-C 4- alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, C1-C 4- alkylcarbonyl, N-C1-C4 alkoxy-C-C1-C4 alkyl-carbimino, N-hydroxy-C-C1-C4 alkyl-carbimino, or C1-C 4- alkoxycarbonyl. In another embodiment of the present invention, R 2 is hydrogen, halogen, C1-C4-alkyl, C3-C6 cycloalkyl, C1-C4 alkylcarbonyl, N-C1-C4 alkoxy-C1-C4 alkyl-carbimino, or N-hydroxy-C1-C4 alkyl-carbimino. Preferably, R 2 is hydrogen, halogen, methyl, ethyl, cyclopropyl, C1-C2 alkylcarbonyl, N-C1-C2 alkoxy-C1-C2 alkyl-carbimino, or N-hydroxy-C1-C2 alkyl-carbimino. More preferably, R 2 is hydrogen, fluorine, chlorine, bromine, methyl, ethyl, cyclopropyl, acetyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, or -C(CH3)=NOH. In a preferred embodiment of the present invention, R 2 is hydrogen, halogen, or C1-C4 alkyl. Most preferably, R 2 is hydrogen, chlorine, or methyl. In one preferred embodiment, R 2 is hydrogen. In another preferred embodiment, R 2is methyl. In yet another preferred embodiment, R 2 is chlorine.

[0070] In one embodiment, R 3 is selected from hydrogen, halogen, C1-C4 haloalkyl, or C1-C4 alkyl. Preferably, R 3 is hydrogen or C1-C4 alkyl. More preferably, R 3 is hydrogen or methyl. Most preferably, R 3 is hydrogen.

[0071] In one embodiment of the present invention, R 4 is selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6-cycloalkyl. Preferably, R 4 is hydrogen, chlorine, bromine, fluorine, methyl, ethyl, trifluoromethyl, difluoromethyl, or cyclopropyl. More preferably, R 4 is hydrogen, chlorine, bromine, or methyl. Even more preferably, R 4 is hydrogen or methyl. Most preferably, R 4 is hydrogen. In one embodiment of the present invention, R 4 is hydrogen. In another embodiment of the present invention, R 4 is methyl.

[0072] In one embodiment of the present invention, R 5 and R 6 are independently selected from hydrogen or C1-C4-alkyl. Preferably, R 5 and R 6 are independently selected from hydrogen, methyl, or ethyl. More preferably, R 5 and R 6 are independently selected from hydrogen or methyl. Even more preferably, R 5 and R 6 are hydrogen.

[0073] In one embodiment, R 7 is selected from hydrogen, C1-C4 alkyl, C1-C4-alkylcarbonyl, N-C1-C4 alkoxy-C-C1-C4 alkyl-carbodiimide, N-hydroxy-C-C1-C 4-alkyl-carbonimino, C1-C4-alkoxycarbonyl, N-methoxy-N-methyl-carbonyl, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, phenyl, a 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryls contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, provided that no more than one is O or S; and wherein any one of the phenyl and the 5- or 6-membered heteroaryl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, carboxyl, C1-C4-alkyl, or C1-C4-alkoxy; and wherein the C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, C1-C4-alkyl, or C1-C4-alkoxy.

[0074] In another embodiment of the present invention, R 7 is selected from hydrogen, C1-C4-alkyl, C3-C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbonimino, N-hydroxy-C-C1-C4-alkyl-carbonimino, N-methoxy-N-methyl-carbonyl, C1-C4-alkylaminocarbonyl, di(C1-C4-alkyl)aminocarbonyl, phenyl, a 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryls contains 1 heteroatom selected from N; and wherein any one of the phenyl and the 5- or 6-membered heteroaryl is unsubstituted or substituted by 1 or 2 substituents independently selected from halogen, C1-C4-haloalkyl, cyano, or C1-C4-alkyl; and wherein the C3-C6-cycloalkyl is unsubstituted or substituted by 1 substituent selected from cyano. Preferably, R 7 is selected from hydrogen, methyl, acetyl, C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, methoxycarbonyl, ethoxycarbonyl, N-methoxy-N-methyl-carbonyl, methylaminocarbonyl, dimethylaminocarbonyl, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], 3-cyanopyrazol-1-yl, 4-cyanopyrazol-1-yl, 5-chloropyrazol-1-yl, 5-fluoropyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, 5-methylpyrazol-1-yl, pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. More preferably, R 7 is selected from hydrogen, methyl, acetyl, C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, phenyl, 4-cyanophenyl, pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. Even more preferably, R7 Selected from hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl.

[0075] In another embodiment, R 7 is selected from hydrogen, C1-C4 alkyl, or C3-C6-cycloalkyl. Preferably, R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl. Even more preferably, R 7 is hydrogen, methyl, or cyclopropyl.

[0076] In another preferred embodiment, R 7 is C1-C4 alkyl. Preferably, R 7 is methyl or ethyl. More preferably, R 7 is methyl.

[0077] In one embodiment of the present invention, R 8 , R 9 , R 10 and R 11 are independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy-C1-C4 alkyl, N-C1-C4 alkylamino, N,N-diC1-C4 alkylamino, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyl, C1-C4 alkylaminocarbonyl, di(C1-C4)alkylaminocarbonyl, cyano-C1-C4 alkyl, N-C1-C4 alkoxy-C1-C4 alkyl-carbodiimide, N-hydroxy-C1-C4 alkyl-carbodiimide, hydroxy, trifluoromethylsulfonyloxy, cyano, carboxy, amino, phenyl, 5- or 6-membered heteroaryl, or C3-C6 cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, provided that not more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;

[0078] In one embodiment of the present invention, R 8 and R 9 are independently selected from hydrogen, halogen, cyano, C1-C4 alkyl, or C1-C4 alkoxy. Preferably, R 8 and R 9 are independently selected from hydrogen, halogen, methyl, methoxy, or cyano. More preferably, R 8 and R 9Independently selected from hydrogen, methyl, chlorine, fluorine, bromine, or methoxy. Even more preferably, R 8 and R 9 are independently selected from hydrogen or methoxy.

[0079] In another embodiment of the present invention, R 8 is hydrogen, halogen, or cyano. Preferably, R8 is hydrogen, bromine, chlorine, or cyano. More preferably, R 8 is hydrogen, cyano or bromine. Even more preferably, R 8 is hydrogen.

[0080] In one embodiment, R 9 is selected from hydrogen, halogen, C1-C3 alkyl, C1-C2 haloalkyl, C1-C3 haloalkoxy, C1-C4 alkoxy, C1-C3 alkenyloxy, C1-C3 alkynyloxy, C1-C2 alkylthio, C1-C2 alkylsulfinyl, C1-C2 alkylsulfonyl, C1-C2 alkoxy-C1-C2 alkyl, C1-C3 alkoxycarbonyl, C1-C2 alkylcarbonyl, C1-C2 alkylaminocarbonyl, bis(C1-C2 alkyl)aminocarbonyl, cyano-C1-C2 alkyl, N-C1-C2 alkoxy-C-C1-C2 alkyl-carbodiimide, N-hydroxy-C-C1-C2 alkyl-carbodiimide, hydroxy, trifluoromethylsulfonyloxy, cyano, carboxy, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], 3-cyanopyrazol-1-yl, 4-cyanopyrazol-1-yl, 5-chloropyrazol-1-yl, 4-chloropyrazol-1-yl, 3-chloropyrazol-1-yl, 5-fluoropyrazol-1-yl, 4-fluoropyrazol-1-yl, 3-fluoropyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, 5-methylpyrazol-1-yl, 4-methylpyrazol-1-yl, 3-methylpyrazol-1-yl, pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. Preferably, R 9is hydrogen, chlorine, fluorine, bromine, methyl, ethyl, trifluoromethyl, difluoromethyl, difluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, methoxy, ethoxy, propoxy, allyloxy, prop-2-ynyloxy, methylthio, methylsulfinyl, methylsulfonyl, methoxymethyl, ethoxymethyl, 2-methoxyethoxymethyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, acetyl, propionyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, methylaminocarbonyl, bis(methylamino)carbonyl, trifluoromethylsulfonyloxy, cyano, carboxy, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], 3-cyanopyrazol-1-yl, 4-cyanopyrazol-1-yl, 5-chloropyrazol-1-yl, 4-chloropyrazol-1-yl, 3-chloropyrazol-1-yl, 5-fluoropyrazol-1-yl, 4-fluoropyrazol-1-yl, 3-fluoropyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, 5-methylpyrazol-1-yl, 4-methylpyrazol-1-yl, 3-methylpyrazol-1-yl, pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. More preferably, R 9 is hydrogen, chlorine, bromine, fluorine, cyano, methyl, methoxy, propoxy, allyloxy, methoxymethyl, 2-methoxyethoxymethyl, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], 3-cyanopyrazol-1-yl, 4-cyanopyrazol-1-yl, 5-chloropyrazol-1-yl, 4-chloropyrazol-1-yl, 3-chloropyrazol-1-yl, 5-fluoropyrazol-1-yl, 4-fluoropyrazol-1-yl, 3-fluoropyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, 5-methylpyrazol-1-yl, 4-methylpyrazol-1-yl, 3-methylpyrazol-1-yl, pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. Even more preferably, R 9 is hydrogen, chlorine, bromine, cyano, methyl, or methoxy. Most preferably, R 9 is hydrogen or methoxy.

[0081] In an embodiment of the present invention, B 1 is CR 10 and B 2 is CR 11 , or B 1 is N and B 2 is CR 11 , or B 1 is CR 10 and B 2 is N. Preferably, B1 is CR 10 and B 2 is CR 11 。

[0082] In one embodiment of the present invention, R 10 and R 11 are independently selected from hydrogen, halogen, hydroxy, cyano, amino, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy-C1-C4 alkyl, N-C1-C4 alkylamino, N,N-diC1-C4 alkylamino, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyl, C1-C2 alkylaminocarbonyl, bis(C1-C2 alkyl)aminocarbonyl, cyano-C1-C4 alkyl, N-C1-C4 alkoxy-C1-C4 alkyl-carbodiimide, N-hydroxy-C1-C4 alkyl-carbodiimide, alkyl-C═N-OR X (X = (CH2)n-CN, hydroxy, trifluoromethylsulfonyloxy, carboxy, phenyl, a 5- or 6-membered heteroaryl, or a C3-C6 cycloalkyl; wherein any one of the 5- or 6-membered heteroaryls contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy. Preferably, R 10 and R 11Independently selected from hydrogen, chlorine, fluorine, bromine, methyl, ethyl, trifluoromethyl, difluoromethyl, difluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, methoxy, ethoxy, propoxy, allyloxy, prop-2-ynyloxy, methylthio, methylsulfinyl, methylsulfonyl, methoxymethyl, ethoxymethyl, 2-methoxyethoxymethyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, acetyl, propionyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, methylaminocarbonyl, bis(methylamino)carbonyl, trifluoromethylsulfonyloxy, cyano, carboxy, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], 3-cyanopyrazol-1-yl, 4-cyanopyrazol-1-yl, 5-chloropyrazol-1-yl, 4-chloropyrazol-1-yl, 3-chloropyrazol-1-yl, 5-fluoropyrazol-1-yl, 4-fluoropyrazol-1-yl, 3-fluoropyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, 5-methylpyrazol-1-yl, 4-methylpyrazol-1-yl, 3-methylpyrazol-1-yl, pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. More preferably, R 10 and R 11 Independently selected from hydrogen, chlorine, bromine, fluorine, cyano, methyl, methoxy, propoxy, allyloxy, methoxymethyl, 2-methoxyethoxymethyl, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, [4-(trifluoromethyl)pyrazol-1-yl], [3-(trifluoromethyl)pyrazol-1-yl], 3-cyanopyrazol-1-yl, 4-cyanopyrazol-1-yl, 5-chloropyrazol-1-yl, 4-chloropyrazol-1-yl, 3-chloropyrazol-1-yl, 5-fluoropyrazol-1-yl, 4-fluoropyrazol-1-yl, 3-fluoropyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, 5-methylpyrazol-1-yl, 4-methylpyrazol-1-yl, 3-methylpyrazol-1-yl, pyrazol-1-yl, C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, cyclopropyl, or 1-cyanocyclopropyl. Even more preferably, R 10 and R 11 Independently selected from hydrogen, chlorine, bromine, or cyano.

[0083] In another embodiment, R 10 and R 11 Independently selected from hydrogen, halogen, C1-C3 alkyl, or C1-C3 alkoxy. Preferably, R 10 and R 11 Independently selected from hydrogen or halogen. More preferably, R 10 and R11 is hydrogen, bromine, or chlorine. Even more preferably, R 10 and R 11 are hydrogen.

[0084] In one embodiment of the present invention, A 1 , A 2 and A 3 are independently selected from CR 12 , N, NR 13 , O or S, provided that at least one of A 1 , A 2 and A 3 is selected from N, O or S, and no more than one of A 1 , A 2 and A 3 is O or S. In another embodiment of the present invention, A 1 and A 2 are independently selected from CR 12 , N or O, and A 3 is CR 12 , N, O or S, provided that at least one of A 1 , A 2 and A 3 is selected from N, O or S, and no more than one of A 1 , A 2 and A 3 is O or S. Preferably, A 1 and A 2 are independently selected from N or O; and A 3 is CR 12 , O or S, provided that at least one of A 1 , A 2 and A 3 is N or O, and no more than one of A 1 , A 2 and A 3 is O.

[0085] In an embodiment of the present invention, R 12 is hydrogen or a C1-C4 alkyl group. Preferably, R 12 is hydrogen or methyl. More preferably, R 12 is hydrogen.

[0086] In an embodiment of the present invention, R 13 is hydrogen or a C1-C4 alkyl group. Preferably, R 13 is hydrogen or methyl. More preferably, R 13 is hydrogen.

[0087] In one embodiment of the present invention, Z 1Selected from 6-membered heteroaryl; wherein any one of said 6-membered heteroaryl contains 1 or 2 heteroatoms independently selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl. In one embodiment of the present invention, Z 1 Selected from 6-membered heteroaryl, wherein any one of said 6-membered heteroaryl contains 1 or 2 heteroatoms selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 alkoxy. Preferably, Z 1 Selected from 6-membered heteroaryl, wherein any one of said 6-membered heteroaryl contains 1 or 2 heteroatoms selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen or C1-C4 haloalkyl. More preferably, Z 1 Selected from 6-membered heteroaryl, wherein any one of said 6-membered heteroaryl contains 1 or 2 heteroatoms selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1 or 2 substituents selected from fluorine.

[0088] In another embodiment of the present invention, Z 1 Selected from 6-membered heteroaryl; wherein any one of said 6-membered heteroaryl contains 1 heteroatom selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 alkoxy. Preferably, Z 1 Selected from 6-membered heteroaryl, wherein any one of said 6-membered heteroaryl contains 1 heteroatom selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen or C1-C4 haloalkyl. More preferably, Z 1 Selected from 6-membered heteroaryl; wherein any one of said heteroaryl contains 1 heteroatom selected from N; and wherein any one of said 6-membered heteroaryl is unsubstituted or substituted with 1 or 2 substituents selected from fluorine.

[0089] In another embodiment, Z 1selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any one of the pyridyl-, pyrazin-, pyridazin-, or pyrimidin- moieties is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from halogen, C1-C4 haloalkyl, cyano, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl. Preferably, Z 1 selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any one of the pyridyl-, pyrazin-, pyridazin- or pyrimidin- moieties is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from halogen, C1-C4 haloalkyl, or C1-C4 alkyl. More preferably, Z 1 selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any one of the pyridyl-, pyrazin-, pyridazin- or pyrimidin- moieties is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from fluorine, trifluoromethyl, difluoromethyl, or methyl. More preferably, Z 1 selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any one of the pyridyl-, pyrazin-, pyridazin- or pyrimidin- moieties is unsubstituted or substituted with 1 or 2 substituents selected from fluorine.

[0090] In another more preferred embodiment of the present invention, Z 1Selected from 5-fluoropyrimidin-4-yl, 3,6-difluoro-2-pyridinyl, 4,6-difluoro-2-pyridinyl, 4,5-difluoro-2-pyridinyl, 5,6-difluoro-2-pyridinyl, 3-fluoropyridin-4-yl, 2-fluoropyridin-4-yl, 2,3-difluoropyridin-4-yl, 2,5-difluoropyridin-4-yl, 2,6-difluoropyridin-4-yl, 3,5-difluoropyridin-4-yl, 2,5-difluoropyridin-4-yl, 2-fluoropyridin-3-yl, 6-fluoropyridin-3-yl, 5-fluoropyridin-3-yl, 4-fluoropyridin-3-yl, 2,6-difluoropyridin-3-yl, 2,5-difluoropyridin-3-yl, 2,4-difluoropyridin-3-yl, 4,6-difluoropyridin-3-yl, 5,6-difluoropyridin-3-yl, 6-fluoropyrimidin-4-yl, 2-fluoropyrimidin-4-yl, 2,5-difluoropyrimidin-4-yl, 2,6-difluoropyrimidin-4-yl, 5,6-difluoropyrimidin-4-yl, 4-fluoropyrimidin-5-yl, 2-fluoropyrimidin-5-yl, 2,4-difluoropyrimidin-5-yl, 4-fluoropyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 4,5-difluoropyrimidin-2-yl, 4,6-difluoropyrimidin-2-yl, 4-fluoropyridazin-3-yl, 5-fluoropyridazin-3-yl, 6-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, 4,6-difluoropyridazin-3-yl, 5,6-difluoropyridazin-3-yl, 3-fluoropyridazin-4-yl, 6-fluoropyridazin-4-yl, 5-fluoropyridazin-4-yl, 3,6-difluoropyridazin-4-yl, 5,6-difluoropyridazin-4-yl, 3,5-difluoropyridazin-4-yl, 3,5-difluoro-2-pyridinyl, 3,4-difluoro-2-pyridinyl, 6-fluoro-2-pyridinyl, 4-fluoro-2-pyridinyl, 5-fluoro-2-pyridinyl, 3-fluoro-2-pyridinyl, 4,5-difluoropyridin-3-yl, or 4-fluoropyrimidin-5-yl. Preferably, Z 1 Selected from 3-fluoropyridin-2-yl, 5-fluoropyridin-2-yl, 6-fluoropyridin-2-yl, 3,4-difluoropyridin-2-yl, 3,5-difluoropyridin-2-yl, 2-fluoropyridin-4-yl, 5-fluoropyrimidin-4-yl, 5-fluoropyrimidin-2-yl, 4-fluoropyridazin-3-yl, 5-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl. More preferably, Z 1 Selected from 3-fluoropyridin-2-yl, 5-fluoropyridin-2-yl, 3,4-difluoropyridin-2-yl, 3,5-difluoropyridin-2-yl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl or 5-fluoropyridazin-4-yl. Most preferably, Z 1 Selected from 3-fluoropyridin-2-yl, 5-fluoropyridin-2-yl, 3,4-difluoropyridin-2-yl, or 3,5-difluoropyridin-2-yl.

[0091] Accordingly, the present invention provides compounds having the formula (I), which have R as defined above in all combinations / each permutation 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 、B 2 、A 1 、A 2 、A 3 and Z 1 。

[0092] Embodiments according to the present invention are provided, as listed below.

[0093] Preferably, in the compounds having the formula (I)

[0094] R 1 is methyl,

[0095] R 2 is hydrogen, chlorine, or methyl;

[0096] R 3 is hydrogen;

[0097] R 4 is hydrogen, or methyl;

[0098] R 5 and R 6 are hydrogen;

[0099] R 7 is hydrogen, C1-C4 alkyl, or C3-C6-cycloalkyl;

[0100] R 8 is hydrogen, bromine, chlorine, or cyano;

[0101] R 9 is hydrogen, bromine, chlorine, cyano, methyl, or methoxy;

[0102] B 1 is N or CR 10 wherein R 10 is hydrogen, bromine, chlorine, or cyano;

[0103] B 2 is N or CR 11 wherein R 11 is hydrogen, bromine, chlorine, or cyano; and

[0104] A 1 、A 2 、A3 and Z 1 is as defined for a compound of formula (I) according to the invention.

[0105] Preferably, in the compound of formula (I)

[0106] R 1 is methyl,

[0107] R 2 is hydrogen, chlorine, or methyl;

[0108] R 3 is hydrogen;

[0109] R 4 is hydrogen, or methyl;

[0110] R 5 and R 6 are hydrogen;

[0111] R 7 is hydrogen, C1-C4 alkyl, or C3-C6-cycloalkyl;

[0112] R 8 is hydrogen, bromine, chlorine, or cyano;

[0113] R 9 is hydrogen, bromine, chlorine, cyano, methyl, or methoxy;

[0114] B 1 is N or CR 10 , where R 10 is hydrogen, bromine, chlorine, or cyano;

[0115] B 2 is N or CR 11 , where R 11 is hydrogen, bromine, chlorine, or cyano;

[0116] Z 1 is 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any one of the pyridyl-, pyrazin-, pyridazin or pyrimidin- moieties is unsubstituted or substituted by 1 or 2 substituents selected from fluorine; and

[0117] A 1 、A 2 and A 3 is as defined for a compound of formula (I) according to the invention.

[0118] In one embodiment of the invention, the compound of formula (I) may be a compound of formula (I-A)

[0119]

[0120] wherein

[0121] R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 and B 2 and Z 1 are as defined for a compound of formula (I) according to the invention, and A is selected from A1 to A36:

[0122]

[0123] wherein indicates the bond to the C(=O) group and the arrow indicates the bond to the Z 1 group, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 、B 2 and Z 1 are as defined for a compound of formula (I) according to the invention, and R 12a 、R 13a 、R 14a 、R 12b 、R 13b and R 14b are independently selected from hydrogen, C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl.

[0124] In one embodiment of the invention, in a compound of formula (I-A), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 and B 2 and Z1 is as defined for a compound of formula (I) according to the present invention, and A is selected from

[0125]

[0126] wherein indicates a bond to the C(=O) group and the arrow indicates a bond to the Z 1 group, and R 12a 、R 13a and R 14a are independently selected from hydrogen or C1-C4 alkyl. Preferably, R 12a 、R 13a and R 14a are hydrogen.

[0127] In another embodiment of the present invention, in a compound of formula (I-A), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 and B 2 as well as Z 1 is as defined for a compound of formula (I) according to the present invention, and A is selected from

[0128]

[0129] wherein indicates a bond to the C(=O) group and the arrow indicates a bond to the Z 1 group, and R 12a 、R 13a and R 14a are independently selected from hydrogen or C1-C4 alkyl. Preferably, R 12a 、R 13a and R 14a are hydrogen.

[0130] In another embodiment of the present invention, in a compound of formula (I-A), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 and B 2 as well as Z 1is as defined for a compound of formula (I) according to the invention, and A is selected from

[0131]

[0132] wherein indicates the bond to the C(=O) group and the arrow indicates the bond to the Z 1 group, and R 14a is selected from hydrogen or C1-C4 alkyl. Preferably, R 14a is hydrogen.

[0133] In another embodiment of the invention, in a compound of formula (I-A), wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 and B 2 as well as Z 1 is as defined for a compound of formula (I) according to the invention, and A is selected from

[0134]

[0135] wherein indicates the bond to the C(=O) group and the arrow indicates the bond to the Z 1 group, and R 14a is selected from hydrogen or C1-C4 alkyl. Preferably, R 14a is hydrogen.

[0136] In one embodiment of the invention, R 12a 、R 13a 、R 14a 、R 12b 、R 13b and R 14b are independently selected from hydrogen or methyl.

[0137] In another embodiment of the invention, R 12a 、R 13a 、R 14a 、R 12b 、R 13b and R 14b are hydrogen.

[0138] In another embodiment of the invention, R 12a 、R 13a 、R 14a 、R 12b 、R13b and R 14b is methyl.

[0139] Preferably, in the compound of formula (I-A), A is selected from A4, A7 or A9, and R 14a is hydrogen.

[0140] In one embodiment of the present invention, the compound of formula (I-A) can be a compound of formula (I-A1), wherein R 1 is methyl, B 1 is CH, and A is as defined for the compound (I-A),

[0141]

[0142] wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , B 2 and Z 1 are as defined for the compound of formula (I) according to the present invention.

[0143] Preferably, the compound of formula (I-A1), wherein B 2 is N, and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and Z 1 are as defined for the compound of formula (I) according to the present invention.

[0144] Preferably, the compound of formula (I-A1), wherein B 2 is CR 11 , and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 and Z 1 are as defined for the compound of formula (I) according to the present invention.

[0145] In a variant of this embodiment of the present invention, the compound having formula (I-A) may be a compound having formula (I-A2), wherein B 1 is CH; R 1 is methyl, R 3 、R 5 and R 6 are hydrogen; and A is as defined for the compound (I-A); and

[0146]

[0147] wherein R 2 、R 4 、R 7 、R 8 、R 9 、B 2 and Z 1 are as defined for the compound having formula (I) according to the present invention.

[0148] Preferably, in the compound having formula (I-A2)

[0149] R 2 is hydrogen, methyl or chlorine;

[0150] R 4 is hydrogen or methyl;

[0151] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0152] R 8 is hydrogen, cyano, or bromine;

[0153] R 9 is hydrogen or methoxy;

[0154] B 2 is CR 11 ,wherein R 11 is hydrogen; and

[0155] A and Z 1 are as defined for the compound having formula (I) according to the present invention.

[0156] Preferably, in the compound having formula (I-A2)

[0157] R 2 is hydrogen, methyl, or chlorine;

[0158] R 4 is hydrogen or methyl;

[0159] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0160] R 8 is hydrogen, cyano, or bromo;

[0161] R 9 is hydrogen or methoxy;

[0162] B 2 is CR 11 wherein R 11 is hydrogen

[0163] A is A4, A7 or A9; and

[0164] Z 1 is as defined for the compounds of formula (I) according to the invention.

[0165] Preferably, in the compounds of formula (I-A2)

[0166] R 2 is hydrogen, methyl, or chloro;

[0167] R 4 is hydrogen or methyl;

[0168] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0169] R 8 is hydrogen, cyano, or bromo;

[0170] R 9 is hydrogen or methoxy;

[0171] B 2 is CR 11 wherein R 11 is hydrogen

[0172] A is A4, A7 or A9; and

[0173] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl.

[0174] In one embodiment of the invention, the compound of formula (I-A) can be a compound of formula (I-A3), wherein R 1 is methyl; B 1 and B 2 is CH; and A is as defined for compound (I-A), and

[0175]

[0176] wherein R2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and Z 1 are as defined for the compounds of formula (I) according to the invention.

[0177] In a variant of this embodiment of the invention, the compound of formula (I-A) can be a compound of formula (I-A4), where B 1 and B 2 are CH; R 1 is methyl; R 3 , R 4 , R 5 and R 6 are hydrogen, and A is as defined for the compound (I-A):

[0178]

[0179] where R 2 , R 7 , R 8 , R 9 and Z 1 are as defined for the compounds of formula (I) according to the invention.

[0180] Preferably, in the compound of formula (I-A4)

[0181] R 2 is hydrogen, methyl or chlorine;

[0182] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0183] R 8 is hydrogen, cyano, or bromine;

[0184] R 9 is hydrogen, or methoxy; and

[0185] A and Z 1 are as defined for the compounds of formula (I) according to the invention.

[0186] Preferably, in the compound of formula (I-A4)

[0187] R 2 is hydrogen, methyl, or chlorine;

[0188] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0189] R 8 is hydrogen, cyano, or bromo;

[0190] R 9 is hydrogen, or methoxy;

[0191] A is A4, A7, or A9; and

[0192] Z 1 is as defined for the compounds of formula (I) according to the invention.

[0193] More preferably, in the compounds of formula (I-A4)

[0194] R 2 is hydrogen, methyl, or chloro;

[0195] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0196] R 8 is hydrogen, cyano, or bromo;

[0197] R 9 is hydrogen, or methoxy;

[0198] A is A4, A7, or A9; and

[0199] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl.

[0200] Even more preferably, in the compounds of formula (I-A4)

[0201] R 2 is hydrogen, methyl, or chloro;

[0202] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0203] R 8 is hydrogen, cyano, or bromo;

[0204] R 9 is hydrogen, or methoxy;

[0205] A is A4, A7, or A9; and

[0206] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl.

[0207] In one embodiment of the present invention, the compound having the formula (I-A) can be a compound having the formula (I-A5), wherein R 1 is methyl; R 4 is methyl; R 3 、R 4 、R 5 and R 6 are hydrogen; B 1 and B 2 are CH; and A is as defined for the compound (I-A),

[0208] racemic cis-(I-A5)

[0209] and wherein R 2 、R 7 、R 8 、R 9 and Z 1 are as defined for the compound having the formula (I) according to the present invention, and wherein when R 7 is not hydrogen, the pyrazole-derivative-substituent and R 7 have a cis-relationship with each other in the stereochemistry at the carbon having "*".

[0210] Preferably, in the compound having the formula (I-A5)

[0211] R 2 is hydrogen, methyl, or chloro;

[0212] R 7 is methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0213] R 8 is hydrogen, cyano, or bromo;

[0214] R 9 is hydrogen, or methoxy; and

[0215] A and Z 1 are as defined for the compound having the formula (I) according to the present invention.

[0216] More preferably, in the compound having the formula (I-A5)

[0217] R 2 is hydrogen, methyl, or chloro;

[0218] R 7 is methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0219] R 8 is hydrogen, cyano, or bromo;

[0220] R 9 is hydrogen, or methoxy;

[0221] A is A4, A7, or A9; and

[0222] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl.

[0223] Even more preferably, in the compounds of formula (I-A5)

[0224] R 2 is hydrogen, methyl, or chlorine;

[0225] R 7 is methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0226] R 8 is hydrogen, cyano, or bromine;

[0227] R 9 is hydrogen, or methoxy;

[0228] A is A4, A7, or A9; and

[0229] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl.

[0230] In another embodiment of the present invention, the compound of formula (I-A) can be a compound of formula (I-B), wherein R 1 is methyl; R 3 , R 5 , R 6 are hydrogen; B 1 and B 2 are CH; and A is A4

[0231]

[0232] And wherein R 2 , R 4 , R 7 , R 8 , R 9 and Z 1 are as defined for the compounds of formula (I) according to the present invention.

[0233] Preferably, in the compounds of formula (I-B)

[0234] R 2 is hydrogen, methyl, or chlorine;

[0235] R 4 is hydrogen or methyl;

[0236] R 7 is hydrogen, methyl, cyclopropyl, or 1 - cyanocyclopropyl;

[0237] R 8 is hydrogen, cyano, or bromine;

[0238] R 9 is hydrogen or methoxy; and

[0239] Z 1 is as defined for the compounds of formula (I) according to the present invention.

[0240] More preferably, in the compounds of formula (I - B)

[0241] R 2 is hydrogen, methyl, or chlorine;

[0242] R 4 is hydrogen or methyl;

[0243] R 7 is hydrogen, methyl, cyclopropyl, or 1 - cyanocyclopropyl;

[0244] R 8 is hydrogen, cyano, or bromine;

[0245] R 9 is hydrogen or methoxy; and

[0246] Z 1 is 3 - fluoro - 2 - pyridyl, 5 - fluoro - 2 - pyridyl, 3,4 - difluoro - 2 - pyridyl, 3,5 - difluoro - 2 - pyridyl, 4 - fluoropyridazin - 3 - yl, 4,5 - difluoropyridazin - 3 - yl, or 5 - fluoropyridazin - 4 - yl.

[0247] Even more preferably, in the compounds of formula (I - B)

[0248] R 2 is hydrogen, methyl, or chlorine;

[0249] R 4 is hydrogen or methyl;

[0250] R 7 is hydrogen, methyl, cyclopropyl, or 1 - cyanocyclopropyl;

[0251] R 8 is hydrogen, cyano or bromine;

[0252] R 9is hydrogen or methoxy; and

[0253] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl or 3,5-difluoro-2-pyridyl.

[0254] Even more preferably, in the compounds of formula (I-B)

[0255] R 2 is hydrogen, methyl or chlorine;

[0256] R 4 is hydrogen;

[0257] R 7 is methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0258] R 8 is hydrogen, cyano, or bromine;

[0259] R 9 is hydrogen or methoxy; and

[0260] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl.

[0261] In another embodiment of the present invention, the compound of formula (I-A) can be a compound of formula (I-C), wherein R 1 is methyl; R 3 , R 5 , R 6 is hydrogen; B 1 and B 2 is CH; and A is A7

[0262]

[0263] And wherein R 2 , R 4 , R 7 , R 8 , R 9 and Z 1 is as defined for the compounds of formula (I) according to the present invention.

[0264] Preferably, in the compounds of formula (I-C)

[0265] R 2 is hydrogen, methyl, or chlorine;

[0266] R 4 is hydrogen or methyl;

[0267] R7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0268] R 8 is hydrogen, cyano, or bromo;

[0269] R 9 is hydrogen or methoxy; and

[0270] Z 1 is as defined for the compounds of formula (I) according to the invention.

[0271] More preferably, in the compounds of formula (I-C)

[0272] R 2 is hydrogen, methyl, or chloro;

[0273] R 4 is hydrogen or methyl;

[0274] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0275] R 8 is hydrogen, cyano, or bromo;

[0276] R 9 is hydrogen or methoxy; and

[0277] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl.

[0278] Even more preferably, in the compounds of formula (I-C)

[0279] R 2 is hydrogen, methyl, or chloro;

[0280] R 4 is hydrogen or methyl;

[0281] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0282] R 8 is hydrogen, cyano, or bromo;

[0283] R 9 is hydrogen or methoxy; and

[0284] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl.

[0285] In another embodiment of the present invention, the compound having the formula (I-A) may be a compound having the formula (I-D), wherein R 1 is methyl; R 3 , R 5 , R 6 are hydrogen; B 1 and B 2 are CH; and A is A9

[0286]

[0287] and wherein R 2 , R 4 , R 7 , R 8 , R 9 and Z 1 are as defined for the compound having the formula (I) according to the present invention.

[0288] Preferably, in the compound having the formula (I-D)

[0289] R 2 is hydrogen, methyl, or chlorine;

[0290] R 4 is hydrogen or methyl;

[0291] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0292] R 8 is hydrogen, cyano, or bromine;

[0293] R 9 is hydrogen or methoxy; and

[0294] Z 1 is as defined for the compound having the formula (I) according to the present invention.

[0295] More preferably, in the compound having the formula (I-D)

[0296] R 2 is hydrogen, methyl, or chlorine;

[0297] R 4 is hydrogen or methyl;

[0298] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0299] R 8 is hydrogen, cyano, or bromine;

[0300] R 9is hydrogen or methoxy; and

[0301] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 4-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl.

[0302] Even more preferably, in the compounds of formula (I-D)

[0303] R 2 is hydrogen, methyl, or chlorine;

[0304] R 4 is hydrogen or methyl;

[0305] R 7 is hydrogen, methyl, cyclopropyl, or 1-cyanocyclopropyl;

[0306] R 8 is hydrogen, cyano or bromine;

[0307] R 9 is hydrogen or methoxy; and

[0308] Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl.

[0309] The following intermediates are new and constitute another aspect of the present invention in themselves.

[0310] A compound of formula (IIb) or a salt thereof:

[0311]

[0312] wherein R 0 is C1-C6 alkyl, and wherein A 1 、A 2 、A 3 and Z 1 are as defined for the compounds of formula (I) according to the present invention.

[0313] The intermediate compound of formula (IIb) has the same definitions of A 1 、A 2 、A 3 and Z 1 as those of the compounds of formula (I) according to the present invention and their corresponding preferred cases.

[0314] In one embodiment, R 0 is C1-C4 alkyl; A 1 、A2 and 3 Z 1 are as defined for the compounds of formula (I) according to the present invention.

[0315] In one embodiment, a compound of formula (IIb) can be a compound of formula (IIb-1):

[0316]

[0317] wherein

[0318] Z 1 is as defined for the compounds of formula (I) according to the present invention; R 0 is as defined for the compounds of formula (IIb); and A is selected from A1 to A36 as defined above for the compounds of formula (I-A).

[0319] Preferably, in the compound of formula (IIb-1), A is selected from

[0320]

[0321] wherein indicates the bond to the C(=O) group and the arrow indicates the bond to the Z 1 group, and R 14a is selected from hydrogen or C1-C4 alkyl, wherein Z 1 is as defined for the compounds of formula (I) according to the present invention, and R 0 is as defined for the compounds of formula (IIb). Preferably, R 14a is hydrogen.

[0322] In another embodiment of the present invention, in the compound of formula (IIb-1), A is selected from

[0323]

[0324] wherein indicates the bond to the C(=O) group and the arrow indicates the bond to the Z 1 group, and R 14a is selected from hydrogen or C1-C4 alkyl, wherein Z 1 is as defined for the compounds of formula (I) according to the present invention, and R 0 is as defined for the compounds of formula (IIb). Preferably, R 14a is hydrogen.

[0325] In one embodiment, in the compound of formula (IIb-1), A is A4; Z 1is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl; and R 0 is as defined for the compounds of formula (IIb).

[0326] In one embodiment, in the compounds of formula (IIb-1), A is A7; Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, or 3,5-difluoro-2-pyridyl; and R 0 is as defined for the compounds of formula (IIb).

[0327] In one embodiment, in the compounds of formula (IIb-1), A is A9; Z 1 is 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl or 3,5-difluoro-2-pyridyl; R 14a is hydrogen, and R 0 is as defined for the compounds of formula (IIb).

[0328] In any one of the compounds selected from the compounds of formula (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-A5), (I-B), (I-C), or (I-D) according to the present invention or the compounds selected from the compounds listed in Tables A-1 to A-26 or the compounds listed in Table P (below), the presence of one or more possible asymmetric carbon atoms means that these compounds can exist in chiral isomer forms, i.e., enantiomeric or diastereomeric forms.

[0329] More preferably, the compounds of formula (I) according to the present invention are selected from the compounds listed in any one of Tables A-1 to A-26.

[0330] Even more preferably, the compounds of formula (I) according to the present invention are selected from the compounds listed in Table P (below).

[0331] In one embodiment, the compounds of formula (I) according to the present invention are selected from those listed in Table P (below)

[0332] [4-(1-Methylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-[5-(4-pyridyl)isoxazol-3-yl]methanone (P-1),

[0333] [4-(1-Methylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-[5-(3-pyridyl)isoxazol-3-yl]methanone (P-2),

[0334] [4-(1-Methylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-[5-(2-pyridyl)isoxazol-3-yl]methanone (P-3),

[0335] [5-(6-Methoxy-3-pyridyl)isoxazol-3-yl]-[4-(1-methylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (P-4),

[0336] [5-(2-Methoxy-3-pyridyl)isoxazol-3-yl]-[4-(1-methylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (P-5),

[0337] [5-(3,5-Difluoro-2-pyridyl)isoxazol-3-yl]-[racemic-(1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]methanone (P-6),

[0338] [5-(3,5-Difluoro-2-pyridyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (P-7),

[0339] [5-(2,6-Difluoro-3-pyridyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol-4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (P-8), or

[0340] [[5-(2,6-Difluoro-3-pyridyl)-1,3,4-thiadiazol-2-yl]-[racemic-(1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]methanone (P-9).

[0341] The compounds of formula (I) according to the invention can be prepared as shown in the following scheme, wherein, unless otherwise stated, the definition of each variable is as defined above for the compounds of formula (I).

[0342] The compounds of formula (I) according to the invention can be prepared as shown in the following Schemes 1 to 20, wherein, unless otherwise stated, the definition of each variable is as defined above for the compounds of formula (I).

[0343] In particular, the compounds of formula (I) wherein R 4 and R 6 are hydrogen and R5 (wherein R is hydrogen or methyl) can be prepared as shown in Schemes 1 to 7 below, wherein, unless otherwise stated, the definition of each variable is as defined above for the compound of formula (I).

[0344] In any of the following schemes, the presence of one or more possible asymmetric carbon atoms in the compound of formula (I) according to the present invention means that these compounds can exist in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms.

[0345] The compound of formula (I) can be prepared by those skilled in the art according to known methods. More specifically, the compound of formula (I) can be prepared from a compound of formula (III) or a salt thereof (wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2 are as defined for the compound of formula (I)) by reaction with a compound of formula (II) (wherein A 1 、A 2 、A 3 and Z 1 are as defined for the compound of formula (I)). This reaction is shown in Scheme 1.

[0346]

[0347] Scheme 1

[0348] In Scheme 1, the compound of formula (II) (wherein A 1 、A 2 、A 3 and Z 1 are as defined for the compound of formula (I)) is activated to a compound of formula (IIa) by a method known to those skilled in the art and described, for example, in Tetrahedron 2005, 61(46), 10827 - 10852. For example, the compound of formula (IIa) (wherein X 0is formed by treating a compound of formula (II) with, for example, oxalyl chloride or thionyl chloride in an inert solvent such as dichloromethane or tetrahydrofuran (THF) in the presence of a catalytic amount of N,N-dimethylformamide (DMF) at a temperature between 20 °C and 100 °C, preferably at 25 °C. Optionally in the presence of a base such as triethylamine or pyridine, with a compound of formula (III) wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2 are as defined for the compound of formula (I)), to yield a compound of formula (I). Alternatively, the compound of formula (I) can be prepared by treating a compound of formula (II) with dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) or 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) in an inert solvent such as pyridine, DMF, acetonitrile, CH2Cl2 or THF at a temperature between 30 °C and 180 °C, optionally in the presence of a base such as triethylamine, to obtain an activated compound of formula (IIa) wherein X 0 is G 1 、G 2 or G 3 as described in Scheme 1a). Finally, the compound of formula (II) can also be activated by reaction with a coupling reagent such as propanephosphonic anhydride (T3P) to afford a compound of formula (IIa) wherein X 0 is G 4 as described in Scheme 1a), as described, for example, in Synthesis 2013, 45, 1569. Further reaction with an amine (or its salt) of a compound of formula (III) gives a compound of formula (I).

[0349]

[0350] wherein, indicates a bond to the C(=O) group

[0351] Scheme 1a

[0352] Compounds having formula (II) can be prepared from compounds having formula (IIb) wherein A 1 、A 2 、A 3 is N and Z 1 is as described in formula (I), and R 0 is C1-C4 alkyl) by ester hydrolysis. A variety of conditions can be used, such as, for example, aqueous sodium hydroxide or lithium hydroxide, and organic water-miscible solvents like THF, dimethoxyethane, methanol, or ethanol. Such ester hydrolyses are well known to those skilled in the art. Compounds having formula (IIb) can also be directly converted to compounds having formula (I) by reacting a compound having formula (IIb) with a compound having formula (III) in an inert solvent (such as toluene or dichloromethane) in the presence of trimethylaluminum or a trimethylaluminum-DABCO complex. Such reactions have been reported in the literature (see Tetrahedron Lett. [Tetrahedron Letters] 1977, 4171-4174, Tetrahedron Lett. [Tetrahedron Letters] 2006, 5767-5769, and the references cited therein). Compounds having formula (II) and (IIb) are commercially available or can be synthesized as described below.

[0353] For example, a compound having formula (IIIa) wherein R 4 and R 6 are hydrogen, R 5 is hydrogen or methyl and R 1 、R 2 、R 3 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2 are as defined for the compounds having formula (I)) can be prepared from a compound having formula (IVa) wherein R 4 and R 6 are hydrogen, R 5 is hydrogen or methyl and R 1 、R 2 、R 3 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2It is prepared by treatment in a protic solvent (such as methanol or ethanol, etc.) with a reducing agent (such as NaBH3CN) and an acid (such as hydrochloric acid or acetic acid) as defined for the compounds of formula (I). Such reactions are well known in the literature and similar reactions have been described, for example, in Deng, Zeping et al., CN 103772278 and Synthesis (1979), 4, 281 - 283. Alternatively, the compounds of formula (IIIa) can be prepared by reduction of the compounds of formula (IVa) with hydrogen in the presence of a suitable metal catalyst (such as Pd, Ir, Rh) and a suitable ligand (such as diphosphine [1,2 - bis(diphenylphosphino)ethane (dppe), 1,3 - bis(diphenylphosphino)propane (dppp) or 1,4 - bis(diphenylphosphino)butane (dppb)]). Similar reactions have been reported, for example, in React. Kinet. Cat. Lett. 2007, 92, 99 - 104. The reaction is shown in Scheme 2.

[0354]

[0355] Scheme 2

[0356] As shown in Scheme 3, by methods known to those skilled in the art and by those described in Scheme 1, by treatment of a compound of formula (IIIb) (wherein R 0 is a leaving group such as a halogen and R 0 is a C1 - C6 alkyl) with a compound of formula (VI), a compound of formula (IIIb) (wherein R 4 , R 6 and R 7 are hydrogen, R 5 is hydrogen or methyl and R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , R 11 , B 1 and B 2 are as defined for the compounds of formula (I)) can be converted into a compound of formula (V) (wherein R 4 , R 6 and R 7 are hydrogen, R 5 is hydrogen or methyl and R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , R11 and B 1 and B 2 is as defined for compounds of formula (I)). Alternatively, a compound of formula (V) can be prepared by treating with an acid anhydride of formula (R 0 (CO)2O, where R 0 is C1-C6 alkyl) in an inert solvent (such as dichloromethane, THF or 2-methyl-THF), optionally in the presence of a base (such as triethylamine or dimethylaminopyridine), at a temperature between 0 °C and 60 °C. Then, at low temperature (e.g., -78 °C) to room temperature, in an inert polar solvent (such as THF or 2-methyl-THF), the compound of formula (V) is metallated with a base (such as an alkylmetal base, such as tert-butyllithium) and an additive (such as N,N,N′,N′-tetramethylethylenediamine (TMEDA)). Subsequently, an electrophile of formula R 7 -X 0 (where X 0 is as previously defined, and R 7 is C1-C4 alkyl, C1-C4 alkylcarbonyl, C1-C4 alkoxycarbonyl, N-methoxy-N-methyl-carbonyl, C1-C4 alkylaminocarbonyl, di(C1-C4 alkyl)aminocarbonyl, or C3-C6 cycloalkyl, where the C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy) is used to treat the anion of formula (V) formed under such conditions to obtain a compound of formula (Va) (where R 4 and R 6 are hydrogen, R 5 is hydrogen or methyl, R 0 is C1-C6 alkyl and R 1 、R 2 、R 3 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2 is as defined for compounds of formula (I)). The reaction is shown in Scheme 3.

[0357]

[0358] Scheme 3

[0359] The compound of formula (Va) can be converted to a compound of formula (IIIa) (where R 4 and R 6is hydrogen, R 5 is hydrogen or methyl and R 1 、R 2 、R 3 、R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2 are as defined for the compounds of formula (I)). For example, a compound of formula (Va) (wherein R 0 is tert-butyl) can be treated with an organic or inorganic acid (such as trifluoroacetic acid or HCl) to obtain a compound of formula (IIIa). The reaction is shown in Scheme 4.

[0360]

[0361] Scheme 4

[0362] A compound of formula (IVa) (wherein R 4 and R 6 are hydrogen, R 5 is hydrogen or methyl and R 1 、R 2 、R 3 、R 7 、R 8 、R 9 、B 1 and B 2 are as defined for the compounds of formula (I)) can be prepared by reacting a compound of formula (VIII) (wherein R 1 、R 2 and R 3 are as defined for the compounds of formula (I), and X 0 is a halogen, preferably chlorine, bromine or iodine) with a compound of formula (VII) (wherein R 5 is hydrogen or methyl and R 7 、R 8 、R 9 、R 10 、R 11 、B 1 and B 2 are as defined for the compounds of formula (I)) by means of a C-C bond forming reaction typically under palladium-catalyzed (alternatively nickel-catalyzed) cross-coupling conditions. The reaction is shown in Scheme 5.

[0363]

[0364] Scheme 5

[0365] The Suzuki-Miyaura cross-coupling reaction between a compound of formula (VIII) and a compound of formula (VII) is well known to those skilled in the art and is generally carried out in the presence of a palladium catalyst (such as tetrakis(triphenylphosphine)palladium(0) or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex) and a base (such as sodium carbonate or potassium carbonate) in a solvent (such as N,N-dimethylformamide, dioxane or dioxane-water mixture) at a temperature between room temperature and 160 °C, optionally under microwave heating conditions and preferably under an inert atmosphere. Such reactions have been reviewed, for example, in J. Organomet. Chem. [Journal of Organometallic Chemistry] 1999, 576, 147-168. Those skilled in the art will also recognize that the reaction can be reversed, i.e., by reacting a compound of formula (X) (wherein R 1 、R 2 and R 3 are as defined for the compound of formula (I)) with a compound of formula (IX) (wherein R 5 is hydrogen or methyl, R 7 、R 8 、R 9 、B 1 and B 2 are as defined for the compound of formula (I), and X 0 is a halogen, preferably chlorine, bromine or iodine) to provide a compound of formula (IVa) (wherein R 4 and R 6 are hydrogen, R 5 is hydrogen or methyl and R 1 、R 2 、R 3 、R 7 、R 8 、R 9 、B 1 and B 2 are as defined for the compound of formula (I)). The reaction is shown in Scheme 6.

[0366]

[0367] Scheme 6

[0368] Another cross-coupling chemical reaction, namely C-H activation, can also be used to prepare a compound of formula (IVa) (wherein R 4 and R 6 are hydrogen, R 5 is hydrogen or methyl and R 1 、R 2 、R 3 、R 7, R 8 , R 9 , B 1 and B 2 are as defined for the compounds of formula (I) (Scheme 7).

[0369]

[0370] Scheme 7

[0371] As shown in Scheme 7, a compound of formula (IX) in which R 5 is hydrogen or methyl, R 7 , R 8 , R 9 , B 1 and B 2 are as defined for the compounds of formula (I), and X 0 is a halogen, preferably chlorine, bromine or iodine) is reacted with a compound of formula (XI) in which R 1 , R 2 and R 3 are as defined for the compounds of formula (I)) in the presence of a palladium catalyst (typically palladium acetate Pd(OAc)2), a suitable ligand (such as 1,10-phenanthroline), in the presence of a base (such as cesium carbonate or potassium carbonate), in an inert solvent (such as chlorobenzene, toluene or xylene), at a temperature between room temperature and 180 °C, optionally under microwave heating conditions, preferably under an inert atmosphere. Similar reactions have been reported in the literature, for example in Chem. Sci. [Chemical Science] 2013, 4, 2374 - 2379.

[0372] In addition, the compound of formula (III) can be prepared from the compound of formula (XVI) (Scheme 8).

[0373]

[0374] Scheme 8

[0375] As shown in Scheme 8, the compound of formula (III) can be prepared by a person skilled in the art from a compound of formula (XVI) in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , B 1 and B 2 are as defined for the compounds of formula (I), and R 01It can be prepared by a carbamate deprotection reaction of a member that can be a common carbamate protecting group substituent, such as methyl, tert-butyl, allyl, 2,2,2-trichloroethyl, or benzyl). For example, when R 01 is methyl, a suitable solvent (such as dichloromethane) and a suitable reagent (such as trimethylsilyl iodide) can be used to obtain the product when heated at a temperature between room temperature and 200 °C, preferably between 20 °C and the boiling point of the reaction mixture, as described, for example, in J. Am. Chem. Soc. [Journal of the American Chemical Society] 1992, 114, 5959. The compound having formula (III) thus obtained is converted to the compound having formula (I) (Scheme 1).

[0376] A compound having formula (XVI) wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 and B 2 are as defined for the compound having formula (I), and wherein R 01 is as described above) can be formed by subjecting an aldehyde having formula (XV) (including formaldehyde in its different forms) wherein R 7 is as defined for the compound having formula (I) to a Pictet-Spengler reaction with a compound having formula (XIV) wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 8 、R 9 、B 1 and B 2 are as defined for the compound having formula (I), and wherein R 01 is as described above) in the presence of an acid in a suitable solvent, for example as described in Tetrahedron [Tetrahedron] 1987, 43, 439 (Scheme 9).

[0377]

[0378] Scheme 9

[0379] A compound having formula (XIV) wherein R 1 、R 2 、R3 , R 4 , R 5 , R 6 , R 8 , R 9 , B 1 and B 2 is as defined for the compounds of formula (I), and wherein R 01 is as described above) can be prepared by optionally reacting an amine of formula (XIII) (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , B 1 and B 2 is as defined for the compounds of formula (I)) with a suitable protecting reagent (such as methyl chloroformate) in the presence of a base (such as triethylamine or pyridine) in a suitable solvent (such as dichloromethane) at a temperature between -20 °C and the boiling point of the mixture, as described, for example, in Org. Biomol. Chem. [Organic & Biomolecular Chemistry] 2016, 14, 6853. The reaction is shown in Scheme 10.

[0380]

[0381] Scheme 10

[0382] A compound of formula (XIII) or a salt thereof (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , B 1 and B 2 is as defined for the compounds of formula (I)) can be obtained by those skilled in the art by reacting a nitrile of formula (XII) (wherein R 1 , R 2 , R 3 , R 4 , R 8 , R 9 , B 1 and B 2is prepared by reacting (as defined for compounds of formula (I)) with a suitable nucleophile (such as (dimethylsulfide)dihydroboron (BMS)) in a suitable aprotic solvent (such as tetrahydrofuran), for example as described in J. Org Chem. [Journal of Organic Chemistry] 1981, 47, 3153. Alternatively, a Grignard reagent R 5 MgBr or R 6 MgBr (where R 5 and R 6 are as defined for compounds of formula (I)) can be added, sequentially or simultaneously, as a nucleophile to a compound of formula (XII) to allow the preparation of a more highly substituted amine of formula (XIII). Such Grignard addition to a nitrile is carried out in an inert solvent (such as diethyl ether, tert-butyl methyl ether and cyclopentyl methyl ether) in the presence of a Lewis acid (such as Ti(O- i Pr)4) (see Synlett [Synthesis Letters] 2007, (4), 652 - 654).

[0383] This reaction is shown in Scheme 11.

[0384]

[0385] Scheme 11

[0386] Alternatively, a compound of formula (XIII) (where R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 8 、R 9 、B 1 and B 2 are as defined for compounds of formula (I), and where R 5 、R 6 is hydrogen), i.e., a compound of formula (XIIIa), can be prepared by one skilled in the art by reacting an unsaturated nitro compound of formula (XIIIb) (where R 1 、R 2 、R 3 、R 4 、R 8 、R 9 、B 1 and B 2 are as defined for compounds of formula (I)) with a compound of formula (VIII) (where R 1 、R 2 and R 3 are as defined for compounds of formula (I), and X0 reacts with a halogen, preferably iodine), followed by reduction of the compound of formula (XIIIb) (wherein R 1 , R 2 , R 3 , R 4 , R 8 , R 9 , B 1 and B 2 are as defined for the compound of formula (I)) to the compound of formula (XIIIa). Such a reaction is described in the Preparation section under Example P1 Step 8 (Option B - Step A and Step B). The reaction is shown in Scheme 12.

[0387]

[0388] Scheme 12

[0389] The compound of formula (XII) (wherein R 1 , R 2 , R 3 , R 4 , R 8 , R 9 , B 1 and B 2 are as defined for the compound of formula (I)) can be prepared by those skilled in the art according to known methods. More specifically, the compound of formula (XII) and its intermediates can be prepared from the compound of formula (XVII), as shown in Scheme 13.

[0390]

[0391] Scheme 13

[0392] For example, the compound of formula (XII) (wherein R 1 , R 2 , R 3 , R 8 , R 9 , B 1 and B 2 are as defined for the compound of formula (I), and R 4 is not hydrogen) can be prepared by those skilled in the art by using a strong base (such as n-butyllithium or sodium hydride) in an inert solvent (such as tetrahydrofuran) at cryogenic temperature, followed by addition of a suitable alkylating agent R 4 -X (wherein R 4 is a C1-C4 alkyl and X is a halogen) (such as iodomethane) to the compound of formula (XIIa) (wherein R 1 , R 2 , R3 , R 8 , R 9 , B 1 and B 2 is prepared by deprotonation as defined for compounds of formula (I).

[0393] A compound of formula (XIIa) wherein R 1 , R 2 , R 3 , R 8 , R 9 , B 1 and B 2 is as defined for compounds of formula (I)) can be prepared by treating an alcohol of formula (XVII) with trimethylsilyl cyanide (TMSCN) in the presence of a base (such as lithium carbonate) in a non-polar solvent (such as dichloromethane) at a temperature between 0 °C and the boiling point of the reaction mixture. Such transformations are well known in the literature under various conditions, for example as described in Org. Lett. [Organic Letters] 2008, 10, 4570 and references therein. The reaction is shown in Scheme 13.

[0394] A compound of formula (III) wherein B 1 is CR 10 , B 2 is CR 11 , R 1a is C1-C4 alkyl, R 2a is hydrogen, halogen, or C1-C4 alkyl, R 3 is hydrogen, R 4a , R 5a , R 6a , R 7a is hydrogen or C1-C4 alkyl, and R 8 , R 9 , R 10 and R 11 is as defined for compounds of formula (I)), i.e., an alternative synthesis of a compound of formula (IIIc) is described below.

[0395]

[0396] A compound of formula (IIIc) can also be prepared by

[0397]

[0398] Treating a compound of formula (XVIII) (wherein R 1 is a C1-C4 alkyl group, R 2 is hydrogen, halogen, or a C1-C4 alkyl group, R 3 is hydrogen, R 4 is hydrogen or a C1-C4 alkyl group, R 5 、R 6 、R 7 is hydrogen or a C1-C4 alkyl group, and R 8 、R 9 、R 10 and R 11 are as previously defined) with a strong acid (such as sulfuric acid, hydrochloric acid, hydrobromic acid, trifluoroacetic acid, trifluoromethanesulfonic acid (trifllic), or methanesulfonic acid, etc.) or a Lewis acid (such as aluminum trichloride or bismuth(III) trifluoromethanesulfonate) in an inert solvent (such as chlorobenzene, nitrobenzene) at a temperature between 0 °C and 180 °C to produce a compound of formula (IIIc). As described previously, these compounds are converted into compounds of formula (I). Those skilled in the art will recognize that such cyclization can proceed through intermediates, such as compounds of formula (XIX),

[0399]

[0400] and (when R 4 is methyl) compounds of formula (XX)

[0401]

[0402] and wherein the substituents R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 are as defined for compounds of formula (I). Depending on the reaction conditions, these intermediates can be isolated and / or further directly converted into compounds of formula (IIIc). Those skilled in the art will also recognize that when R 7 is a C1-C4 alkyl group, a mixture of diastereomeric racemates - (cis-IIIc) and racemic - (trans-IIIc) can be obtained, and the ratio can be controlled to direct the preferential formation of one isomer over the other (Scheme 14).

[0403]

[0404] Scheme 14

[0405] The intermediates (XVIII), (XIX) and (XX) are new and thus form part of the present invention.

[0406] Compounds (XVIII), (XIX) and (XX) can be prepared as shown in Scheme 15 below and as described in the Experimental section.

[0407]

[0408] Scheme 15

[0409] As shown in Scheme 15, in the presence of a base (such as Et3N), in an inert solvent (such as DMF), a compound of formula (XXII) is alkylated with a benzylamine of formula (XXI). The compound (XXIII) thus obtained can be isolated or directly treated in situ with BOC-anhydride to give a compound of formula (XXIV). The compound of formula (XXIV) can be reduced with a hydride source (e.g., NaBH4 in MeOH / THF) to give the target molecule (XVIIIb), which can then be cyclized with, for example, camphorsulfonic acid in EtOAc to give a compound of formula (XIXb). Alternatively, the compound of formula (XXIV) can be reacted with a Grignard reagent R 4 MgBr in an inert ethereal solvent (such as THF) to give a compound of formula (XVIIIa), which can be cyclized with camphorsulfonic acid in, for example, EtOAc to give a compound of formula (XIXa). In compounds (XIX) and (XVIII), R 1a is C1-C4 alkyl, R 2a is hydrogen, halogen, or C1-C4 alkyl, R 4a is hydrogen or C1-C4 alkyl, R 5a , R 6a and R 7a are hydrogen or C1-C4 alkyl, and R 8 , R 9 , R 10 and R 11 are as defined for the compound of formula (I).

[0410] It should be noted that there are additional aspects to this Friedel-Crafts chemical reaction. If the chemical reaction starts with a chiral amine (XXIa) (e.g., R 7 is C1-C4 alkyl), the final compound of formula (I) will retain its stereochemistry. This is shown in Scheme 16 below, for when R 7 is methyl:

[0411]

[0412]

[0413] Compounds having formula (XVII) can be prepared by methods known to those skilled in the art. Compounds having formulae (XXI) and (XXII) can be readily prepared by those skilled in the art or can be purchased.

[0414] Compounds having formula II, where A 1 is N, A 2 is O, A 3 is CH, and Z 1 is as defined for compounds having formula (I), i.e., compounds having formula (IIc), can be prepared as shown in Scheme 17.

[0415]

[0416] Scheme 17

[0417] As shown in Scheme 17, compounds having formula (IIc), where Z 1 is as defined for compounds having formula (I), and X 05 is a C1-C4 alkyl, can be prepared by hydrolyzing compounds having formula (IIb) by treatment with, for example, an alkaline earth metal hydroxide in water or in a water-miscible organic solvent such as THF, methanol, ethanol, etc. Such ester hydrolysis is well known to those skilled in the art. Compounds having formula (IIb) can be obtained by treating compounds having formula (XXVII), where Z 1 is as defined for compounds having formula (I), and X 05 is a C1-C4 alkyl, with hydroxylamine hydrochloride in a polar solvent such as ethanol and optionally in the presence of a base such as triethylamine, K2CO3, etc.

[0418] Compounds having formula (XXVII) are obtained by reacting compounds having formula (XXV), where Z 1 is as defined for compounds having formula (I), with compounds having formula (XXVI) or compounds having formula (XXVIa), where X 05is prepared by reacting a compound of formula (XXVIa) with a compound of formula (XXVIII) optionally in the presence of a base (such as pyridine or triethylamine) in a solvent (such as acetonitrile, chloroform or THF). Such reactions have been reported, for example, in Bioorg. Med. Chem. [Bioorganic and Medicinal Chemistry] 2016, 24(22), 5693 - 5701 and CN 114933573. The compound of formula (XXVIII) (wherein Z

[0419] The compound of formula (II) wherein A 1 is O, A 2 and A 3 is N, and Z 1 is as defined for the compound of formula (I)), i.e., the compound of formula (IIe), can be prepared as shown in Scheme 18.

[0420]

[0421] Scheme 18

[0422] As shown in Scheme 18, the compound of formula (IIe) is obtained by ester hydrolysis of the compound of formula (IId) as previously described in Scheme 17. The compound of formula (IId) (wherein Z 1 is as defined for the compound of formula (I), and X 05 is C1 - C4 alkyl) is prepared by reacting a compound of formula (XXVIa) with a compound of formula (XXVIII) optionally in the presence of a base (such as pyridine or triethylamine) in a solvent (such as acetonitrile, chloroform or THF). Such reactions have been reported, for example, in Bioorg. Med. Chem. [Bioorganic and Medicinal Chemistry] 2016, 24(22), 5693 - 5701 and CN 114933573. The compound of formula (XXVIII) (wherein Z 1(as defined for the compounds of formula (I)) can be obtained by treating a compound of formula (XXIX) with hydroxylamine hydrochloride in a polar solvent (such as ethanol) in the presence of a base (such as K2CO3 or Na2CO3). The reaction can also be carried out using a solution of hydroxylamine in the absence of a base. Such reactions have been described, for example, in Bioorg. Med. Chem. Lett. [Bioorganic & Medicinal Chemistry Letters] 2020, 30(21), 127508 and Bioorg. Med. Chem. Lett. [Bioorganic & Medicinal Chemistry Letters] 2016, 26(23), 5679 - 5684.

[0423] A compound of formula (XXVIII) wherein Z 1 (as defined for the compounds of formula (I)) can also be prepared by a Pd - catalyzed one - pot cyanation and amidoximation of a compound of formula (XXX) wherein Z 1 (as defined for the compounds of formula (I)), as described, for example, in Org. Biomol. Chem. [Organic & Biomolecular Chemistry] 2015, 13(9), 2541 - 2545.

[0424] A compound of formula (II) wherein A 1 and A 2 is N, and A 3 is O, and Z 1 is as previously described (i.e., a compound of formula (IIg)), and A 1 and A 2 is N, and A 3 is S, and Z 1 (as defined for the compounds of formula (I) (i.e., a compound of formula (IIi))) can be prepared as shown in Scheme 19.

[0425]

[0426] Scheme 19

[0427] As shown in Scheme 19, the compounds of formula (IIg) and (IIi) are obtained by ester hydrolysis of (IIf) and (IIg), respectively. In the latter compound, X 05 and Z 1is as described previously. The compound having the formula (IIf) can be obtained by dehydration of the compound having the formula (IIf) with the compound having the formula (XXXI). The compound having the formula (XXXI) is obtained by acylation of the hydrazide having the formula (XXXII) with the compound having the formula (XXVIa). Such a sequence of reactions to produce oxadiazole is well known to those skilled in the art. Similar reactions are described in Bioorg. Med. Chem. Lett. [Bioorganic & Medicinal Chemistry Letters] 2005, 15, 1423 - 1428 and WO 2006 / 044617. The compound having the formula (XXXI) can also be prepared by the reaction of the activated carboxylic acid having the formula (XXXIIIa) (where Z 1 is as defined for the compound having the formula (I), and X 0 is as described in Scheme 1 / Scheme 1a respectively) with the compound having the formula (XXXIV). The compound having the formula (XXXIIIa) can be prepared from the corresponding acid having the formula (XXXIII) as described in Scheme 1. Such reactions are described, for example, in J. Prakt. Chem. [Journal of Practical Chemistry] 1985, 327, 109 - 116. The compound having the formula (IIh) can also be prepared from the common intermediate having the formula (XXXI) (where Z 1 is as defined for the compound having the formula (I), and X 05 is as described previously) by treatment with Lawesson's reagent or pure phosphorus pentasulfide, or in an inert solvent (such as toluene or xylene). Similar reactions are known in the literature (see, for example, WO 2010 / 006713, WO 2009 / 149858 and J. Org. Chem. [Journal of Organic Chemistry] 1961, 26, 4410 - 12).

[0428] The compound having the formula (II) (where A 1 is O, A 2 is N, A 3 is methylene, and Z 1 is as defined for the compound having the formula (I)), namely the compound having the formula (IIk), can be prepared, for example, as shown in Scheme 20.

[0429]

[0430] Scheme 20

[0431] As shown in Scheme 20, the compound having the formula (IIk) is readily obtained by hydrolysis of the ester having the formula (IIj) by methods known to those skilled in the art and as described above. The compound having the formula (IIj) can be obtained by the reaction of a compound having the formula (XXXV) with a compound having the formula (XXXVI) in the presence of an oxidizing agent (such as (diacetoxyiodo)benzene or N-chlorosuccinimide) in an inert solvent (such as methanol or DMF). Such reaction sequences have been described, for example, in J. Het. Chem. [Journal of Heterocyclic Chemistry] 2013, 50(4), 774 - 780 and J. Chin. Chem. Soc. [Chinese Chemical Society Journal] 2007, 54(3), 643 - 652. The compound having the formula (XXXV) is readily prepared by treating a compound having the formula (XXXVII) (where Z 1 is as defined for the compound having the formula (I)) with hydroxylamine under conditions well known to those skilled in the art.

[0432] The salts of the compound having the formula (I) can be prepared in a manner known per se. Thus, for example, the acid addition salts of the compound having the formula (I) are obtained by treatment with a suitable acid or a suitable ion-exchange reagent, and the salts with bases are obtained by treatment with a suitable base or a suitable ion-exchange reagent.

[0433] The salts of the compound having the formula (I) can be converted in a conventional manner into the free compound (I), acid addition salts (for example by treatment with a suitable basic compound or a suitable ion-exchange reagent) and salts with bases (for example by treatment with a suitable acid or a suitable ion-exchange reagent).

[0434] The salts of the compound having the formula (I) can be converted in a manner known per se into other salts of the compound having the formula (I), acid addition salts, for example into other acid addition salts, for example by treating a salt of an inorganic acid (such as a hydrochloride) with a suitable metal salt of an acid (such as a salt of sodium, barium or silver, for example silver acetate) in a suitable solvent in which the inorganic salt formed (such as silver chloride) is insoluble and thus precipitates from the reaction mixture.

[0435] Depending on the procedure or reaction conditions, the compound having the formula (I) with salting properties can be obtained in free form or in the form of a salt.

[0436] The compounds of formula (I) and, where appropriate, their tautomers (in each case in free form or in salt form) can be present in the form of one of the possible isomers or as a mixture of these isomers, for example in the form of pure isomers (such as enantiomers and / or diastereoisomers) or as a mixture of isomers (such as a mixture of enantiomers, for example a racemate, or a mixture of diastereoisomers), depending on the number of asymmetric carbon atoms present in the molecule, the absolute and relative configuration and / or depending on the configuration of non-aromatic double bonds present in the molecule. The present invention relates to the pure isomers as well as to all possible mixtures of isomers, and in each case in the context, even in each case where no stereochemical details are specifically mentioned, should be understood in this sense.

[0437] Mixtures of diastereoisomers or racemate mixtures of the compounds of formula (I) in free form or in salt form (the obtaining of which can depend on the starting materials and procedures chosen) can be separated in a known manner into the pure diastereoisomers or racemates on the basis of the physicochemical differences of these components, for example by fractional crystallization, distillation and / or chromatography.

[0438] Mixtures of enantiomers (such as racemates) which can be obtained in a similar manner can be resolved into the optical enantiomers by known methods, for example by recrystallization from an optically active solvent; by chromatography on a chiral adsorbent, for example high performance liquid chromatography (HPLC) on acetylcellulose; by cleavage with a specific immobilized enzyme with the aid of a suitable microorganism; via the formation of inclusion compounds, for example using a chiral crown ether, in which only one enantiomer is complexed; or by conversion into salts of diastereoisomers, for example by reacting the basic end product racemate with an optically active acid (such as a carboxylic acid, for example camphoric acid, tartaric acid or malic acid, or a sulfonic acid, for example camphorsulfonic acid), and separating the mixture of diastereoisomers which can be obtained in this way, for example by fractional crystallization based on their different solubilities, so as to obtain diastereoisomers, from which the desired enantiomer can be liberated by the action of a suitable reagent (such as a basic reagent).

[0439] Pure diastereoisomers or enantiomers can be obtained according to the invention not only by separating suitable mixtures of isomers, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials having suitable stereochemistry.

[0440] If the individual components have different biological activities, it is advantageous in each case to separate or synthesize the biologically more active isomers, such as enantiomers or diastereoisomers or mixtures of isomers, such as mixtures of enantiomers or mixtures of diastereoisomers.

[0441] As an example, a compound having more than one asymmetric carbon atom may exist in diastereoisomeric forms, which may optionally be separated using, for example, supercritical fluid chromatography (SFC) chromatography with a chiral column. Such diastereoisomers may exhibit different fungicidal activity profiles, but all isomers and diastereoisomers form part of the present invention.

[0442] The compound having the formula (I) has three chiral carbon atoms (three stereocenters, where the asterisk (*) indicates a chiral carbon atom), such that eight available stereoisomers exist. These eight stereoisomers consist of four sets of enantiomers.

[0443]

[0444] For a compound having the formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , B 1 , B 2 , A(A 1 , A 2 , A 3 ), and Z 1 are as defined for a compound having the formula (I), and wherein R 7 is not hydrogen, the relationship between enantiomers and diastereoisomers is shown in Scheme 21.

[0445]

[0446] Scheme 21

[0447] Those skilled in the art are well aware of these diastereoisomers and enantiomers of the formula (I) (as shown in Scheme 21) (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , B 1 , B 2 , A(A 1 , A 2 , A 3 ), and Z 1 are as defined for the formula (I), and wherein R7 is not hydrogen) is within the scope of the present invention.

[0448] For a compound having formula (I), wherein R 1 is methyl, R 3 , R 4 , R 5 , R 6 is hydrogen and R 2 , R 7 , R 8 , R 9 , B 1 , B 2 , A(A 1 , A 2 , A 3 ), and Z 1 is as defined for a compound having formula (I), and wherein R 7 is not hydrogen, the relationship between the enantiomers and diastereoisomers is shown in Scheme 22.

[0449]

[0450] Scheme 22

[0451] In one embodiment, a compound having formula (I) (wherein R 1 is methyl, R 3 , R 4 , R 5 , R 6 is hydrogen and R 2 , R 7 , R 8 , R 9 , B 1 , B 2 , A(A 1 , A 2 , A 3 ), and Z 1 is as defined for a compound having formula (I), and wherein R 7 is not hydrogen), the pyrazole - moiety and R 7 are cis - related to each other.

[0452] A compound having formula (I) (wherein R 1 is methyl, R 3 , R 4 , R 5 , R 6 is hydrogen and R 2 , R 7 , R 8 , R 9 , B 1 , B 2 , A(A1 , A 2 , A 3 ), and Z 1 is as defined for the compounds of formula (I), and wherein R 7 is not hydrogen) of the cis-isomer is shown in Scheme 23.

[0453]

[0454] Scheme 23

[0455] Preferably, the compounds of formula (I) wherein R 1 is methyl, R 3 , R 4 , R 5 , R 6 is hydrogen and R 2 , R 7 , R 8 , R 9 , B 1 , B 2 , A(A 1 , A 2 , A 3 ), and Z 1 is as defined for the compounds of formula (I), and wherein R 7 is not hydrogen), the pyrazole moiety and R 7 are cis-related to each other, as shown in Scheme 23.

[0456] The compounds of formula (I) and, where appropriate, their tautomers (in each case in free form or in salt form) can also, if appropriate, be obtained in the form of hydrates and / or include other solvents, such as those which can be used to crystallize the compounds present in solid form.

[0457] As already indicated, surprisingly, it has now been found that, for practical purposes, the compounds of formula (I) according to the invention have a very advantageous level of biological activity for protecting plants against diseases caused by fungi.

[0458] Compounds of formula (I) according to the present invention can be used in the agricultural sector and related fields of use, for example, as active ingredients for controlling phytopathogens, or on inanimate materials for controlling spoilage microorganisms or organisms potentially harmful to humans. These new compounds are characterized by excellent activity at low application rates, good plant tolerance, and environmental safety. They have very useful therapeutic, prophylactic, and systemic properties and can be used to protect many cultivated plants. Compounds of formula (I) can be used to inhibit or destroy pests that occur on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of different useful plant crops, while also protecting those later-growing plant parts from, for example, infestation by phytopathogenic microorganisms.

[0459] The present invention further relates to a method for controlling or preventing the infestation of plants or plant propagation materials and / or harvested food crops susceptible to microbial attack by treating the plants or plant propagation materials and / or harvested food crops, wherein an effective amount of a compound of formula (I) according to the present invention is applied to the plant, its parts, or its locus.

[0460] It is also possible to use the compounds of formula (I) according to the present invention as fungicides. As used herein, the term "fungicide" means a compound that controls, modifies, or prevents the growth of fungi. The term "fungicidally effective amount" when used means the amount of such a compound or combination of such compounds that is capable of having an effect on fungal growth. The effects of control or modification include all deviations from natural development, such as killing, arresting, etc., and prevention includes forming a barrier or other defense within or on the plant to prevent fungal infestation.

[0461] It is also possible to use the compounds of formula (I) according to the present invention as seed dressings for treating plant propagation materials (e.g., seeds, if fruits, tubers, or grains) or plant cuttings, for protecting against fungal infections and against phytopathogenic fungi present in the soil. The propagation materials can be treated with a composition comprising a compound of formula (I) before planting: for example, the seeds can be dressed before sowing. The active compound of formula (I) can also be applied to the grains (coating) 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 planting the propagation materials, for example, applied to the furrow of the seeds during sowing. The present invention also relates to such methods for treating plant propagation materials and to plant propagation materials so treated.

[0462] In addition, the compounds of formula (I) according to the present invention can be used to control fungi in related fields, for example, in the protection of industrial materials (including wood and wood-related technical products), in food storage, and in hygiene management.

[0463] In addition, the present invention can be used to protect non-living materials (such as wood, wall panels, and coatings) from fungal attack.

[0464] Compounds having formula (I) according to the present invention are effective, for example, against fungal and fungal vectors of diseases and phytopathogenic bacteria and viruses. These fungal and fungal vectors of diseases and phytopathogenic bacteria and viruses are, for example: Apophysomyces elegans, Alternaria species, Aphanomyces species, Ascochyta species, Aspergillus species (including Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, Aspergillus terreus), Aureobasidium species (including Aureobasidium pullulans), Blastomyces dermatitidis, Blumeria graminis, Bremia lactucae, Botryosphaeria species (including Botryosphaeria dothidea, Botryosphaeria obtusa), Botrytis species (including Botrytis cinerea), Candida species (including Candida albicans, Candida glabrata, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis), Cephaloascus fragrans, Ceratocystis species, Cercospora species (including Cercospora arachidicola), Cercosporidium personatum, Cladosporium species, Claviceps purpurea, Coccidioides immitis, Cochliobolus species, Colletotrichum species (including Colletotrichum musae), Cryptococcus neoformans, Diaporthe species, Didymella species, Drechslera species, Elsinoë species, Epidermophyton species, Erwinia amylovora, Erysiphe species (including Erysiphe cichoracearum), Eutypa lata, Fusarium species (including Fusarium culmorum, Fusarium graminearum, Fusarium langsethiae, Fusarium moniliforme, Fusarium oxysporum, Fusarium solani, Fusarium verticillioides), Gaeumannomyces graminis, Gibberella fujikuroi, Gloeodes pomigena, Gloeosporium musarum, Glomerella cingulata, Guignardia bidwellii, Gymnosporangium juniperi-virginianae, Helminthosporium species, Hemileia species, Histoplasma species (including Histoplasma capsulatumcapsulatum), red thread fungus, Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale, Microsporum species, Monilinia species, Mucor species, Mycosphaerella species (including Mycosphaerella graminicola, M. pomi), tree tip blight fungus, spruce fungus, Paracoccidioides species, Penicillium species (including Penicillium digitatum, Penicillium italicum), Myriogenospora species, Sclerospora species (including Sclerospora maydis, Sclerospora philippinensis, Sclerospora sorghi), Peronospora species, Septoria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Torrubiella species, Phoma species, Phomopsis viticola, Phytophthora species (including Phytophthora infestans), Plasmopara species (including Plasmopara halstedii, Plasmopara viticola), Pleospora species, Podosphaera species (including Podosphaera leucotricha), Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas species, Pseudoperonospora species (including Pseudoperonospora cubensis, Pseudoperonospora humuli), Pseudopeziza tracheiphila, Puccinia species (including Puccinia hordei, Puccinia recondita, Puccinia striiformis, Puccinia triticina), Sclerotinia species, Pyrenophora species, Pyricularia species (including Pyricularia oryzae), Pythium species (including Pythium ultimum), Ramularia species, Rhizoctonia species, Rhizomucor pusillus, Rhizopus arrhizus, Rhynchosporium species, Sporothrix species (including Scedosporium apiospermum, Scedosporium prolificans), Schizothyrium pomi, Sclerotinia species, Sclerotium species, Septoria species (including Septoria nodorum, Septoria tritici),Puccinia tritici, Sphaerotheca macularis, Sphaerotheca fusca (Sphaerotheca fuliginea), Sporothorix species, Stagonospora nodorum, Stemphylium species, Stereum hirsutum, Thanatephorus cucumeris, Thielaviopsis basicola, Tilletia species, Trichoderma species (including Trichoderma harzianum, Trichoderma pseudokoningii, Trichoderma viride), Trichophyton species, Typhula species, Uncinula necator, Urocystis species, Ustilago species, Venturia species (including Venturia inaequalis), Verticillium species, and Xanthomonas species.

[0465] The compounds of formula (I) according to the invention can be used, for example, for turf, ornamental plants such as flowers, shrubs, broad-leaved trees or evergreen plants such as conifers, and tree injection, pest management, etc.

[0466] Within the scope of the present invention, the target crops and / or useful plants to be protected typically include perennial and annual crops such as berry plants, e.g., blackberry, blueberry, cranberry, raspberry, and strawberry; cereals, e.g., barley, maize (corn), millet, oats, rice, rye, sorghum, triticale, and wheat; fiber plants, e.g., cotton, flax, hemp, jute, and sisal; field crops, e.g., sugar beet and fodder beet, coffee bean, hops, mustard, rapeseed (canola), poppy, sugar cane, sunflower, tea, and tobacco; fruit trees, e.g., apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear, and plum; grasses, e.g., Bermuda grass, bluegrass, bentgrass, centipede grass, foxtail, ryegrass, St. Augustine grass, and zoysia grass; herbs, such as basil, borage, chive, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage, and thyme; legumes, e.g., kidney bean, lentil, pea, and soybean; nuts, e.g., almond, cashew, groundnut, hazelnut, peanut, pecan, pistachio, and walnut; palm plants, e.g., oil palm; ornamental plants, e.g., flowers, shrubs, and trees; other trees, e.g., cacao tree, coconut tree, olive tree, and rubber tree; vegetables, e.g., asparagus, eggplant, broccoli, cabbage, carrot, cucumber, garlic, lettuce, zucchini, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach, and tomato; and vines, e.g., grape.

[0467] The term "useful plant" should be understood to also include useful plants that have been made tolerant to herbicides (such as bromoxynil) or classes of herbicides (such as HPPD inhibitors, ALS inhibitors such as flupyrsulfuron, prosulfuron, and trifloxysulfuron, EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) inhibitors, GS (glutamine synthetase) inhibitors, or PPO (protoporphyrinogen oxidase) inhibitors) by conventional breeding methods or genetic engineering. Examples of crops that have been made tolerant to imidazolinones (such as imazamox) by conventional breeding methods (mutation) are summer rape (canola). Examples of crops that have been made tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate-resistant and glufosinate-resistant maize varieties, which are commercially available under the Herculex and trade names.

[0468] The term "useful plant" should be understood to also include useful plants that have been so transformed by the use of recombinant DNA technology that they are capable of synthesizing one or more selectively acting toxins, such as those known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.

[0469] Examples of such plants are: (maize variety expressing the CryIA(b) toxin); YieldGard (maize variety expressing the CryIIIB(b1) toxin); YieldGard (maize variety expressing the CryIA(b) and CryIIIB(b1) toxins); (maize variety expressing the Cry9(c) toxin); Herculex (maize variety expressing the CryIF(a2) toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) conferring tolerance to the herbicide glufosinate); NuCOTN (cotton variety expressing the CryIA(c) toxin); Bollgard (cotton variety expressing the CryIA(c) toxin); Bollgard (cotton variety expressing the CryIA(c) and CryIIA(b) toxins); (cotton variety expressing the VIP toxin); (potato variety expressing the CryIIIA toxin); Nature- GT Advantage (GA21 glyphosate tolerance trait), CB Advantage (CB trait of Ostrinia nubilalis), RW (western corn rootworm trait) and

[0470] The term "crop" shall be understood to also include crop plants that have been so transformed by recombinant DNA techniques that they are capable of synthesizing one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, in particular those of the genus Bacillus.

[0471] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as δ-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins that colonize nematodes, such as Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, spider toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as streptomycete toxins, lectins, such as pea lectin, barley lectin or snowdrop lectin; agglutinins; protease inhibitors, such as trypsin inhibitor, serine protease inhibitor, potato proteinase inhibitor, cystatin, papain inhibitor; ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid-metabolizing enzymes, such as 3-hydroxy-steroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitor, HMG-COA-reductase, ion-channel blockers such as sodium-channel or calcium-channel blockers, juvenile hormone esterase, diuretic hormone receptor, stilbene synthase, bibenzyl synthase, chitinase and glucanase.

[0472] Furthermore, in the context of the present invention, δ-endotoxins (such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C) or vegetative insecticidal proteins (Vips) (such as Vip1, Vip2, Vip3 or Vip3A) should be understood to clearly also include hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are recombinantly produced by new combinations of different domains of those proteins (see, for example, WO 02 / 15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid substitutions, it is preferred to insert a protease recognition sequence that does not occur naturally into the toxin, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence was inserted into the Cry3A toxin (see WO 2003 / 018810).

[0473] Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed, for example, in EP-0374753, WO93 / 07278, WO 95 / 34656, EP 0427529, EP 0451878 and WO03 / 052073.

[0474] Methods for preparing such transgenic plants are generally known to those skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, in WO 95 / 34656, EP0367474, EP 0401979 and WO 90 / 13651.

[0475] The toxins contained in transgenic plants render the plants tolerant to harmful insects. Such insects can be present in any insect taxon but are particularly common among beetles (Coleoptera), dipterous insects (Diptera) and moths (Lepidoptera).

[0476] Transgenic plants containing one or more genes encoding insecticide resistance and expressing one or more toxins are known and some of them are commercially available. Examples of such plants are: (maize variety expressing the Cry1Ab toxin); YieldGard (maize variety expressing the Cry3Bb1 toxin); YieldGard (maize variety expressing the Cry1Ab and Cry3Bb1 toxins); (maize variety expressing the Cry9C toxin); Herculex (Maize variety expressing the Cry1Fa2 toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) conferring tolerance to the herbicide glufosinate); NuCOTN (Cotton variety expressing the Cry1Ac toxin); Bollgard (Cotton variety expressing the Cry1Ac toxin); Bollgard (Cotton variety expressing the Cry1Ac and Cry2Ab toxins); (Cotton variety expressing the Vip3A and Cry1Ab toxins); (Potato variety expressing the Cry3A toxin); GT Advantage (GA21 glyphosate tolerance trait), CB Advantage (Bt11 European corn borer (CB) trait) and

[0477] Further examples of such genetically modified crops are:

[0478] 1. Bt11 maize, from Syngenta Seeds SAS, Chemindel’Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Genetically modified maize that expresses a truncated Cry1Ab toxin by genetic engineering to make it resistant to the attack of the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides). Bt11 maize also expresses the PAT enzyme by genetic engineering to obtain tolerance to the herbicide glufosinate.

[0479] 2. Bt176 maize, from Syngenta Seeds, Chemindel’Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Genetically modified maize that expresses the Cry1Ab toxin by genetic engineering to make it resistant to the attack of the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides). Bt176 maize also expresses the enzyme PAT by genetic engineering to obtain tolerance to the herbicide glufosinate.

[0480] 3. MIR604 maize, from Syngenta Seeds, Chemindel’Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Maize that has insect resistance by expressing a modified Cry3A toxin by genetic engineering. This toxin is Cry3A055 modified by inserting a cathepsin-G protease recognition sequence. The preparation of such genetically modified maize plants is described in WO 2003 / 018810.

[0481] 4. MON 863 maize, from Monsanto Europe S.A., 270 - 272 Avenue de Tervuren, B - 1150 Brussels, Belgium, registration number C / DE / 02 / 9. MON 863 expresses the Cry3Bb1 toxin and is resistant to certain Coleoptera insects.

[0482] 5. IPC 531 cotton, from Monsanto Europe, 270 - 272 Avenue de Tervuren, B - 1150 Brussels, Belgium, registration number C / ES / 96 / 02.

[0483] 6. 1507 maize, from Pioneer Overseas Corporation, Avenue Tedesco, 7B - 1160 Brussels, Belgium, registration number C / NL / 00 / 10. Genetically modified maize expressing the protein Cry1F to obtain resistance to certain Lepidoptera insects and expressing the PAT protein to obtain tolerance to the herbicide glufosinate.

[0484] 7. NK603×MON 810 maize, from Monsanto Europe, 270 - 272 Avenue de Tervuren, B 1150 Brussels, Belgium, registration number C / GB / 02 / M3 / 03. Constituted by a conventionally bred hybrid maize variety through the hybridization of the genetically modified varieties NK603 and MON 810. NK603×MON 810 maize transgenicly expresses the protein CP4 EPSPS obtained from Agrobacterium sp. strain CP4, making it herbicide - tolerant (containing glyphosate), and also the Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki, making it resistant to certain Lepidoptera insects, including the European corn borer.

[0485] The compound having formula (I) according to the present invention can be used to control or prevent phytopathogenic diseases, in particular phytopathogenic fungi, such as Alternaria spp. on fruits, vegetables and potatoes; Botrytis cinerea on strawberries, tomatoes, sunflowers, leguminous crops, vegetables and grapes; Rhizoctonia solani on potatoes and vegetables; Uncinula necator on grapes; Cladosporium spp., Cercospora spp., Erysiphe cichoracearum and Didymella bryoniae on cucurbits; Pratylenchus brachyurus on cucurbits and solanaceous crops; Fusarium spp. on cereals; Leptosphaeria spp. on cereals; and yeast species on cereals.

[0486] As used herein, the term "locality" means the place where the plant grows in or on, or the place where the seeds of the cultivated plant are sown, or the place where the seeds are to be placed in the soil. It includes the soil, the seeds and the seedlings, together with the established vegetation.

[0487] The term "plant" refers to all the tangible parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves and fruits.

[0488] The term "plant propagation material" shall be understood to mean the reproductive parts of plants, such as seeds, which can be used for the propagation of plants, as well as vegetative material, such as cuttings or tubers (e.g. potatoes). Mention may be made, for example, of seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Mention may also be made of germinated plants and young plants which are to be transplanted after germination or after emergence. These young plants can be protected before transplantation by being treated completely or partially by drenching. Preferably, "plant propagation material" shall be understood to mean seeds.

[0489] The compounds of formula (I) according to the invention can be used in unmodified form or, preferably, together with auxiliaries conventionally employed in the art of formulation. For this purpose, they can be conveniently formulated in known manner as emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granules and also capsules, for example in polymeric substances. For the type of composition, the method of application is chosen according to the intended purpose and the circumstances prevailing at the time, such as spraying, atomizing, dusting, broadcasting, spreading or watering. The compositions can also contain further auxiliaries, such as stabilizers, defoamers, viscosity regulators, binders or tackifiers, together with fertilizers, micronutrient donors or other formulations for obtaining special effects.

[0490] Suitable carriers and auxiliaries, for example for agricultural use, can be solid or liquid and are substances useful in the art of formulation, such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are described, for example, in WO 1997 / 33890.

[0491] A suspension concentrate is an aqueous formulation in which fine dispersed solid particles of the active compound are suspended. Such formulations contain anti-settling agents and dispersants and can further contain wetting agents to enhance the activity, as well as defoamers and crystal growth inhibitors. In use, these concentrates are diluted in water and are generally applied as sprays to the area to be treated. The amount of the active ingredient can range from 0.5% to 95% of the concentrate.

[0492] Wettable powders are in the form of finely divided particles that are readily dispersible in water or other liquid carriers. These particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin, silica, and other readily wettable organic or inorganic solids. Wettable powders usually contain from 5% to 95% of the active ingredient plus small amounts of wetting agents, dispersants, or emulsifiers.

[0493] Emulsifiable concentrates are homogeneous liquid compositions that are dispersible in water or other liquids and can consist entirely of the active compound with a liquid or solid emulsifier, or may also contain a liquid carrier such as xylene, heavy aromatic naphtha, isophorone, and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquids and are usually applied as a spray to the area to be treated. The amount of active ingredient can range from 0.5% to 95% of the concentrate.

[0494] Granular formulations include both extrudates and coarser granules and are usually applied to the area to be treated without dilution. Typical carriers for granular formulations include sand, fuller's earth, attapulgite clay, bentonite, montmorillonite, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, stucco, wood flour, ground corn cobs, ground peanut hulls, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesium oxide, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate, and other organic or inorganic materials that absorb the active compound or can be coated with the active compound. Granular formulations usually contain 5% to 25% of the active ingredient, which can include surfactants such as heavy aromatic naphtha, kerosene, and other petroleum fractions, or vegetable oils; and / or adhesives such as dextrin, gum, or synthetic resins.

[0495] Dusts are free-flowing mixtures of the active ingredient with finely divided solids such as talc, clay, flour, and other organic and inorganic solids that act as dispersants and carriers.

[0496] Microcapsules are typically droplets or particles of an active ingredient encapsulated within an inert porous shell that permits the enclosed material to escape into the environment at a controlled rate. The diameter of the encapsulated droplets is typically from 1 to 50 microns. The encapsulated liquid typically comprises from 50% to 95% by weight of the capsule and may contain solvents in addition to the active compound. The encapsulated particles are generally porous particles in which a porous membrane seals the particle orifice, retaining the active species in liquid form within the particle pores. The diameter of the particles typically ranges from 1 mm to 1 cm and preferably from 1 mm to 2 mm. The particles are formed by extrusion, aggregation or spheronization, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and carbon grains. The shell or membrane materials include natural and synthetic rubbers, fibrous materials, styrene-butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.

[0497] Other useful formulations for agrochemical applications include simple solutions of the active ingredient in solvents such as acetone, alkylated naphthalenes, xylenes and other organic solvents in which the active ingredient is completely dissolved at the desired concentration. Pressurized sprays may also be used in which the active ingredient is dispersed in a finely divided form due to the evaporation of a low boiling dispersant solvent carrier.

[0498] Suitable agricultural adjuvants and carriers useful for formulating the compositions of the present invention in the above formulation types are well known to those skilled in the art.

[0499] Liquid carriers that can be used include, for example, water, toluene, xylene, naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diglycol rosin acid ester, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol (diproxitol), alkyl pyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexanediol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isopentanone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, stearic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin wax, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropyl alcohol, and higher molecular weight alcohols (such as pentanol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc.), ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone. Water is usually the preferred carrier for diluting the concentrate.

[0500] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite, bleaching earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell powder, and lignin.

[0501] A wide range of surfactants are advantageously employed in the liquid and solid compositions, especially those designed to be diluted with a carrier prior to application. These agents typically comprise from 0.1% to 15% by weight of the formulation when in use. They can be anionic, cationic, non-ionic or polymeric in nature and can be employed as emulsifiers, wetting agents, suspending agents or for other purposes. Typical surfactants include alkyl sulfates such as diethanolammonium lauryl sulfate; alkyl aryl sulfonates such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide adducts such as nonylphenol-C18 ethoxylate; alcohol-alkylene oxide adducts such as tridecanol-C16 ethoxylate; soaps such as sodium stearate; alkylnaphthalenesulfonates such as sodium dibutylnaphthalenesulfonate; salts of dialkyl esters of sulfosuccinic acid such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitan esters such as sorbitan oleate; quaternary amines such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and dialkyl phosphates.

[0502] Other adjuvants commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, defoaming agents, light screening agents, compatibility agents, defoamers, masking agents, neutralizing agents and buffers, corrosion inhibitors, dyes, flavorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.

[0503] In addition, further, other biocidal active ingredients or compositions can be combined with the compositions of the present invention and used in the methods of the present invention and applied simultaneously or sequentially with the compositions of the present invention. When applied simultaneously, these additional active ingredients can be formulated together with the compositions of the present invention or mixed, for example, in a spray tank. These additional biocidal active ingredients can be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and / or plant growth regulators.

[0504] Pesticides mentioned herein by their common names are known, for example, from “The Pesticide Manual”, 15th Edition, British Crop Protection Council 2009.

[0505] In addition, the compositions of the present invention can also be applied together with one or more systemic acquired resistance inducers (“SAR” inducers). SAR inducers are known and described, for example, in U.S. Patent No. US 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.

[0506] Compounds of formula (I) according to the invention are generally used in the form of agrochemical compositions and can be applied to the crop area or plant to be treated simultaneously or sequentially with further compounds. For example, these further compounds can be fertilizers or micronutrient donors or other preparations which influence plant growth. They can also be selective or non-selective herbicides, together with insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or adjuvants which are commonly used in the field of formulation.

[0507] Compounds of formula (I) according to the invention can be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, which compositions comprise as active ingredient at least one compound of formula (I) or at least one preferred individual compound as defined herein (in free form or in agrochemically acceptable salt form) and at least one of the abovementioned adjuvants.

[0508] Accordingly, the invention provides a composition, preferably a fungicidal composition, comprising at least one compound of formula (I) according to the invention, an agriculturally acceptable carrier and optionally an adjuvant. An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use. Agricultural carriers are well known in the art. Preferably, in addition to the compound of formula (I), the composition may further comprise at least one or more pesticidal active compounds, for example further fungicidal active ingredients.

[0509] The compound of formula (I) according to the invention can be the sole active ingredient of the composition, or, where appropriate, it can be mixed with one or more further active ingredients such as pesticidal agents, fungicides, synergists, herbicides or plant growth regulators. In some cases, the further active ingredients can produce an unexpected synergistic activity.

[0510] Examples of suitable additional active ingredients include the following: acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, aniline fungicides, antibiotic fungicides, aromatic fungicides, arsenic-containing fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzoyl aniline fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged biphenyl fungicides, carbamate fungicides, phenylcarbamate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furanamide fungicides, furan aniline fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorus fungicides, organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylthioamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobulurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolo pyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.

[0511] Examples of suitable additional active ingredients include the following: petroleum, 1,1-bis(4-chlorophenyl)-2-ethoxyethanol, 2,4-dichlorophenyl benzenesulfonate, 2-fluoro-N-methyl-N-1-naphthalenacetamide, 4-chlorophenyl phenyl sulfone, acetoprole, aldoxycarb, azadirachtin, carbophenothion, amiton, amiton hydrogen oxalate, amitraz, bromopropylate, arsenic trioxide, azobenzene, azinphos, benomyl, benoxafos, benzyl benzoate, bixafen, brofluthrinate, bromocylen, bromophos, bromopropylate, buprofezin, butocarboxim, butoxycarboxim, butylpyridaben, calcium polysulfide, octachlorostyrene, chlorethoxyfos, carbophenothion, chinomethionat, chlorobenzilate, chlordimeform, chlordimeform hydrochloride, chlorobenzilate, chlorfenson, dicofol, ethyl chlorobenzilate, chloromebuform, chlorfluazuron, chlorpyrifos-methyl, chrysanthemum cinerariifolium I, chrysanthemum cinerariifolium II, chrysanthemum cinerariifolium, clofentezine, coumaphos, crotamiton, crotoxyphos, cyhexatin, cyanofenphos, DCPM, DDT, demeton-S-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methyl sulfone, dichlofluanid, dichlorvos, dicliphos, dicofol, dimefox, dinocap, dinocap-diclexine, dinocap-4, dinocap-6, dinocap-o, nitropentyl, nitrooctyl, nitrobutyl, dichlorvos, diphenyl sulfone, disulfiram, DNOC, dofenapyn, doramectin, dioxathion, eprinomectin, ethion, ethiprole, fenbutatin oxide, fenothiocarb, fenpyrad, fenpyroximate, fenpyrazamine, flumethrin, flufenzine, flubenzimine, flucycloxuron, flufenerim, flubenzimine, FMC 1137, formetanate, formetanate hydrochloride, formparanate, γ-HCH, guazatine, hexythiazox, hexadecyl cyclopropanecarboxylate, isocarbophos, jasmolin I, jasmolin II, iodofenphos, lindane, propargite, mecarbam, dioxathion, methiocarb, methacrifos, methyl bromide, metolcarb, promecarb, moxidectin, naled, 4-chloro-2-(2-chloro-2-methylpropyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one, hexaflumuron, nikkomycin, phenothrin, phenothrin 1:1 zinc chloride complex, omethoate, isoxathion, sulfotep, pp'-DDT, parathion, permethrin, phenthoate, phosalone, phosfolan, phosphamidon, polychloroterpenes, polynactins, propiconazole, pyridaphenthion, propoxur, ethoprophos, pyrazophos, pyrethrins I, pyrethrins II, pyrethrins, pyridaphenthion, pyrimethanil,quinalphos, quintiofos, R-1492, phosalone, rotenone, schradan, cadusafos, selamectin, sulprofos, SSI-121, sulfenuron, sulfluramid, thiotepa, sulfur, flufenzine, tau-fluvalinate, TEPP, bendiocarb, tetradifon, chinomethionat, thiafenox, pirimicarb, thiofanox, methamidophos, crotoxyphos, dimethoate, chlorobenzilate, abamectin, triazophos, triazuron, trichlorfon, triclosan, formetanate, vaniliprole, bethoxazin, copper dioctoate, copper sulfate, cybutryne, dichlone, dichlorophen, humic acid, triphenyltin, slaked lime, sodium thiram, quinoclamine, quinapyramine, simazine, triphenyltin acetate, triphenyltin hydroxide, fosthiazate, piperazine, thiophanate-methyl, chloralose, fenthion, pyridin-4-amine, strychnine, 1-hydroxy-1H-pyridine-2-thione, 4-(quinoxalin-2-ylamino)benzenesulfonamide, 8-hydroxyquinoline sulfate, bronopol, copper hydroxide, cresol, bipyrithione, dodine, sodium phtalimide, formaldehyde, mercaptofen, kasugamycin, kasugamycin hydrochloride hydrate, nickel bis(dimethyldithiocarbamate), 3,5,6-trichloro-2-pyridinol, octhilinone, oxolinic acid, oxytetracycline, potassium hydroxyquinoline sulfate, thiabendazole, streptomycin, streptomycin sesquisulfate, tetrachloroisophthalonitrile, thimerosal, Adoxophyes orana GV, Agrobacterium radiobacter, Amblyseius spp., Autographa gamma NPV, Anagrus atomus, Aphelinus abdominalis, Aphidius colemani, Aphidoletes aphidimyza, Autographa californica NPV, Bacillus sphaericus Neide, Beauveria brongniartii, Chrysoperla carnea, Cryptolaemus montrouzieri, Cydia pomonella GV, Dacnusa sibirica, Diglyphus isaea, Encarsia formosa, Eretmocerus eremicus, Heterorhabditis bacteriophora and H. megidis, Hippodamia convergens, Leptomastix dactylopii,Macrolophus caliginosus, Mamestra brassicae NPV, Metaphycus helvolus, Metarhizium anisopliae var. acridum, Metarhizium anisopliae var. anisopliae, Neodiprion sertifer NPV and Neodiprion lecontei NPV, Orius spp., Paecilomyces fumosoroseus, Phytoseiulus persimilis, Steinernema bibionis, Steinernema carpocapsae, Steinernema feltiae, Steinernema glaseri, Steinernema riobrave, Steinernema riobravis, Steinernema scapterisci, Steinernema spp., Trichogramma spp., Typhlodromus occidentalis, Verticillium lecanii, a pholate, bisazir, busulfan, dimatif, hemel, hempa, metepa, methiotepa, methyl apholate, morzid, penfluron, tepa, thiohempa, thiotepa, tretamine, urethane imine, (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol, (E)-tridec-4-en-1-yl acetate, (E)-6-methylhept-2-en-4-ol, (E,Z)-tetradec-4,10-dien-1-yl acetate, (Z)-dodec-7-en-1-yl acetate, (Z)-hexadec-11-enal, (Z)-hexadec-11-en-1-yl acetate, (Z)-hexadec-13-en-11-yn-1-yl acetate, (Z)-eicos-13-en-10-one, (Z)-tetradec-7-en-1-al, (Z)-tetradec-9-en-1-ol, (Z)-tetradec-9-en-1-yl acetate,(7E,9Z)-dodeca-7,9-dien-1-yl acetate, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate, 14-methyloctadec-1-ene, 4-methylnon-5-ol and 4-methylnon-5-one, α-multistriatin, western pine beetle aggregation pheromone, dodecadienol, geraniol, cuelure, epoxy nonadecane, dodec-8-en-1-yl acetate, dodec-9-en-1-yl acetate, dodec-8,10-dien-1-yl acetate, dominicalure, ethyl 4-methylcaprylate, eugenol, southern pine beetle aggregation pheromone, luremone mixture, luremone mixture I, luremone mixture II, luremone mixture III, luremone mixture IV, hexalure, ipsdienol, phellenol, scarab sex pheromone, trimethyldioxatricyclononane, litlure, pink bollworm sex pheromone, luresal, megatomoic acid, cucumerone, lurexene, octadeca-2,13-dien-1-yl acetate, octadeca-3,13-dien-1-yl acetate, hercon, rhinoceros beetle aggregation pheromone, furecol, lurexan, sordidin, myrmicane, tetradec-11-en-1-yl acetate, Mediterranean fruit fly attractant, Mediterranean fruit fly attractant A, Mediterranean fruit fly attractant B1, Mediterranean fruit fly attractant B2, Mediterranean fruit fly attractant C, trunc-call, 2-(octylthio)ethanol, butopyronoxyl, butoxy(polypropylene glycol), dibutyl adipate, dibutyl phthalate, dibutyl succinate, diethyltoluamide, dimethylcarbate, dimethyl phthalate, ethylhexylglycerin, hexamide, methoquin-butyl, methylneodecanamide, oxamate, picaridin, 1-dichloro-1-nitroethane, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane, 1,2-dichloropropane and 1,3-dichloropropene, 1-bromo-2-chloroethane, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate, 2,2-dichlorovinyl 2-ethylsulfinylethyl methylphosphonate, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate, 2-(2-butoxyethoxy)ethyl thiocyanate, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate, 2-(4-chloro-3,5-dimethylphenoxy)ethanol, 2-chlorovinyl diethyl phosphate, 2-imidazolidinone, 2-isovalerylindane-1,3-dione,2-Methyl(prop-2-ynyl)aminophenylmethylcarbamate, 2-Cyanoethyl laurate, 3-Bromo-1-chloroprop-1-ene, 3-Methyl-1-phenylpyrazol-5-yl dimethylcarbamate, 4-Methyl(prop-2-ynyl)amino-3,5-dimethylphenylmethylcarbamate, 5,5-Dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate, Acephate, Acrylonitrile, Aldrin, Avermectin, Benomyl, Alpha-ecdysone, Aluminium phosphide, Bassa, Neonicotinoid, Athidathion, Methylpyridaphenthion, Bacillus thuringiensis delta-endotoxin, Barium hexafluorosilicate, Barium polysulphide, Bioallethrin, Bayer 22 / 190, Bayer 22408, Beta-cyfluthrate, Beta-cypermethrin, Bioethanomethrin, Bioallethrin, Bis(2-chloroethyl)ether, Borax, Bromfenvinfos, Bromo-DDT, BPMC, Butacarb, Butathiofos, Butonate, Calcium arsenate, Calcium cyanide, Carbon disulphide, Carbon tetrachloride, Cartap hydrochloride, Cevadine, Cinerin I, Chlordane, Chlordecone, Chloroform, Chloropicrin, Cyanofenphos, Chlorprazophos, Cis-resmethrin, Cismethrin, Clocythrin, Cupric acetoarsenite, Cupric arsenate, Cupric oleate, Coumithoate, Cryolite, CS 708, Cyanofenphos, Cyanophos, Cycloprothrin, Cythioate, d-Tetramethrin, DAEP, Dazomet, Decarbofuran, Diamidafos, Isofenphos, Dichlofenthion, Dicresyl, Cyclaniliprole, Dieldrin, Diethyl 5-methylpyrazol-3-yl phosphate, Dilor, Transfluthrin, Dimethacarb, Pyrethrum, Methacrifos, Thiofanox, DSP, Ecdysterone, EI 1642, EMPC, EPBP, Etaphos, Ethiofencarb, Ethyl formate, Ethylene dibromide, Ethylene dichloride, Ethylene oxide, EXD, Fenchlorphos, Ethiofencarb, Fenitrothion, Fenoxacrim, Pyraclofos, Fensulfothion, Ethyl fenthion, Flucofuron, Butylphos, Phosphamidon, Butocarboxim, Furathiocarb, Pyrethrins, Guazatine, Guazatine acetate, Sodium tetrathiocarbonate, Halfenprox, HCH, HEOD, Heptachlor, Phosalone, HHDN, Hydrogen cyanide, Quinomethionate, IPSP, Isazofos, Carbonochlorine, Isodrin, Isofenphos, Imazalil, Isoprothiolane, Oxydemeton-methyl, Juvenile hormone I, Juvenile hormone II, Juvenile hormone III, Chlorprene, Empenthrin, Lead arsenate, Bromophos, Pyridaphenthion,Fosthiazate, Isopropylphenyl methylcarbamate, Magnesium phosphide, Azinphos, Methyl aphidiphos, Pyridaphenthion, Mercurous chloride, Methyloxydemeton, Metam, Metam-potassium, Metam-sodium, Methylsulfonyl fluoride, Butenamiphos, Methoprene, Permethrin, Methoxychlor, Methyl isothiocyanate, Methyl chloroform, Dichloromethane, Indoxacarb, Mirex, Naled, Naphthalene, NC-170, Nicotine, Nicotine sulfate, Nithiazine, Nor-nicotine, O-5-Dichloro-4-iodophenyl O-ethyl ethylthiophosphonate, O,O-Diethyl O-4-methyl-2-oxo-2H-chromen-7-yl thiophosphonate, O,O-Diethyl O-6-methyl-2-propylpyrimidin-4-yl thiophosphonate, O,O,O',O'-Tetrapropyl pyrophosphorodithioate, Oleic acid, p-Dichlorobenzene, Methyl parathion, Pentachlorophenol, Pentachlorophenyl laurate, PH 60-38, Fensulfothion, p-Chlorothion, Phosphine, Phoxim-methyl, Methamidophos, Polychlorodicyclopentadiene isomers, Potassium arsenite, Potassium thiocyanate, Precocene I, Precocene II, Precocene III, Amidapyrimiphos, Profluthrin, Promecarb, Prothiofos, Pyrazophos, Transfluthrin, Quassia extract, Quinalphos-methyl, Chlorthiophos, Iodochlorhydroxyquin, Rotenone, Tiamethrin, Ryanodine, Ryanodine, Sabadilla, Schradan, Nemacur, SI-0009, Thiophenecarbonitrile, Sodium arsenite, Sodium cyanide, Sodium fluoride, Sodium hexafluorosilicate, Sodium pentachlorophenate, Sodium selenate, Sodium thiocyanate, Sulcofuron, Sulcofuron-sodium, Sulfuryl fluoride, Sulfinophos, Tar, Pirimicarb, TDE, Butylpyrimiphos, Abate, Esbiothrin, 1,1,2,2-Tetrachloroethane, Thichlorofos, Thiosultap, Thiosultap oxalate, Ethoprophos, Thiosultap monosodium, Tefluthrin, Transfluthrin, Triazamate, Trichlormetaphos-3, Trifenmorph, Promecarb, Tolprocarb, Picoxystrobin, Methoprene, Veratridine, Veratrine, XMC, Zetamethrin, Zinc phosphide, Etoxazole, Ethofenprox, Tetramethrin, Bis(tributyltin) oxide, Bromoacetamide, Iron phosphate, Niclosamide-ethanolamine, Tributyltin oxide, Pyrimorph, Melanoplus, 1,2-Dibromo-3-chloropropane, 1,3-Dichloropropene, 3,4-Dichlorotetrahydrothiophene 1,1-dioxide, 3-(4-Chlorophenyl)-5-methylrhodanine, 5-Methyl-6-thioxo-1,3,5-thiadiazinan-3-yl acetic acid, 6-Isopentenylaminopurine, Anisiflupurin, Benclothiaz, Cytokinin, DCIP, Furfural, Isamidofos, Kinetin, Myrothecium verrucaria composition, Tetrachlorothiophene, Xylenol, Zeatin, Potassium ethylxanthate, Benzoic acid, Benzoic acid S-methyl,Extract of Reynoutria sachalinensis, α-chloroalcohol, warfarin, barium carbonate, diphacinone, bromadiolone, brodifacoum, bromethalin, chlorophacinone, cholecalciferol, coumatetralyl, coumafuryl, pyriminil, difenacoum, thiacoumone, diphacin, calciferol, flocoumafen, fluoroacetamide, fluradone, fluradone hydrochloride, volex, phosazetim, phosphorus, pival, pyridiminol, scilliroside, sodium fluoroacetate, thallium sulfate, warfarin, 2-(2-butoxyethoxy)ethyl piperate, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone, farnesol with nerolidol, piperonyl butoxide, MGK 264, piperonyl butoxide, piperonal butoxide, synergistic ester (propyl isomer), S421, synergistic powder, sesasmolin, sulfoxide, anthraquinone, copper naphthenate, copper oxychloride, dicyclopentadiene, silafluofen, zinc naphthenate, ziram, emarimicin, ribavirin, indoleacetic hydrazide, mercuric oxide, thiophanate-methyl, azaconazole, bitertanol, bixafen, cyproconazole, difenoconazole, epoxiconazole, fluquinconazole, flusilazole, flutriafol, furametpyr, hexaconazole, imazalil, imibenconazole, ipconazole, metconazole, metominostrobin, penconazole, prothioconazole, pyrifenox, prochloraz, propiconazole, pyridinitril, simeconazole, tebuconazole, fluoxastrobin, triadimefon, triadimenol, triflumizole, triticonazole, ancymidol, fenarimol, fluoroimide, bupirimate, dimethirimol, ethirimol, dodemorph, fenpropidin, fenpropimorph, spiroxamine, tridemorph, cyprodinil, cymoxanil, pyrimethanil; fenpiclonil, fludioxonil, metalaxyl, furalaxyl, metalaxyl, R-metalaxyl; ofurace, oxadixyl, carbendazim, debacarb, tecnazene, thiabendazole, chlozolinate, dichlozoline, myclozoline, procymidone, vinclozoline, boscalid, carboxin, furcarbanil, flutolanil, mepronil, oxycarboxin, penthiopyrad, thifluzamide, dodine, guazatine, azoxystrobin, enestrobin, enestroburin, enoxamyl, fluoxastrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraoxystrobin, pyraclostrobin, ferbam, mancozeb, maneb,Metiram, zinc methyldithiocarbamate, zinc dithiocarbamate, captafol, captan, isoxaben, folpet, tolclofos-methyl, Bordeaux mixture, copper oxide, mancozeb, oxine-copper, phthalide, kitazin-p, iprobenfos, chlorpyrifos-methyl, tolclofos-methyl, anilazine, benthiavalicarb, blasticidin-S, chloroneb, chlorothalonil, cyflufenamid, cymoxanil, cyclobutrifluram, diclocymet, diclomezine, dicloran, diethofencarb, dimethomorph, flumorph, dithianon, ethaboxam, etridiazole, fenamidone, fenoxanil, ferimzone, fluazinam, flumetylsulforim, fluopicolide, fluoxytioconazole, flusulfamide, fluxapyroxad, fenhexamid, fosetylaluminium, hymexazol, propineb, cyazofamid, methasulfocarb, metrafenone, pencycuron, phthalide, polyoxins, propamocarb, pyrimethanil, proquinazid, pyroquilon, pyriofenone, quinoxyfen, quintozene, tiadinil, triazoxide, tricyclazole, triforine, validamycin, valifenalate, zoxamide, mandipropamid, flubeneteram, isopyrazam, sedaxane, benzovindiflupyr, fluxametamide, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (3’,4’,5’-trifluoro-biphenyl-2-yl)-amide, isoflucypram, isofetamid, dipymetitrone, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithieno[1,2-c]isothiazole-3-carbonitrile, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide, 4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine-3-carbonitrile,(R)-3-(Difluoromethyl)-1-methyl-N-[1,1,3-trimethylinden-4-yl]pyrazole-4-carboxamide, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-2,5-dimethylpyrazol-3-amine, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, fluindapyr, jiaxiangjunzhi, lvbenmixianan, dichlobentiazox, mandestrobin, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone, 2-[2-fluoro-6-[(8-fluoro-2-methylquinolin-3-yl)oxy]phenyl]propan-2-ol, oxathiapiprolin, N-[6-[[[(1-methyltetrazol-5-yl)phenylmethylene]amino]oxymethyl]-2-pyridinyl]carbamic acid tert-butyl ester, pyraziflumid, inpyrfluxam, trolprocarb, trifloxystrobin, ipfentrifluconazole, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethylinden-4-yl]pyridine-3-carboxamide, N'-(2,5-dimethyl-4-phenoxyphenyl)-N-ethyl-N-methylformamidine, N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chlorophenyl]methanesulfonate, N-[6-[[(Z)-[(1-methyltetrazol-5-yl)phenylmethylene]amino]oxymethyl]-2-pyridinyl]carbamic acid but-3-ynyl ester, N-[[5-[4-(2,4-dimethylphenyl)-1,2,4-triazol-3-yl]-2-methylphenyl]methyl]carbamic acid methyl ester, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine, pyridachlometyl, 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylinden-4-yl]pyrazole-4-carboxamide, 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methylphenyl]-4-methyl-1H-tetrazol-5-one, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]-1H-tetrazol-5-one,Aminopyrifen, amisulbrom, indaziflam, sedaxane, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yloxy]-2-methoxyimino-N,3-dimethyl-pent-3-enamide, florylpicoxamid, fenpicoxamid, metarylpicoxamid, tebufloquin, ipflufenoquin, quinofumelin, isofetamid, ethyl 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolan-2-yl]methoxy]phenyl]methyl]pyrazole-3-carboxylate (which can be prepared by the method described in WO 2020 / 056090), ethyl 1-[[4-[(Z)-2-ethoxy-3,3,3-trifluoro-prop-1-enoxy]phenyl]methyl]pyrazole-3-carboxylate (which can be prepared by the method described in WO 2020 / 056090), methyl N-[[4-[1-(4-cyclopropyl-2,6-difluoro-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate (which can be prepared by the method described in WO 2020 / 097012), methyl N-[[4-[1-(2,6-difluoro-4-isopropyl-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate (which can be prepared by the method described in WO 2020 / 097012), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-N-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (which can be prepared by the method described in WO 2020 / 109391), 6-chloro-N-[2-(2-chloro-4-methyl-phenyl)-2,2-difluoro-ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide (which can be prepared by the method described in WO 2020 / 109391), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)-N-[2-(3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (which can be prepared by the method described in WO 2020 / 109391), N-[2-[2,4-dichlorophenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide, N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide, benzothiazole ester, phenamacril, zinc 5-amino-1,3,4-thiadiazole-2-thiolate (2:1), fluopyram, flufenoxadiazam, fluopyramide, fluopyram + TX,Pyrapropoyne, picarbutrazox, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)nicotinamide, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindan-4-yl)nicotinamide, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile, metyltetraprole, α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl]-5-pyrimidine methanol, fluoxapiprolin, enoxastrobin, methyl (Z)-3-methoxy-2-[2-methyl-5-[4-(trifluoromethyl)-1,2,4-triazol-2-yl]phenoxy]prop-2-enoate, methyl (Z)-3-methoxy-2-[2-methyl-5-(4-propyl-1,2,4-triazol-2-yl)phenoxy]prop-2-enoate, methyl (Z)-2-[5-(3-isopropyl-1H-pyrazol-1-yl)-2-methylphenoxy]-3-methoxyprop-2-enoate, methyl (Z)-3-methoxy-2-[2-methyl-5-(3-propyl-1H-pyrazol-1-yl)phenoxy]prop-2-enoate, methyl (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy]prop-2-enoate (these compounds can be prepared by the methods described in WO 2020 / 079111), methyl (Z)-2-(5-cyclohexyl-2-methylphenoxy)-3-methoxyprop-2-enoate, methyl (Z)-2-(5-cyclopentyl-2-methylphenoxy)-3-methoxyprop-2-enoate (these compounds can be prepared by the methods described in WO 2020 / 193387), 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile, trinexapac-ethyl, pyraoxystrobin, zhongshengmycin, thiodiazole copper, thiazole zinc, amitrole, iprodione, 2-(2,4-dichlorophenyl)-4,5-dihydro-4-(1-methylethyl)-5-oxo-1H-imidazole-1-carboxaldehyde O-(2,4-dinitrophenyl)oxime, N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxyethoxy]-3-pyridinyl]-N-ethyl-N-methylformamidine,N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-isopropyl-N-methyl-formamidine (these compounds can be prepared by the methods described in WO 2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine (this compound can be prepared by the methods described in IPCOM000249876D); N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine, N'-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine (these compounds can be prepared by the methods described in WO 2018 / 228896); N-ethyl-N'-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine, N-ethyl-N'-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine (these compounds can be prepared by the methods described in WO 2019 / 110427); N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide, 8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide, 8-fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide,N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, N-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide, N-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide (these compounds can be prepared by the methods described in WO 2017 / 153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline, 4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline (these compounds can be prepared by the methods described in WO 2017 / 025510); 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline, 3-(4,4-difluoro-3,3-dimethyl-1-isoquinolinyl)-7,8-dihydro-6H-cyclopenta[d]benzimidazole (these compounds can be prepared by the methods described in WO 2016 / 156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, 3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide,4,4-Dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, ethyl 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate, N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine (these compounds can be prepared by the methods described in WO 2017 / 055473, WO 2017 / 055469, WO 2017 / 093348 and WO 2017 / 118689); 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (this compound can be prepared by the method described in WO 2017 / 029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (this compound can be prepared by the method described in WO 2017 / 029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxypropyl]imidazole-4-carbonitrile (this compound can be prepared by the method described in WO 2016 / 156290); 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluorophenyl)-2-hydroxypropyl]imidazole-4-carbonitrile (this compound can be prepared by the method described in WO 2016 / 156290); (4-phenoxyphenyl)methyl 2-aminopyridine-3-carboxylate (this compound can be prepared by the method described in WO 2014 / 006945); 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone (this compound can be prepared by the method described in WO 2011 / 138281),N-Methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide; N-Methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine (this compound can be prepared by the method described in WO 2018 / 153707); N'-(2-chloro-5-methyl-4-phenoxyphenyl)-N-ethyl-N-methyl-formamidine; N'-[2-chloro-4-(2-fluorophenoxy)-5-methylphenyl]-N-ethyl-N-methyl-formamidine (this compound can be prepared by the method described in WO 2016 / 202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide (this compound can be prepared by the method described in WO 2014 / 095675); (5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone, (3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone (these compounds can be prepared by the method described in WO 2017 / 220485); 2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide (this compound can be prepared by the method described in WO 2018 / 065414); ethyl 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylate (this compound can be prepared by the method described in WO 2018 / 158365); 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide, N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, N-[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, N-[N-methoxy-methyl-carbimino]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (these compounds can be prepared by the method described in WO 2018 / 202428).

[0512] The compounds of the present invention can also be used in combination with anthelmintic agents. Such anthelmintic agents include compounds selected from macrolide compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin, and milbemycin derivatives as described in EP 0357460, EP 0444964, and EP 0594291. Additional anthelmintic agents include semi-synthetic and biosynthetic avermectin / milbemycin derivatives such as those described in US 5,015,630, WO 9415944, and WO 9522552. Additional anthelmintic agents include benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of this class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel, or morantel. Additional anthelmintic agents include trematocides (such as triclabendazole and closantel) and cestocides (such as praziquantel and etisazole).

[0513] The compounds of the present invention can be used in combination with derivatives and analogs of paraherquamide / marcfortine anthelmintic agents and antiparasitic oxazolines (such as those disclosed in US 5478855, US 4639771, and DE-19520936).

[0514] The compounds of the present invention can be used in combination with derivatives and analogs of general classes of dioxolane antiparasitic agents as described in WO 9615121 and also with cyclic depsipeptides having anthelmintic activity (such as those described in WO 9611945, WO 9319053, WO9325543, EP 0626375, EP 0382173, WO 9419334, EP 0382173, and EP 0503538).

[0515] The compounds of the present invention can be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as chlorfenapyr; ecdysone agonists such as tebufenozide, etc.; neonicotinoids such as imidacloprid, etc.

[0516] The compounds of the present invention can be used in combination with terpenoid alkaloids such as those described in WO 95 / 19363 or WO 04 / 72086, especially the compounds disclosed therein.

[0517] Other examples of such bioactive compounds that can be used in combination with the compounds of the present invention include, but are not limited to, the following:

[0518] Organophosphates: Acephate, Azamethiphos, Azinphos-ethyl, Azinphos-methyl, Bromophos, Bromophos-ethyl, Cadusafos, Chlorethoxyphos, Chlorpyrifos, Chlorfenphos, Chloromethylphos, Demeton, Demeton-S-methyl, Demeton-S-methyl sulfone, Chlorphoxim, Diazinon, Dichlorvos, Naled, Dimethoate, Disulfoton, Ethoprophos, Etrimfos, Famphur, Fenamiphos, Fenthion, Flupyrazofos, Fonofos, Formothion, Fosthiazate, Heptenophos, Isazofos, Isopropylphosphoramidothioate, Isoxathion, Malathion, Methacrifos, Methamidophos, Methidathion, Methyl parathion, Oxamyl, Phosphamidon, Phosmet, Phosfolan, Pirimiphos-methyl, Profenofos, Prothiofos, Proetamphos, Prothiophos, Pyraclofos, Pyridaphenthion, Quinalphos, Sulfotep, Tebupirimfos, Tefluthrin, Temephos, Terbufos, Tetrachlorvinphos, Thiodicarb, Triazophos, Trichlorfon, Trimethacarb.

[0519] Carbamates: Aldicarb, Aldoxycarb, Benfuracarb, Butocarboxim, Carbaryl, Carbofuran, Carbosulfan, Cloethocarb, Ethiofencarb, Fenoxycarb, Fensulfothion, Formetanate, Isoprocarb, Indoxacarb, Methiocarb, Methomyl, 5-Methyl-m-isopropylphenyl butynyl (methyl) carbamate, Oxamyl, Pirimicarb, Propoxur, Thiodicarb, Trimethacarb, UC-51717.

[0520] Pyrethroids: Acrinathrin, Allethrin, Alphamethrin, 5-Benzyl-3-furylmethyl (E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidene methyl) cyclopropanecarboxylate, Bifenthrin, Beta-cyfluthrin, Cyfluthrin, Alpha-cypermethrin, Beta-cypermethrin, Bioallethrin, Bioallethrin ((S)-cyclopentyl isomer), Bioresmethrin, Bifenthrin, NCI-85193, Pyrethroid, Cyhalothrin, Cypermethrin, Cyanobenzilate, Deltamethrin, Empenthrin, Esfenvalerate, Etofenprox, Fluvalinate, Flucythrinate, Flufenprox, Flumethrin, Imiprothrin, Lambda-cyhalothrin, Permethrin, Phenothrin, Propargite, Pyrethrum (natural product), Resmethrin, Tetramethrin, Theta-cypermethrin, Silfenin, Tefluthrin, Tefluthrin, Tebufenpyrad, Tetramethrin, Zeta-cypermethrin.

[0521] Arthropod growth regulators: a) Chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, flucarazone, flufenoxuron, flubendiamide, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, ethofenprox, hexythiazox, etoxazole, clofentezine; b) Ecdysteroid antagonists: halofenozide, methoxyfenozide, tebufenozide; c) Juvenile hormone analogs: pyriproxyfen, methoprene (including S-methoprene), phenoxycarb; d) Lipid biosynthesis inhibitors: spirodiclofen.

[0522] Other antiparasitic agents: acequinocyl, amitraz, AKD-1022, ANS-118, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorbenside, chlordimeform, chlorfenapyr, chromafenozide, clothianidin, cyanaguanide, diacloden, diafenthiuron, DBI-3204, diomycin, dihydroxymethyl dihydroxypyrrolidine, dicofol, dienochlor, endosulfan, ethiprole, etofenprox, fenazaquin, flumite, MTI-800, flubendazole, flufenpyr-ethyl, flufenerim, flumethrin, flutriafol, halofenprox, hydramethylnon, IKI-220, hydrozincite, NC-196, neem guard, nidinorterfuran, nitenpyram, SD-35651, WL-108477, pyridalyl, propargite, protrifenbute, pymetrozine, pyridaben, pyrimidifen, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen, silomadine, spinosad, pyridaben, tetradifon, tetramycin, thiacloprid, thiosultap, thiamethoxam, tolfenpyrad, triazamate, triacetoxyscirpenol, verbutin, vertalec, YI-5301.

[0523] Biological agents: Bacillus thuringiensis ssp. aizawai, Bacillus thuringiensis ssp. kurstaki, Bacillus thuringiensis delta-endotoxin, baculoviruses, entomopathogenic bacteria, viruses and fungi.

[0524] Bactericides: chlortetracycline, oxytetracycline, streptomycin.

[0525] Other biological agents: enrofloxacin, febantel, penethamate hydriodide, meloxicam, cephalexin, kanamycin, pimobendan, clenbuterol, omeprazole, thiomurin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiofur, carprofen, mefronil, praziquantel, triclabendazole.

[0526] The following mixtures of compounds of formula (I) with active ingredients are preferred. The abbreviation "TX" means a compound selected from the compounds of formula (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-A5), (I-B), (I-C), or (I-D), or a compound selected from the compounds listed in Tables A-1 to A-26 or the compounds listed in Table P (below), and compounds selected from the group consisting of: petroleum + TX, 1,1-bis(4-chlorophenyl)-2-ethoxyethanol + TX, 2,4-dichlorophenyl benzenesulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenyl phenyl sulfone + TX, acetoprole + TX, aldicarb + TX, cyhexatin + TX, bromopropylate + TX, amiton + TX, amiton hydrogen oxalate + TX, amitraz + TX, chlorbenside + TX, arsenic trioxide + TX, azobenzene + TX, azinphos + TX, benomyl + TX, benoxafos + TX, benzyl benzoate + TX, boscalid + TX, bromfenvinphos + TX, bromocyclen + TX, bromophos + TX, bromopropylate + TX, buprofezin + TX, butocarboxim + TX, butoxycarboxim + TX, butylpyridaben + TX, calcium polysulfide + TX, camphechlor + TX, carbaryl + TX, carbophenothion + TX, chlobenzthiazone + TX, chinomethionat + TX, chlordimeform + TX, chlordimeform hydrochloride + TX, chlorobenzilate + TX, chlorfenson + TX, chloropropylate + TX, chlorothiophos + TX, cinerin I + TX, cinerin II + TX, cinerin + TX, chlorthiophos + TX, coumaphos + TX, crotamiton + TX, crotoxyphos + TX, cycloheximide + TX, DCPM + TX, DDT + TX, demeton-S-methyl + TX, demeton-S-methyl-O + TX, demeton-S-methyl-S + TX, demeton-S-methylsulfon + TX, dichlofluanid + TX, dichlorvos + TX, dicliphos + TX, dienochlor + TX, dimefox + TX, dinocap + TX, dinocap-diclexine + TX, dinocap-4 + TX, dinocap-6 + TX, dinocap-o + TX, dinopenton + TX, dinosulfon + TX, dinoseb + TX, disulfoton + TX, diphenyl sulfone + TX, disulfiram + TX, DNOC + TX,Dofenapyn + TX, Doramectin + TX, Ciodrin + TX, Eprinomectin + TX, Ethion + TX, Etrimfos + TX, Amitraz + TX, Fenbutatin Oxide + TX, Bendiocarb + TX, Fenpyrad + TX, Fenpyroximate + TX, Fluopyram + TX, Binapacryl + TX, Fentrifanil + TX, Flufenerim + TX, Flucycloxuron + TX, Fluhexafon + TX, Fluvalinate + TX, FMC 1137 + TX, Formetanate + TX, Formetanate Hydrochloride + TX, Formparanate + TX, γ-HCH, Chloranil + TX, Bifenazate + TX, Hexadecyl Cyclopropanecarboxylate + TX, Isocarbophos + TX, Pyrethrins I + TX, Pyrethrins II + TX, Iodofenphos + TX, Lindane + TX, Propargite + TX, Aphidiphos + TX, Disulfoton + TX, Methiophanate + TX, Methacrifos + TX, Methyl Bromide + TX, MTMC + TX, Carbamyl + TX, Milbemycin + TX, Propetamphos + TX, Monocrotophos + TX, Phenthoate + TX, Moxidectin + TX, Naled + TX, 4-Chloro-2-(2-chloro-2-methylpropyl)-5-[(6-iodopyridin-3-yl)methoxy]pyridazin-3-one + TX, Flucythrinate + TX, Nikkomycin + TX, Phosalone + TX, Phosalone 1:1 Zinc Chloride Complex + TX, Omethoate + TX, Isoxathion + TX, Sulfotep + TX, pp'-DDT, Parathion, Permethrin, Phenkapton, Phosalone, Phosfolan, Phosphamidon, Polychloroterpenes, Polynactins, Proclonol, Pyridaphenthion, Propoxur, Ethoprophos, Prothiofos, Pyrethrins I, Pyrethrins II, Pyrethrins, Pyridaphenthion, Pyrimiphos, Quinalphos, Quintiofos, R-1492, Glyphosate, Rotenone, Schradan, Nemacur, Selamectin, Sulfotep, SSI-121, Sufentanil, Flufenoxuron, Tau-Fluvalinate, TEPP, Tertbutylcarb, Tetradifon, Tebupirimfos, Thiafenox, Thiodicarb, Thiofanox, Thiodicarb, Trimethacarb, Methyldisulfoton, Chlorobenzilate, Thuringiensin, Triazophos, Triazuron, Trichlorfon, Trivermectin, OxamylVaniliprole + TX, Bethoxazin + TX, Copper dicaprylate + TX, Copper sulfate + TX, Cybutryne + TX, Dichlone + TX, Dichlorophen + TX, Indole-3-acetic acid + TX, Triphenyltin + TX, Slaked lime + TX, Sodium thiram + TX, Mexacarbate + TX, Quinonamid + TX, Simazine + TX, Triphenyltin acetate + TX, Triphenyltin hydroxide + TX, Crufomate + TX, Piperazine + TX, Thiophanate + TX, Chloralose + TX, Fenthion + TX, Pyridin-4-amine + TX, Strychnine + TX, 1-Hydroxy-1H-pyridine-2-thione + TX, 4-(Quinoxalin-2-ylamino)benzenesulfonamide + TX, 8-Hydroxyquinoline sulfate + TX, Bronopol + TX, Cupric hydroxide + TX, Cresol + TX, Bispyrithione + TX, Dodecylguanidine acetate + TX, Sodium dimehypo + TX, Formaldehyde + TX, Mercuricaphen + TX, Kasugamycin + TX, Kasugamycin hydrochloride hydrate + TX, Nickel bis(dimethyldithiocarbamate) + TX, 3,5,6-Trichloro-2-pyridinol + TX, Octhilinone + TX, Oxolinic acid + TX, Oxytetracycline + TX, Potassium 8-hydroxyquinoline sulfate + TX, Thiabendazole + TX, Streptomycin + TX, Streptomycin sesquisulfate + TX, Tebufenozide + TX, Thimerosal + TX, Adoxophyes orana granulovirus + TX, Agrobacterium radiobacter + TX, Amblyseius spp. + TX, Autographa gamma nuclear polyhedrosis virus + TX, Anagrus atomus + TX, Aphelinus abdominalis + TX, Aphidius colemani + TX, Aphidoletes aphidimyza + TX, Autographa californica nuclear polyhedrosis virus + TX, Bacillus sphaericus Neide + TX, Beauveria brongniartii + TX, Chrysoperla carnea + TX, Cryptolaemus montrouzieri + TX, Cydia pomonella granulovirus + TX, Dacnusa sibirica + TX, Diglyphus isaea + TX, Encarsia formosa + TX, Eretmocerus eremicus + TX, Heterorhabditis bacteriophora and Heterorhabditis megidis + TX, Hippodamia convergens + TX,Leptomastix dactylopii + TX, Macrolophus caliginosus + TX, Mamestra brassicae NPV + TX, Metaphycus helvolus + TX, Metarhizium anisopliae var. acridum + TX, Metarhizium anisopliae var. anisopliae + TX, Neodiprion sertifer NPV and Neodiprion lecontei NPV + TX, Orius spp., Paecilomyces fumosoroseus + TX, Phytoseiulus persimilis + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Trichogramma spp., Typhlodromus occidentalis + TX, Verticillium lecanii + TX, apholate, bisazir, busulfan, dimatif, hemel, hempa, metepa, methiotepa, methyl apholate, morzid, penfluron, tepa, thiohempa, thiotepa, tretamine, urethaneimine, (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol, (E)-tridec-4-en-1-yl acetate, (E)-6-methylhept-2-en-4-ol, (E,Z)-tetradec-4,10-dien-1-yl acetate(Z)-Dodec-7-en-1-yl acetate + TX, (Z)-Hexadec-11-enal + TX, (Z)-Hexadec-11-en-1-yl acetate + TX, (Z)-Hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-Eicos-13-en-10-one + TX, (Z)-Tetradec-7-en-1-al + TX, (Z)-Tetradec-9-en-1-ol + TX, (Z)-Tetradec-9-en-1-yl acetate + TX, (7E,9Z)-Dodec-7,9-dien-1-yl acetate + TX, (9Z,11E)-Tetradec-9,11-dien-1-yl acetate + TX, (9Z,12E)-Tetradec-9,12-dien-1-yl acetate + TX, 14-Methyloctadec-1-ene + TX, 4-Methylnon-5-ol and 4-Methylnon-5-one + TX, α-Multistriatin + TX, Western pine beetle aggregation pheromone + TX, Dodecadienol + TX, Gossyplure + TX, Cuelure + TX, Epoxynonadecane + TX, Dodec-8-en-1-yl acetate + TX, Dodec-9-en-1-yl acetate + TX, Dodec-8,10-dien-1-yl acetate + TX, Dominicalure + TX, Ethyl 4-methylcaprylate + TX, Eugenol + TX, Southern pine beetle aggregation pheromone + TX, Medlure mixture + TX, Medlure mixture I + TX, Medlure mixture II + TX, Medlure mixture III + TX, Medlure mixture IV + TX, Hexalure + TX, Ipsdienol + TX, Scolytol + TX, Japanese beetle sex pheromone + TX, Trimethyldioxatricyclononane + TX, Litlure + TX, Pink bollworm sex pheromone + TX, Medlure + TX, Megatomoic acid + TX, Cuelure + TX, Muscalure + TX, Octadec-2,13-dien-1-yl acetate + TX, Octadec-3,13-dien-1-yl acetate + TX, Hercon Pherocon + TX, Coconuts rhinoceros beetle aggregation pheromone + TX, Fyfanon + TX, Cidial + TX, Soldiure + TX, Mycophila pheromone + TX, Tetradec-11-en-1-yl acetate + TX, Mediterranean fruit fly attractant + TX, Mediterranean fruit fly attractant A + TX, Mediterranean fruit fly attractant B1 + TX, Mediterranean fruit fly attractant B2 + TX, Mediterranean fruit fly attractant C + TX, Trunc-call + TX, 2-(Octylthio)ethanol + TX, Butopyronoxyl + TX, Butoxy(polypropylene glycol) + TX, Dibutyl adipate + TX, Dibutyl phthalate + TX, Dibutyl succinate + TX, Diethyltoluamide + TX, Dimethyl carbate + TX, Dimethyl phthalate + TX, 2-Ethylhexyl diol + TX, Hexamide + TX,methoquin-butyl + TX, methylneodecanamide + TX, oxamate + TX, picaridin + TX, 1,1-dichloro-1-nitroethane + TX, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane + TX, 1,2-dichloropropane and 1,3-dichloropropene + TX, 1-bromo-2-chloroethane + TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate + TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methylphosphonate + TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate + TX, 2-(2-butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyl diethyl phosphate + TX, 2-imidazolidinone + TX, 2-isovalerylindane-1,3-dione + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate + TX, 2-cyanothioethyl laurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate + TX, 5,5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate + TX, acephate + TX, acrylonitrile + TX, aldrin + TX, alomycin + TX, allyxycarb + TX, α-exotoxin + TX, aluminium phosphide + TX, aminocarb + TX, neonicotinoid + TX, athidathion + TX, pirimiphos-methyl + TX, Bacillus thuringiensis δ-endotoxin + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, chrysanthemum cinerariifolium + TX, Bayer 22 / 190 + TX, Bayer 22408 + TX, beta-cyfluthrin + TX, beta-cypermethrin + TX, bioethanomethrin + TX, bioallethrin + TX, bis(2-chloroethyl) ether + TX, borax + TX, bromfenvinfos + TX, bromo-DDT + TX, dimecarb + TX, chlorthiophos + TX, butathiofos + TX, butonate + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, cartap hydrochloride + TX, cevadine + TX, endosulfan + TX, chlordane + TX, kepone + TX, chloroform + TX, chloropicrin + TX, cyanofenphos + TX, chlorprazophos + TX, cis-resmethrin + TX, cismethrin + TXClocythrin (alias) + TX, Cupric acetoarsenite + TX, Cupric arsenate + TX, Cupric oleate + TX, Coumithoate + TX, Cryolite + TX, CS 708 + TX, Cyanofenphos + TX, Cyanophos + TX, Cycloprothrin + TX, Cythioate + TX, d-Amtid + TX, DAEP + TX, Dazomet + TX, Decarbofuran + TX, Diamidafos + TX, EPN + TX, Dichlofenthion + TX, Dicresyl + TX, Cyclaniliprole + TX, Dieldrin + TX, Diethyl 5-methylpyrazol-3-yl phosphate + TX, Dilor + TX, Transfluthrin + TX, Dimethiocarb + TX, Pyrethrin II + TX, Methyldichlorvos + TX, Dimetilan + TX, Binapacryl + TX, Pentachloronitrobenzene + TX, Nitrophen + TX, Phenthoate + TX, Tetramethrin + TX, DSP + TX, Ecdysterone + TX, EI1642 + TX, EMPC + TX, EPBP + TX, Etaphos + TX, Ethiofencarb + TX, Ethyl formate + TX, Ethylene dibromide + TX, Ethylene dichloride + TX, Ethylene oxide + TX, EXD + TX, Fenchlorphos + TX, Etofenprocarb + TX, Fenitrothion + TX, Fenoxacrim + TX, Pyrethroid + TX, Fensulfothion + TX, Ethyl fenthion + TX, Flucofuron + TX, Butathiofos + TX, Phosphamidon + TX, Butocarboxim + TX, Furathiocarb + TX, Pyrethrum + TX, Guazatine + TX, Guazatine acetate + TX, Sodium tetrathiocarbonate + TX, Halfenprox + TX, HCH + TX, HEOD + TX, Heptachlor + TX, Hostaquick + TX, HHDN + TX, Hydrogen cyanide + TX, Quinomethionate + TX, IPSP + TX, Isazofos + TX, Carbonochlorid + TX, Isodrin + TX, Isofenphos + TX, Imazalil + TX, Isoprothiolane + TX, Oxydemeton-methyl + TX, Juvenile hormone I + TX, Juvenile hormone II + TX, Juvenile hormone III + TX, Chlorcyclohexane + TX, Methyl 2,4-dienylcyclopropanecarboxylate + TX, Lead arsenate + TX, Bromfenvinfos + TX, Acetamiprid + TX, Tiazofos + TX, m-Isopropylphenyl methylcarbamate + TX, Magnesium phosphide + TX, Azinphos + TX, Metasystox-R + TX, Oxydemeton-methyl + TX, Mercurous chloride + TX, Methanesulfinylphosphoryl chloride + TX, Metam + TX, Metam potassium + TX, Metam sodium + TX, Methylsulfonyl fluoride + TX, Butamifos + TX, Methoprene + TX, Permethrin + TX, Methoxychlor + TX, Methyl isothiocyanate + TX, Methyl chloroform + TX, Methylene chloride + TX, Oxythioquinox + TX, Mirex + TX, Naled + TX, Naphthalene + TX, NC-170 + TX, Nicotine + TX,Nicotine sulfate + TX, nithiazine + TX, orthonicotine + TX, O-5-dichloro-4-iodophenyl O-ethylethyl phosphonothioate + TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl phosphonothioate + TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphonothioate + TX, O,O,O',O'-tetrapropyl dithiodipyrophosphate + TX, oleic acid + TX, p-dichlorobenzene + TX, methyl parathion + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, PH 60-38+TX, fenthion+TX, parathion+TX, phosphine+TX, methyl phoxim+TX, methamidophos+TX, polychlorinated dicyclopentadiene isomers+TX, potassium arsenite+TX, potassium thiocyanate+TX, precocious element I+TX, precocious element II+TX, precocious element III+TX, amidophos+TX, profluthrin+TX, fenthion+TX, pyraclostrobin+TX, anti-pyrethroid+TX, quassia extract+TX, quinalphos-methyl+TX, oxazolidinone+TX, iodophos-amide+TX, resmethrin+TX TX, rotenone + TX, thiamethoxam + TX, ryanodine + TX, sabadilla + TX, octamethoxazole + TX, clostridium + TX, SI-0009 + TX, thiamethoxam + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium hexafluorosilicate + TX, sodium pentachlorophenol + TX, sodium selenate + TX, sodium thiocyanate + TX, sulcofuron + TX, sulcofuron-sodium + TX, sulfuryl fluoride + TX, thiopropion + TX, tar + TX, thiamethoxam + TX, TDE + TX, butylpyrimidinphos + TX, dimethophos + TX, cyclopentyl thiocarb + TX, tetrachloroethane + TX, thiochlorvos + TX, cyclohexane + TX, cyclohexane oxalate + TX, cypermethrin + TX, cypermethrin sodium + TX, tetrabromothrin + TX, permethrin + TX, trichlormetaphos-3 + TX, chlorpyrifos + TX, chlorpyrifos + TX, trichlormetaphos-3 + TX, chlorpyrifos + TX, Methoprene + TX, Veratridine + TX, Veratridine + TX, XMC + TX, Zetamethrin + TX, Zinc phosphide + TX, Tolfenphos + TX, and Cypermethrin + TX, Cypermethrin + TX, Bis(tributyltin) oxide + TX, Bromoacetamide + TX, Ferric phosphate + TX, Niclosamide-ethanolamine + TX, Tributyltin oxide + TX, Pyrroline + TX, Snail killer + TX, 1,2-dibromo-3-chloropropane + TX, 1,3-dichloropropylene + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide + TX,3-(4-Chlorophenyl)-5-methylrhodanine + TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid + TX, 6-isopentenylaminopurine + TX, 2-fluoro-N-(3-methoxyphenyl)-9H-purin-6-amine + TX, benclothiaz + TX, cytokinin + TX, DCIP + TX, furfural + TX, isamidofos + TX, kinetin + TX, Myrothecium verrucaria composition + TX, tetrachlorothiophene + TX, xylenol + TX, zeatin + TX, potassium ethylxanthate + TX, benzoic acid, S-methyl ester + TX, Reynoutria sachalinensis extract + TX, α-chloroalcohol + TX,antu + TX, barium carbonate + TX, coumatetralyl + TX, bromadiolone + TX, bromethalin + TX, bromfenacoum + TX, chlorophacinone + TX, cholecalciferol + TX, chlorophacinone + TX, coumachlor + TX, coumatetralyl + TX, pyriminil + TX, difenacoum + TX, thiacoumone + TX, diphacinone + TX, calciferol + TX, flocoumafen + TX, fluoroacetamide + TX, flupyrimin + TX, flupyrimin hydrochloride + TX, ratilan + TX, phosdrin + TX, phosphorus + TX, pival + TX, pyrinuron + TX, scilliroside + TX, sodium fluoroacetate + TX, thallium sulfate + TX, warfarin + TX, 2-(2-butoxyethoxy)ethyl piperate + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone + TX, farnesol with nerolidol + TX, piperonyl butoxide + TX, MGK 264 + TX, piperonyl butoxide + TX, piperonyl aldehyde + TX, piperonyl propyl isomer + TX, S421 + TX, sesamex + TX, sesasmolin + TX, sulfoxide + TX, anthraquinone + TX, copper naphthenate + TX, copper oxychloride + TX, dicyclopentadiene + TX, silafluofen + TX, zinc naphthenate + TX, ziram + TX, emamectin benzoate + TX, ribavirin + TX, mercuric oxide + TX, thiophanate-methyl + TX, azaconazole + TX, bitertanol + TX, bofluthrin + TX, cyproconazole + TX, difenoconazole + TX, diniconazole + TX, epoxiconazole + TX, fluquinconazole + TX, flusilazole + TX, flutriafol + TX, furametpyr + TX, hexaconazole + TX, imazalil + TX, imibenconazole + TX, ipconazole + TX, metconazole + TX, myclobutanil + TX, pefurazoate + TX, penconazole + TX, prothioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyridinitril + TX, simeconazole + TX, tebuconazole + TX, fluoxastrobin + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, triticonazole + TX,Ancymidol + TX, Fenarimol + TX, Fluotrimazole + TX, Bupirimate + TX, Dimethirimol + TX, Ethirimol + TX, Dodemorph + TX, Fenpropidin + TX, Fenpropimorph + TX, Spiroxamine + TX, Tridemorph + TX, Cyprodinil + TX, Cymoxanil + TX, Pyrimethanil + TX; Anilazin + TX, Fludioxonil + TX, Benalaxyl + TX, Furalaxyl + TX, Metalaxyl + TX, R-Metalaxyl + TX; Furmecyclox + TX; Oxadixyl + TX, Carbendazim + TX, Debacarb + TX, Fuberidazole + TX, thiabendazole + TX, Chlozolinate + TX, Dichlozoline + TX, Myclozoline + TX, Procymidone + TX, Vinclozoline + TX, Boscalid + TX, Carboxin + TX, Methfuroxam + TX, Flutolanil + TX, Fenfuram + TX, oxycarboxin + TX, Penthiopyrad + TX, Thifluzamide + TX, Diethofencarb + TX, guazatine + TX, Azoxystrobin + TX, Enestroburin + TX, Kresoxim-methyl + TX, Trifloxystrobin + TX, Fluoxastrobin + TX, Triflumizole + TX, Picoxystrobin + TX, Pyraclostrobin + TX, Pyribencarb + TX, Zoxamide + TX, Ferbam + TX, Mancozeb + TX, Maneb + TX, Metiram + TX, Zineb + TX, Ziram + TX, Captafol + TX, Captan + TX, Chlorazifop + TX, Folpet + TX, Tolylfluanid + TX, Bordeaux mixture + TX, Copper oxide + TX, Copper mancozeb + TX, Copper quinolate + TX, Phthalide + TX, Kitazin + TX, IBP + TX, Chlorpyrifos-methyl + TX, Tolclofos-methyl + TX, Anilazine + TX, Benzothiazole + TX, Blasticidin + TX, Chloroneb + TX, Chlorothalonil + TX, Cyflufenamid + TX, Cymoxanil + TX, Cyflufenamid + TX, Diclocymet + TX, Diclomezine + TX, Dichloran + TX, Diethofencarb + TX, Dimethomorph + TX, Flumorph + TX, Dithianon + TX,Ethaboxam + Tx, Etridiazole + TX, Oxadixyl + Tx, Fenamidone + TX, Fenoxanil + TX, Ferimzone + TX, Fluazinam + TX, Fluopicolide + TX, Flusulfamide + TX, Fluxapyroxad + TX, Fenhexamid + TX, Fosetyl - aluminium + TX, Hymexazol + TX, Propineb + TX, Cyazofamid + TX, Methasulfocarb + TX, Metrafenone + TX, Pencycuron + TX, Phthalide + TX, Polyoxins + TX, Propamocarb + TX, Pyribencarb + TX, Proquinazid + TX, Pyroquilon + TX, Pyriofenone + TX, Quinoxyphen + TX, Quintozene + TX, Tiadinil + TX, Triazoxide + TX, Tricyclazole + TX, Triforine + TX, Validamycin + TX, Valifenalate + TX, Zoxamide + TX, Mandipropamid + TX, Flufenoxamid + TX, Isopyrazam + TX, Sedaxane + TX, Benzovindiflupyr + TX, Fluxapyroxad + TX, 3 - (Difluoromethyl) - 1 - methyl - 1H - pyrazole - 4 - carboxylic acid (3’,4’,5’ - trifluoro - biphenyl - 2 - yl) - amide + TX, Isocyclopyrazam + TX, Isotianil + TX, Dipymetitrone + TX, 6 - Ethyl - 5,7 - dioxo - pyrrolo[4,5][1,4]dithieno[1,2 - c]isothiazole - 3 - carbonitrile + TX, 2 - (Difluoromethyl) - N - [3 - ethyl - 1,1 - dimethyl - indan - 4 - yl]pyridine - 3 - carboxamide + TX, 4 - (2,6 - Difluorophenyl) - 6 - methyl - 5 - phenyl - pyridazine - 3 - carbonitrile + TX, (R) - 3 - (Difluoromethyl) - 1 - methyl - N - [1,1,3 - trimethylindan - 4 - yl]pyrazole - 4 - carboxamide + TX, 4 - (2 - Bromo - 4 - fluorophenyl) - N - (2 - chloro - 6 - fluorophenyl) - 2,5 - dimethyl - pyrazol - 3 - amine + TX, 4 - (2 - Bromo - 4 - fluorophenyl) - N - (2 - chloro - 6 - fluorophenyl) - 1,3 - dimethyl - 1H - pyrazol - 5 - amine + TX, Fluindapyrad + TX, Jiaxiangjunzhi + TX,Libenmixianan + TX, Dichlobentiazox + TX, Mandestrobin + TX, 3-(4,4-Difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone + TX, 2-[2-Fluoro-6-[(8-fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol + TX, Oxathiapiprolin + TX, N-[6-[[[(1-Methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamic acid tert-butyl ester + TX, Pyraziflumid + TX, Inpyrfluxam + TX, Trolprocarb + TX, Chlorfludioxonil + TX, Ipfentrifluconazole + TX, 2-(Difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, N'-(2,5-Dimethyl-4-phenoxyphenyl)-N-ethyl-N-methyl-formamidine + TX, N'-[4-(4,5-Dichlorothiazol-2-yl)oxy-2,5-dimethylphenyl]-N-ethyl-N-methyl-formamidine + TX, [2-[3-[2-[1-[2-[3,5-Bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chlorophenyl]methanesulfonate + TX, N-[6-[[(Z)-[(1-Methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamic acid but-3-ynyl ester + TX, N-[[5-[4-(2,4-Dimethylphenyl)-1,2,3-triazol-2-yl]-2-methylphenyl]methyl]carbamic acid methyl ester + TX, 3-Chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine + TX, Pyridachlometyl + TX, 3-(Difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 1-[2-[[1-(4-Chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methylphenyl]-4-methyl-1H-tetrazol-5-one + TX, 1-Methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]-1H-tetrazol-5-one + TX, Aminopyrifen + TX, Amisulbrom + TX, Indaziflam + TX, Fluxapyroxad + TX, (Z,2E)-5-[1-(4-Chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide + TX, Picarbutrazox + TX,Fenpicoxamid + TX, isobutyl ethoxyquinoline + TX, ipflufenoquin + TX, quinofumelin + TX, isopropylthianil + TX, N-[2-[2,4-dichlorophenoxy]phenyl]-3-(difluoromethyl)-1-methylpyrazole-4-carboxamide + TX, N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methylpyrazole-4-carboxamide + TX, benzothiazole ester + TX, cyenopyrac + TX, zinc 5-amino-1,3,4-thiadiazole-2-thiolate (2:1) + TX, fluopyram + TX, fluopyram + TX, fluoxastrobin + TX, pyrapropoyne + TX, picarbutrazox + TX, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethylinden-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylinden-4-yl)pyridine-3-carboxamide + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile + TX, metyltetraprole + TX, α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl]-5-pyrimidinemethanol + TX, fluoxapiprolin + TX, enoxastrobin + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioalkyl-1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridinyl]oxy]benzonitrile + TX, trinexapac-ethyl + TX, caryomycin + TX, zhongshengmycin + TX, thiodiazole copper + TX, thiazole zinc + TX, amectotractin + TX, iprodione + TX, N-octyl-N'-[2-(octylamino)ethyl]ethane-1,2-diamine + TX; N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxyethoxy]-3-pyridinyl]-N-ethyl-N-methylformamidine + TX,N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds can be prepared by the methods described in WO 2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX (this compound can be prepared by the methods described in IPCOM000249876D); N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine + TX, N'-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds can be prepared by the methods described in WO 2018 / 228896); N-ethyl-N'-[5-methoxy-2-methyl-4-[2-(trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine + TX, N-ethyl-N'-[5-methoxy-2-methyl-4-[2-(trifluoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine + TX (these compounds can be prepared by the methods described in WO 2019 / 110427); N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, 8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide + TX,8-Fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-((1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide + TX, N-((1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide + TX (These compounds can be prepared by the methods described in WO 2017 / 153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline + TX, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline + TX, 4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX (These compounds can be prepared by the methods described in WO 2017 / 025510); 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline + TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline + TX, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline + TX, 3-(4,4-difluoro-3,3-dimethyl-1-isoquinolinyl)-7,8-dihydro-6H-cyclopentadieno[e]benzimidazole + TX (These compounds can be prepared by the methods described in WO 2016 / 156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide + TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea + TX,1,3 - Dimethoxy - 1 - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]urea + TX, 3 - Ethyl - 1 - methoxy - 1 - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]urea + TX, N - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]propanamide + TX, 4,4 - Dimethyl - 2 - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]isoxazolidin - 3 - one + TX, 5,5 - Dimethyl - 2 - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]isoxazolidin - 3 - one + TX, Ethyl 1 - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]pyrazole - 4 - carboxylate + TX, N,N - Dimethyl - 1 - [[4 - [5 - (trifluoromethyl)-1,2,4 - oxadiazol - 3 - yl]phenyl]methyl]-1,2,4 - triazol - 3 - amine + TX. The compounds in this paragraph can be obtained from WO 2017 / 055473, WO 2017 / 055469,Prepared by the methods described in WO 2017 / 093348 and WO 2017 / 118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridinyl]-1-(1,2,4-triazol-1-yl)propan-2-ol + TX (this compound can be prepared by the method described in WO 2017 / 029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridinyl]-1-(1,2,4-triazol-1-yl)propan-2-ol + TX (this compound can be prepared by the method described in WO 2017 / 029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound can be prepared by the method described in WO 2016 / 156290); 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound can be prepared by the method described in WO 2016 / 156290); (4-phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-3-carboxylate + TX (this compound can be prepared by the method described in WO 2014 / 006945); 2,6-dimethyl-1H,5H-[1,4]dithieno[2,3-c:5,6-c']bipyrrole-1,3,5,7(2H,6H)-tetrone + TX (this compound can be prepared by the method described in WO 2011 / 138281); N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]thiobenzamide + TX; N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine + TX (this compound can be prepared by the method described in WO 2018 / 153707); N'-(2-chloro-5-methyl-4-phenoxyphenyl)-N-ethyl-N-methyl-formamidine + TX; N'-[2-chloro-4-(2-fluorophenoxy)-5-methylphenyl]-N-ethyl-N-methyl-formamidine + TX (this compound can be prepared by the method described in WO 2016 / 202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX (this compound can be prepared by the method described in WO 2014 / 095675); (5-methyl-2-pyridinyl)[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX,(3-Methylisoxazol-5-yl)[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX (These compounds can be prepared by the methods described in WO 2017 / 220485); 2-Oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX (This compound can be prepared by the methods described in WO 2018 / 065414); Ethyl 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylate + TX (This compound can be prepared by the methods described in WO 2018 / 158365); 2,2-Difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX, N-[(E)-Methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[(Z)-Methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[N-Methoxy-C-methyl-carbamimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX (These compounds can be prepared by the methods described in WO 2018 / 202428), Chloridazon + TX, Flusulfuron + TX, Fluconazole + TX, Flufenoxadiazam + TX, Metarylpicoxamid + TX.

[0527] References in brackets after the active ingredients, e.g., [3878-19-1], refer to Chemical Abstracts Registry Numbers. The mixing combinations described above are known. Where the active ingredients are included in "The Pesticide Manual", they are described therein by the entry numbers given in parentheses above for the specific compounds; for example, the compound "abamectin" is described by entry number (1). Where "[CCN]" is added above to a specific compound, the said compound is included in "Compendium of Pesticide Common Names", which is available on the Internet [A. Wood; Compendium of Pesticide Common Names, Copyright obtained in [1995 - 2004]; for example, the compound "acetoprole" is described at the Internet address http: / / www.alanwood.net / pesticides / acetoprole.html.

[0528] Most of the above active ingredients are mentioned above by means of the so - called "common name", and in a single case the corresponding "ISO common name" or another "common name" is used. If the name is not a "common name", the type of name used is replaced by the name given in parentheses for the particular compound; in this case, the IUPAC name, the IUPAC / Chemical Abstracts name, the "chemical name", the "trivial name", the "compound name", or the "development code" is used, or if neither one of those names nor the "common name" is used, the "alias" is used. "CAS Registry Number" means the Chemical Abstracts Registry Number.

[0529] A compound selected from compounds of (I), (I - A), (I - A1), (I - A2), (I - A3), (I - A4), (I - A5), (I - B), (I - C), or (I - D), or an active ingredient mixture of compounds selected from the compounds listed in Tables A - 1 to A - 26 or the compounds listed in Table P (below) is preferably in a mixing ratio of from 100:1 to 1:100, especially from 50:1 to 1:50, more especially from 20:1 to 1:20, even more especially from 10:1 to 1:10 and still more especially from 5:1 to 1:5. Those mixing ratios are by weight.

[0530] The mixtures as described above can be used in a method for controlling pests, which method comprises applying a composition comprising the mixture as described above to the pests or their environment, except for methods for treating the human or animal body by surgery or therapy and diagnostic methods practiced on the human or animal body.

[0531] Compounds comprising a compound selected from the compounds of formula (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-A5), (I-B), (I-C), or (I-D), or compounds selected from the compounds listed in Tables A-1 to A-26 or the compounds listed in Table P (below) and a mixture of one or more active ingredients as described above can be applied, for example, in a single "ready-to-use" form, in a combined spray mixture consisting of separate formulations of the individual active ingredient components, such as "tank mixing", and when applied in a sequential manner, i.e., one after the other within a reasonably short period of time (such as a few hours or days), the individual active ingredients are used in combination. The order of application of a compound selected from (I), (I-A), (I-A1), (I-A2), (I-A3), (I-A4), (I-A5), (I-B), (I-C), or (I-D), or a compound selected from the compounds listed in Tables A-1 to A-26 or the compounds listed in Table P (below) and one or more active ingredients as described above is not important for carrying out the invention.

[0532] The compositions according to the invention can also contain further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (such as epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (such as silicone oils), preservatives, viscosity regulators, binders and / or tackifiers, fertilizers or other active ingredients for obtaining specific effects, such as bactericides, fungicides, nematicides, plant activators, molluscicides or herbicides.

[0533] The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries, for example by grinding, sieving and / or compressing the solid active ingredient; and in the presence of at least one auxiliary, for example by intimately mixing the active ingredient with one or more auxiliaries and / or grinding the active ingredient together with one or more auxiliaries. These methods for preparing the compositions and the use of the compound (I) for preparing these compositions are also the subject of the invention.

[0534] Another aspect of the present invention relates to the use of a fungicidal or insecticidal mixture comprising a compound of formula (I) according to the present invention or preferably various compounds as defined herein, or a composition comprising at least one compound of formula (I) or at least one preferably various compounds as defined herein, or a composition comprising at least one compound of formula (I) or at least one preferably various compounds as defined herein (mixed with other fungicides or insecticides as described above) for controlling or preventing plants (such as useful plants, e.g., crop plants), their propagation materials (such as seeds), harvested crops (such as harvested food crops), or inanimate materials from being infested by insects or phytopathogenic microorganisms (preferably fungal organisms).

[0535] Another aspect of the present invention relates to a method for controlling or preventing plants (such as useful plants, e.g., crop plants), their propagation materials (such as seeds), harvested crops (such as harvested food crops), or inanimate materials from being infested by phytopathogenic microorganisms, spoilage microorganisms, or organisms potentially harmful to humans (especially fungal organisms), which method comprises applying a compound of formula (I) according to the present invention or preferably various compounds as defined herein as an active ingredient to these plants, parts of these plants or their sites, their propagation materials, or any part of these inanimate materials.

[0536] Controlling or preventing means reducing the infestation by insects or phytopathogenic microorganisms, spoilage microorganisms, or organisms potentially harmful to humans (especially fungal organisms) to a proven improved level.

[0537] A preferred method for controlling or preventing crop plants from being infested by phytopathogenic microorganisms (especially fungal organisms) or insects is foliar application, which method comprises applying a compound of formula (I) according to the present invention or an agrochemical composition containing at least one compound of formula (I). The application frequency and application rate will depend on the risk of infestation by the corresponding pathogen or insect. However, the compound of formula (I) according to the present invention can also penetrate plants via the roots (systemic action) through the soil by soaking the sites of the plants with a liquid formulation or by applying the compound in solid form, for example in the form of granules, to the soil (soil application). In rice crops, such granules can be applied to flooded paddy fields. The compound of formula (I) can also be applied to seeds (coating) by impregnating the seeds or tubers with a liquid formulation of the fungicide or coating them with a solid formulation.

[0538] The formulations (e.g., compositions containing a compound of formula (I) according to the invention, and (if desired) solid or liquid adjuvants or monomers for encapsulating the compound of formula (I)) can be prepared in a known manner, typically by intimately mixing and / or grinding the compound with supplements (such as solvents, solid carriers and optionally surface-active compounds (surfactants)).

[0539] Advantageous application rates are generally from 5 g to 2 kg of active ingredient (a.i.) / 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 a seed soaking reagent, appropriate dosages are from 10 mg to 1 g of active substance / kg of seed.

[0540] As used herein, the term "g a.i. / ha" refers to the application rate given in grams [g] of active ingredient [a.i.] per unit surface [ha]. The unit hectare (symbol ha) is a metric unit equal to the area of a square with a side length of 100 m (1 hm 2 ) or 10,000 square meters. The hectare is a commonly used area unit in the metric system.

[0541] When the combinations of the invention are used for treating seeds, application rates of 0.001 to 50 g of the compound of formula (I) / kg of seed, preferably from 0.01 to 10 g / kg of seed, are generally sufficient.

[0542] Suitably, the compositions comprising a compound of formula (I) according to the invention are applied prophylactically (i.e., before the development of the disease) or therapeutically (i.e., after the development of the disease).

[0543] The compositions of the invention can be used in any conventional form, e.g., in the form of a two-pack, powder for dry seed treatment (DS), emulsion for seed treatment (ES), flowable concentrate for seed treatment (FS), solution for seed treatment (LS), water dispersible powder for seed treatment (WS), capsule suspension for seed treatment (CF), gel for seed treatment (GF), emulsion concentrate (EC), suspension concentrate (SC), suspension emulsion (SE), capsule suspension (CS), water dispersible granule (WG), emulsifiable granule (EG), water-in-oil emulsion (EO), oil-in-water emulsion (EW), microemulsion (ME), dispersible oil suspension (OD), oil suspension (OF), oil-soluble liquid (OL), soluble concentrate (SL), ultra-low volume suspension (SU), ultra-low volume liquid (UL), technical concentrate (TK), dispersible concentrate (DC), wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0544] Such compositions can be produced in a conventional manner, for example by mixing the active ingredient with suitable formulation inert agents (diluents, solvents, fillers and optionally other formulation ingredients such as surfactants, biocides, antifreeze agents, adhesives, thickeners and compounds providing auxiliary effects). Conventional slow-release formulations intended for long-term sustained efficacy can also be used. In particular, formulations to be applied in spray form, such as water-dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders and granules, can contain surfactants such as wetting agents and dispersants and other compounds providing auxiliary effects, such as condensation products of formaldehyde with naphthalenesulfonates, alkylarylsulfonates, ligninsulfonates, fatty alkyl sulfates and ethoxylated alkylphenols and ethoxylated fatty alcohols.

[0545] The combination and diluent of the present invention are used to apply the seed dressing formulation to the seeds in a known manner in a suitable seed dressing formulation form, such as an aqueous suspension or dry powder form having good adhesion to the seeds. Such seed dressing formulations are known in the art. The seed dressing formulation can contain a single active ingredient or a combination of active ingredients in encapsulated form, such as in the form of slow-release capsules or microcapsules.

[0546] Generally, these formulations contain from 0.01% to 90% by weight of the active ingredient, from 0% to 20% of an agriculturally acceptable surfactant and 10% to 99.99% of a solid or liquid formulation inert agent and one or more auxiliary agents, the active ingredient being optionally composed of at least a compound of formula (I) according to the present invention together with other active ingredients (especially microbicides or preservatives, etc.). The concentrated form of the composition usually contains from about 2% to 80% by weight, preferably from about 5% to 70% by weight, of the active ingredient. The application form of the formulation can contain, for example, from 0.01% to 20% by weight, preferably from 0.01% to 5% by weight, of the active ingredient. However, commercial products will preferably be formulated as concentrates and the end user will generally use diluted formulations.

[0547] However, it is preferred to formulate commercial products as concentrates and the end user will generally use diluted formulations.

[0548] The application rates vary within a wide range and depend on the nature of the soil, the application method, the crop plant, the pest to be controlled, the main climatic conditions, and other factors governed by the application method, the application time and the target crop. Generally speaking, the compound can be applied at a rate of from 1 to 2000 l / ha, especially from 10 to 1000 l / ha.

[0549] Preferred formulations can have the following composition (% by weight):

[0550] Emulsifiable Concentrate :

[0551] Active ingredient: 1% to 95%, preferably 60% to 90%

[0552] Surfactant: 1% to 30%, preferably 5% to 20%

[0553] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0554] Powder :

[0555] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%

[0556] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%

[0557] Suspension Concentrate:

[0558] Active ingredient: 5% to 75%, preferably 10% to 50%

[0559] Water: 94% to 24%, preferably 88% to 30%

[0560] Surfactant: 1% to 40%, preferably 2% to 30%

[0561] Wettable Powder :

[0562] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0563] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0564] Solid carrier: 5% to 95%, preferably 15% to 90%

[0565] Granule:

[0566] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%

[0567] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0568] The disclosure of the present application enables each combination of the embodiments disclosed herein to be obtained.

[0569] The compounds according to Tables A-1 to A-26 below can be prepared according to the above method. The following examples are intended to illustrate the present invention and to show the preferred compounds of formula (I). In any of the following Tables A-1 to A-26, the presence of one or more possible asymmetric carbon atoms in the compounds of formula (I) according to the present invention means that these compounds can exist in chiral isomeric forms, i.e., in the form of enantiomers or diastereoisomers.

[0570] Table A : This table discloses 75 compounds of formula (Ia) according to the present invention, wherein:

[0571]

[0572] wherein G has the formula as defined below

[0573]

[0574]

[0575]

[0576]

[0577] The following compounds represent specific compounds of formula (Ia) as described in Tables A-1 to A-26, wherein G is as defined in Table A. For example, compound A-1.G1 represents a compound of formula (Ia), wherein R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and B 2 are as defined in Table A-1 and G is G1 as defined in Table A.

[0578] Table A-1: This table provides 75 compounds of formula (Ia) from A-1.G1 to A-1.G75, wherein R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is H, B 2 is CH, and G is as defined in Table A. For example, compound A-1.G3 has the following structure:

[0579] Compound A-1.G3

[0580] Table A-2: This table provides 75 compounds A-2.G1 to A-2.G75 of formula (Ia), where R 2 is CH3, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 are H, B 2 is CH, and G is as defined in Table A. For example, Compound A-2.G2 has the following structure:

[0581] Compound A-2.G2

[0582] Table A-3: This table provides 75 compounds A-3.G1 to A-3.G75 of formula (Ia), where R 2 is F, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 are H, B 2 is CH, and G is as defined in Table A.

[0583] Table A-4: This table provides 75 compounds A-4.G1 to A-4.G75 of formula (Ia), where R 2 is Cl, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 are H, B 2 is CH, and G is as defined in Table A.

[0584] Table A-5: This table provides 75 compounds A-5.G1 to A-5.G75 of formula (Ia), where R 2 is cyclopropyl, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 are H, B 2is CH, and G is as defined in Table A.

[0585] Table A-6: This table provides 75 compounds of formula (Ia), A-6.G1 to A-6.G75, where R 2 is COCH3, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is H, B 2 is CH, and G is as defined in Table A.

[0586] Table A-7: This table provides 75 compounds of formula (Ia), A-7.G1 to A-7.G75, where R 2 is C=N(OCH3)CH3, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is H, B 2 is CH, and G is as defined in Table A.

[0587] Table A-8: This table provides 75 compounds of formula (Ia), A-8.G1 to A-8.G75, where R 2 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is H, R 4 is CH3, B 2 is CH, and G is as defined in Table A. For example, compound A-8.G32 has the following structure:

[0588] Compound A-8.G32

[0589] Table A-9: This table provides 75 compounds of formula (Ia), A-9.G1 to A-9.G75, where R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is H, R 2 and R 4 is CH3, B2 is CH, and G is as defined in Table A.

[0590] Table A-10: This table provides 75 compounds A-10.G1 to A-10.G75 having formula (Ia), where R 5 , R 6 , R 7 , R 8 , R 9 , R 10 is H, R 2 and R 4 are CH3, B 2 is N, and G is as defined in Table A.

[0591] Table A-11: This table provides 75 racemic-compounds A-11.G1 to A-11.G75 having formula (Ia), where R 5 , R 6 , R 8 , R 9 , R 10 is H, R 2 and R 7 are CH3, B 2 is CH, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other. For example, the compound racemic-A-11.G2 has the following structure

[0592] Compound racemic-A-11.G2

[0593] Table A-12: This table provides 75 racemic-compounds A-12.G1 to A-12.G75 having formula (Ia), where R 5 , R 6 , R 8 , R 9 , R 10 is H, R 2 is Cl, R 7 is CH3, B 2 is CH and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other. For example, the compound racemic-A-12.G67 has the following structure;

[0594] Compound racemic-A-12.67

[0595] Table A-13:This table provides 75 compounds A-13.G1 to A-13.G75 having formula (Ia), wherein R 5 、R 6 、R 8 、R 9 、R 10 is H, R 2 、R 7 and R 4 is CH3, B 2 is CH, and G is as defined in Table A.

[0596] Table A-14: This table provides 75 racemic-compounds A-14.G1 to A-14.G75 having formula (Ia), wherein R 5 、R 6 、R 8 、R 9 、R 10 is H, R 2 and R 7 is CH3, B 2 is C-Br, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other.

[0597] Table A-15: This table provides 75 racemic-compounds A-15.G1 to A-15.G75 having formula (Ia), wherein R 5 、R 6 、R 8 、R 9 、R 10 is H, R 2 and R 7 is CH3, B 2 is C-CN, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other.

[0598] Table A-16: This table provides 75 racemic-compounds A-16.G1 to A-16.G75 having formula (Ia), wherein R 5 、R 6 、R 8 、R 9 、R 10 is H, R 2 is Cl, R 7 is CH3, B 2 is C-Cl, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other.

[0599] Table A-17: This table provides 75 racemic-compounds A-17.G1 to A-17.G75 having the formula (Ia), wherein R 5 , R 6 , R 8 , R 9 , R 10 is H, R 2 is Cl, R 7 is CH3, B 2 is C-CN, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other. For example, the compound racemic-A-17.G53 has the following structure;

[0600] Compound racemic-A-17.G53

[0601] Table A-18: This table provides 15 compounds A-18.G1 to A-18.G15 having the formula (Ia), wherein R 4 , R 5 , R 6 , R 8 , R 9 and R 10 are H, R 2 and R 7 are CH3, B 2 is N and G is as defined in Table A.

[0602] Table A-19: This table provides 15 racemic-compounds A-19.G1 to A-19.G15 having the formula (Ia), wherein R 4 , R 5 , R 6 , R 8 and R 10 are H, R 9 is OCH3, R 2 and R 7 are CH3, B 2 is C-Cl, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis-relationship to each other. For example, the compound racemic-A-19.G15 has the following structure

[0603] Compound racemic-A-19.G15

[0604] Table A-20:This table provides 15 racemic - compounds A - 20.G1 to A - 20.G15 having the formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 10 are H, R 9 is OCH3, R 2 and R 7 are CH3, B 2 is C - H, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis - relationship with each other.

[0605] Table A-21: This table provides 15 racemic - compounds A - 21.G1 to A - 21.G15 having the formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 10 are H, R 9 is Br, R 2 and R 7 are CH3, B 2 is C - H, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis - relationship with each other.

[0606] Table A-22: This table provides 15 racemic - compounds A - 22.G1 to A - 22.G15 having the formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 10 are H, R 9 is Cl, R 2 and R 7 are CH3, B 2 is C - H, and G is as defined in Table A. In this table, the pyrazole substituent and the R 7 CH3 substituent have a cis - relationship with each other.

[0607] Table A-23: This table provides 15 racemic - compounds A - 23.G1 to A - 23.G15 having the formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 10 are H, R 9 is CN, R2 and R 7 is CH3, B 2 is C-H, and G is as defined in Table A. In this table, the pyrazole substituent and R 7 CH3 substituents have a cis-relationship to each other.

[0608] Table A-24: This table provides 15 racemic-compounds A-24.G1 to A-24.G15 of formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 9 is H, R 10 is Br, R 2 and R 7 is CH3, B 2 is C-H, and G is as defined in Table A. In this table, the pyrazole substituent and R 7 CH3 substituents have a cis-relationship to each other.

[0609] Table A-25: This table provides 15 racemic-compounds A-25.G1 to A-25.G15 of formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 9 is H, R 10 is Cl, R 2 and R 7 is CH3, B 2 is C-H, and G is as defined in Table A. In this table, the pyrazole substituent and R 7 CH3 substituents have a cis-relationship to each other.

[0610] Table A-26: This table provides 15 racemic-compounds A-26.G1 to A-26.G15 of formula (Ia), wherein R 4 、R 5 、R 6 、R 8 and R 9 is H, R 10 is CN, R 2 and R 7 is CH3, B 2 is C-H, and G is as defined in Table A. In this table, the pyrazole substituent and R 7 CH3 substituents have a cis-relationship to each other. For example, compound A-26.G6 has the following structure:

[0611] Compound racemic - A - 26.G6

[0612] Examples

[0613] The following examples are used to illustrate the invention and are not meant to limit the invention in any way.

[0614] The compounds of the invention may differ from known compounds in greater efficacy at low application rates, which can be confirmed by a person of ordinary skill in the art using the experimental procedures outlined in the examples, using lower application rates (if necessary), for example, 60 ppm, 20 ppm or 2 ppm.

[0615] Compounds having the formula (I) can have many advantages, including in particular a favorable level of biological activity for protecting plants against diseases caused by fungi or superior properties for use as active ingredients in agrochemicals (e.g., higher biological activity, favorable activity profile, increased safety (including improved crop tolerance), improved physico - chemical properties, or increased biodegradability).

[0616] Throughout this specification, temperatures are given in degrees Celsius and “m.p.” means melting point. LC / MS means liquid chromatography - mass spectrometry, and the description of the apparatus and methods is as follows.

[0617] Recorded on a Bruker 400 MHz spectrometer 1 1H NMR and 19 19F NMR measurements, chemical shifts relative to TMS ( 1 1H) and CFCl3 ( 19 19F) standards are given in ppm. The spectra are measured in the deuterated solvents as specified. The compounds are characterized by any of the following LCMS methods. The characteristic LCMS values obtained for each compound are the retention time (“Rt”, recorded in minutes) and the measured molecular ion (M + H) + or (M - H) - .

[0618] LC-MS Method A:The spectra were recorded on a mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) from Waters, which was equipped with an electrospray source (polarity: positive and negative ions, capillary: 3.00 kV, cone voltage range: 30 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 350 °C, cone gas flow rate: 50 l / h, desolvation gas flow rate: 650 l / h, mass range: 100 to 900 Da) and an Acquity UPLC from Waters: binary pump, heated column compartment, diode array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 x 2.1 mm, temperature: 60 °C, DAD wavelength range (nm): 210 to 500, solvent gradient: A = water + 5% MeOH + 0.05% HCOOH, B = acetonitrile + 0.05% HCOOH; gradient: 10% - 100% B, within 1.2 min; flow rate (ml / min): 0.85.

[0619] LC-MS Method B: The spectra were recorded on an ACQUITY mass spectrometer (SQD or SQDII single quadrupole mass spectrometer) from Waters, which was equipped with an electrospray source (polarity: positive or negative ions), capillary: 3.0 kV, cone: 30 V, extractor: 3.00 V, source temperature: 150 °C, desolvation temperature: 400 °C, cone gas flow rate: 60 L / hr, desolvation gas flow rate: 700 L / hr, mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters, which had a solvent degassing device, binary pump, heated column compartment and diode array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 x 2.1 mm, temperature: 60 °C, DAD wavelength range (nm): 210 to 400, solvent gradient: A = water / methanol 9:1 + 0.1% formic acid, B = acetonitrile + 0.1% formic acid, gradient: 0% - 100% B, within 2.5 min; flow rate (ml / min) 0.75.

[0620] LC-MS Method C:Spectra were recorded on a mass spectrometer (Acquity QDa mass spectrometer) from Waters, equipped with an electrospray source (polarity: positive and negative polarity switching, capillary: 0.8 kV, cone voltage range: 25 V, extractor: V (no extractor voltage for Qda detector), source temperature: 120 °C, desolvation temperature: 600 °C, cone gas flow: 50 L / h, desolvation gas flow: 1000 L / h, mass range: 110 to 850 Da) and an Acquity UPLC from Waters: quaternary solvent manager, heated column compartment, diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30 x 2.1 mm, temperature: 40 °C, DAD wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: gradient: 0 min 10% B; 0. - 0.2 min 10% - 50% B; 0.2 - 0.6 min 50% - 100% B; 0.6 - 1.3 min 100% B; 1.3 - 1.4 min 100% - 10% B; 1.4 - 1.6 min 10% B; flow rate (mL / min) 0.6.

[0621] LC-MS Method D: Spectra were recorded on a mass spectrometer (SQD2 or QDA single quadrupole mass spectrometer) from Waters, equipped with an electrospray source (polarity: positive and negative polarity switching), capillary: 0.8 - 3.00 kV, cone voltage range: 25, source temperature: 120 °C - 150 °C, desolvation temperature: 500 °C - 600 °C, cone gas flow: 50 L / h, desolvation gas flow: 1000 L / h, mass range: 110 to 850 Da) and an Acquity UPLC from Waters: quaternary solvent manager, heated column compartment, diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30 x 2.1 mm, temperature: 40 °C, DAD wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: gradient: 0 min 10% B; 0. - 0.2 min 10% - 50% B; 0.2 - 0.6 min 50% - 100% B; 0.6 - 1.3 min 100% B; 1.3 - 1.4 min 100% - 10% B; 1.4 - 1.6 min 10% B; flow rate (mL / min) 0.6.

[0622] LC-MS Method E:Spectra were recorded on a mass spectrometer (6410 triple quadrupole mass spectrometer) from Agilent Technologies, equipped with an electrospray source (polarity: positive or negative ions, MS2 scan, capillary voltage: 4.00 kV, fragmentation voltage: 100 V, desolvation temperature: 350 °C, gas flow: 11 L / min, nebulizer gas: 45 psi, mass range: 110 to 1000 Da) and a 1200 series HPLC from Agilent: quaternary pump, heated column compartment and VWD detector. Column: KINETEX EVO C18, 2.6 μm, 50 x 4.6 mm, temperature: 40 °C, detector VWD wavelength: 254 nm, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.1% HCOOH; gradient: 0 min 10% B, 90% A; 0.9 - 1.8 min 100% B; 1.8 - 2.2 min 100% - 10% B; 2.2 - 2.5 min 10% B; flow rate (mL / min) 1.8.

[0623] Formulation Example

[0624]

[0625] The combination was thoroughly mixed with these adjuvants and the mixture was thoroughly ground in a suitable grinder to obtain a wettable powder that could be diluted with water to give a suspension of the desired concentration.

[0626]

[0627] The combination was thoroughly mixed with the adjuvants and the mixture was thoroughly ground in a suitable grinder to obtain a powder that could be directly used for seed treatment.

[0628] Emulsifiable Concentrate

[0629]

[0630] Emulsions of any required dilution that can be used in plant protection can be obtained by diluting this concentrate with water.

[0631]

[0632] Ready-to-use dusts are obtained by mixing the combination with a carrier and grinding the mixture in a suitable grinder. Such dusts can also be used for dry dressing of seeds.

[0633] Extruded Granule

[0634]

[0635]

[0636] Mix the combination with these auxiliaries and grind, and moisten the mixture with water. Extrude the mixture and then dry it in an air stream.

[0637] Coated Granule

[0638] Active ingredient 8%

[0639] Polyethylene glycol (molecular weight 200) 3%

[0640] Kaolin 89%

[0641] Apply the finely ground combination uniformly to kaolin moistened with polyethylene glycol in a mixer. In this way, dust-free coated granules are obtained.

[0642] Suspension Concentrate

[0643]

[0644] Mix the finely ground combination tightly with the auxiliaries to obtain a suspension concentrate. From this suspension concentrate, suspensions of any desired dilution can be obtained by diluting with water. Using such dilutions, living plants together with plant propagation materials can be treated and protected against microbial infestation by spraying, watering or dipping.

[0645] Flowable Concentrate for Seed Treatment

[0646]

[0647]

[0648] Mix the finely ground combination thoroughly with the auxiliaries to obtain a suspending agent. From this suspending agent, solutions of any desired dilution can be obtained by diluting with water, which can be directly used for seed treatment. Using such dilutions, living plants together with plant propagation materials can be treated and protected against microbial infestation by spraying, watering or dipping.

[0649] Sustained Release Capsule Suspension

[0650] A combination of 28 parts is mixed with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 part of an antifoaming agent, and 51.6 parts of water until the desired particle size is achieved. 2.8 parts of a 1,6-hexanediamine mixture in 5.3 parts of water are added to this emulsion. The mixture is stirred until the polymerization reaction is complete. The obtained capsule suspension is stabilized by adding 0.25 part of a thickening agent and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredient. The diameter of the medium capsules is 8 - 15 microns. The resulting formulation is applied to the seeds as an aqueous suspension in a device suitable for this purpose.

[0651] Formulation types include emulsion concentrate (EC), suspension concentrate (SC), suspoemulsion (SE), capsule suspension (CS), water dispersible granule (WG), emulsifiable granule (EG), emulsion, water-in-oil emulsion (EO), oil-in-water emulsion (EW), microemulsion (ME), oil dispersion (OD), oil suspension (OF), oil soluble liquid (OL), soluble concentrate (SL), ultra-low volume suspension (SU), ultra-low volume liquid (UL), technical material (TK), dispersible concentrate (DC), wettable powder (WP), soluble granule (SG), or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0652] Abbreviation

[0653] CDCl3 deuterated chloroform

[0654] DABCO 1,4-diazabicyclo[2.2.2]octane, also known as triethylenediamine or TEDA

[0655] DCC dicyclohexylcarbodiimide

[0656] DMF dimethylformamide

[0657] DMSO dimethyl sulfoxide

[0658] DMSO-d6 deuterated dimethyl sulfoxide

[0659] EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

[0660] Et3N triethylamine

[0661] EtOAc ethyl acetate

[0662] HATU 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate

[0663] HCl Hydrochloric acid

[0664] h / hrs Hour(s)

[0665] LC-MS Liquid chromatography-mass spectrometry (LC-MS or LCMS)

[0666] rh Relative humidity

[0667] rt Room temperature

[0668] Rt Retention time

[0669] ssp. Subspecies

[0670] T3P Propane phosphonic anhydride, also known as 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide

[0671] THF Tetrahydrofuran

[0672] Preparation Example

[0673] The compounds of formula (I) according to the present invention can be prepared using the synthetic techniques described above and below.

[0674] “Mp” refers to the melting point in °C. The radical represents a methyl group. Recorded on a Bruker 400 MHz spectrometer (or 600 MHz as indicated) 1 1H NMR and 19 19F NMR measurements, chemical shifts relative to TMS( 1 1H) and CFCl3( 19 19F) standards given in ppm. Spectra measured in deuterated solvents as specified. Characterize these compounds using any of the following LC-MS methods. The characteristic LCMS values obtained for each compound are the retention time (“Rt”, recorded in minutes) and the measured molecular ion (M+H) + or (M-H) - .

[0675] Example P1: [5-(3,5-Difluoro-2-pyridinyl)isoxazol-3-yl]-[racemic-(1S,4S)-4-(1,5-dimethyl pyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-6, Table P) Synthesis

[0676] (Compound P-6, Table P)

[0677] Step 1: Preparation of 3,5-Difluoro-N-methoxy-N-methyl-pyridine-2-carboxamide

[0678]

[0679] Under an argon atmosphere, a suspension of 3,5-difluoropyridine-2-carboxylic acid (CAS: [745784-04-7], 2.0 g, 11.94 mmol) and N,O-dimethylhydroxylamine hydrochloride (1.248 g, 12.54 mmol) in EtOAc (47 mL) was treated with 50% by mass of 1-propane phosphonic anhydride in EtOAc (14.22 mL, 23.89 mmol), followed by treatment with N,N-diisopropylethylamine (6.26 mL, 35.83 mmol). The resulting reaction mixture was stirred under argon at room temperature for 18 hours and then diluted with aqueous Na2CO3, water, and EtOAc. The aqueous phase was extracted with EtOAc, and the combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give the title compound, which was used without further purification.

[0680] LC-MS (Method A): 203 [M+H], Rt: 0.56 min

[0681] 1 H NMR (400 MHz, CDCl3) δ ppm: 3.41 (br s, 3H) 3.62 (br s, 3H) 7.30 - 7.33 (dd, 1H) 8.39 (d, J = 2.18 Hz, 1H)

[0682] Step 2: Preparation of 1-(3,5-Difluoro-2-pyridinyl)ethenone

[0683]

[0684] Under argon, a solution of methylmagnesium bromide (7.9 mL, 23.59 mmol) was added dropwise to a cooled light brown solution (0 °C - 5 °C) of 3,5-difluoro-N-methoxy-N-methyl-pyridine-2-carboxamide (2.38 g, 11.79 mmol) in THF (35 mL). The resulting suspension was allowed to reach room temperature and stirred under an argon atmosphere for 30 minutes. The reaction mixture was slowly quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give the title compound.

[0685] LC-MS (Method A): 158 [M+H], Rt: 0.62 min

[0686] 1 H NMR (400 MHz, CDCl3) δ ppm: 2.71 (d, J = 1.09 Hz, 3H) 7.29 - 7.36 (m, 1H) 8.40 - 8.44 (d, 1H)

[0687] Step 3: Preparation of Ethyl 4-(3,5-Difluoro-2-pyridinyl)-2,4-dioxo-butyrate

[0688]

[0689] At room temperature, a solution of 1-(3,5-difluoro-2-pyridyl)ethanone (1.79 g, 11.4 mmol) in toluene (11.4 mL) was treated with diethyl oxalate (1.72 mL, 12.5 mmol), followed by treatment with potassium tert-butoxide (1.58 g, 13.7 mmol). The resulting suspension was stirred at room temperature for 17 h. The reaction mixture was then slowly quenched with 2 N aqueous HCl and extracted twice with EtOAc. The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the crude product, which was purified by flash chromatography eluting with EtOAc / cyclohexane to give the title compound.

[0690] LC-MS (method A): 258 [M+H], Rt: 0.88 min

[0691] 1 1H NMR (400 MHz, CDCl3) δ ppm: 1.38 - 1.48 (t, 3H) 4.43 (q, J = 7.27 Hz, 2H) 7.38 (ddd, J = 10.35, 7.99, 2.36 Hz, 1H) 7.51 (s, 1H) 8.49 (d, J = 2.18 Hz, 1H) 14.23 - 14.68 (br s, 1H)

[0692] Step 4: Preparation of Ethyl 5-(3,5-Difluoro-2-pyridinyl)isoxazole-3-carboxylate

[0693]

[0694] A sample of hydroxylamine hydrochloride (0.153 g, 2.18 mmol) was added to a stirred pale brown suspension of ethyl 4-(3,5-difluoro-2-pyridyl)-2,4-dioxobutyrate (0.374 g, 1.45 mmol) in ethanol (5 mL), and the resulting suspension was stirred at 50 °C for 22 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between saturated aqueous Na2CO3 and EtOAc. The aqueous phase was extracted with EtOAc, and the combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash silica chromatography eluting with EtOAc / cyclohexane to give the title compound.

[0695] LC-MS (method A): 255 [M+H], Rt: 0.89 min

[0696] 11H NMR (400 MHz, CDCl3) δ ppm: 1.45 - 1.51 (t, 3H) 4.48 - 4.55 (q, 2H) 7.27 - 7.29 (d, 1H) 7.43 (ddd, J=10.08, 7.72, 2.18 Hz, 1H) 8.55 (d, J=2.54 Hz, 1H)

[0697] Step 5: Preparation of 5-(3,5-Difluoro-2-pyridinyl)isoxazole-3-carboxylic Acid

[0698]

[0699] A solution of ethyl 5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxylate (0.111 g, 0.437 mmol) in THF (2 mL) and H2O (0.5 mL) was treated with lithium hydroxide monohydrate (0.027 g, 0.65 mmol) (added subsequently), and the reaction mixture was stirred at room temperature for 19 h. Thereafter, the mixture was acidified with 1 N aqueous HCl and extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford the title compound as a white solid.

[0700] LC-MS (Method A): 227 [M+H], Rt: 0.52 min

[0701] Step 6: Preparation of (1,5-Dimethylpyrazol-4-yl)-phenyl-methanol

[0702]

[0703] A sample of 1-methyl-1H-pyrazole-4-carbaldehyde (25 g, 201.39 mmol) dissolved in THF (400 mL) was treated with 1 molar phenylmagnesium bromide in THF (228 mL, 227.57 mmol) (added dropwise at 0 °C - 5 °C under an argon atmosphere over 15 min). After addition, the ice bath was removed and the white suspension was stirred at room temperature for 3 h. The reaction mixture was poured into saturated ammonium chloride solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to afford the crude product as a colorless oil. The crude material was purified by gradient elution on SiO2 with EtOAc:EtOH 3:1 / cyclohexane to afford the desired product (1-methylpyrazol-4-yl)-phenyl-methanol as a colorless oil.

[0704] LCMS (Method A): m / z (M+H) 203, retention time 0.68 min

[0705] 11H NMR (400 MHz, CDCl3) δ ppm: 2.23 (s, 3H) 2.28 (d, J = 4.00 Hz, 1H) 3.76 (s, 3H) 5.80 (d, J = 3.63 Hz, 1H) 7.22 (s, 1H) 7.27 - 7.32 (m, 1H) 7.33 - 7.44 (m, 4H)

[0706] Step 7: Preparation of 2-(1,5-Dimethylpyrazol-4-yl)-2-phenyl-acetonitrile

[0707]

[0708] (1-Methylpyrazol-4-yl)-phenyl-methanol (4.5 g, 22 mmol) and DCM (45 mL) were charged into a round-bottom flask equipped with a magnetic stir bar and a condenser. Then, lithium carbonate (0.33 g, 4.4 mmol), trimethylsilyl cyanide (10 g, 13 mL, 100 mmol) and iodine (10 g, 40 mmol) were added successively at room temperature. The reaction mixture was stirred at 35 °C for 1 h. Then the reaction mixture was cooled to room temperature and poured into saturated sodium thiosulfate (250 mL), and extracted with DCM (2 × 100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product, which was purified by combiflash (silica gel, gradient: EtOAC in cyclohexane) to give the desired title compound as a yellow oil.

[0709] LCMS (Method A): m / z (M+H) 212, retention time 0.82 min

[0710] 1 1H NMR (400 MHz, CDCl3-d) δ ppm: 7.46 - 7.28 (m, 6H), 5.05 (s, 1H), 3.78 (s, 3H), 2.18 (s, 3H)

[0711] Step 8: Preparation of 2-(1,5-Dimethylpyrazol-4-yl)-2-phenyl-ethylamine (Option A)

[0712]

[0713] Charge a 750 mL three-necked flask equipped with a magnetic stir bar with 2-(1-methylpyrazol-4-yl)-2-phenyl-propanenitrile (11 g, 52.06 mmol) and THF (160 mL). Under argon atmosphere at room temperature, add borane dimethyl sulfide complex (12.62 g, 15.8 mL, 156.2 mmol) dropwise to the yellow solution, and stir the resulting colorless reaction mixture at 65 °C for 2 h. Cool the reaction mixture to 0 °C, then add hydrochloric acid (23 g, 34.71 mL, 208.2 mmol) dropwise (strong gas evolution), and stir the reaction mixture at 65 °C for 1 h and let it stand overnight at room temperature. Dilute the mixture with water and treat with 6 M NaOH (to pH 12). Extract the mixture twice with EtOAc and wash the combined organic layers with brine, dry over Na2SO4 and concentrate in vacuo to give the title compound as a yellow oil, which is used in the next step without further purification.

[0714] LCMS (Method A): m / z (M+H) 216, retention time 0.60 min

[0715] 1 H NMR (400 MHz, CDCl3) δ ppm: 2.09 (s, 3H) 3.20 (dd, J = 7.45, 2.00 Hz, 2H) 3.75 (s, 3H) 3.79 (t, J = 7.27 Hz, 1H) 7.16 - 7.25 (m, 3H) 7.26 - 7.33 (m, 2H) 7.42 (s, 1H)

[0716] Preparation of 2-(1,5-Dimethylpyrazol-4-yl)-2-phenyl-ethylamine (Option B)

[0717] Option B - Step A: Preparation of 1,5-Dimethyl-4-(2-nitro-1-phenyl-ethyl)pyrazole

[0718]

[0719] A solution of 4-iodo-1,5-dimethyl-pyrazole (2.6 g, 12 mmol) in THF (40 mL) was degassed with argon and treated with isopropylmagnesium chloride-lithium complex (Turbo-Grignard, 1.3 mol / L in THF, 12 mL, 16 mmol) at 0 °C - 5 °C and under argon. The resulting white suspension was stirred at 0 °C - 5 °C for 20 min and then treated at 0 °C - 5 °C with a solution of [(E)-2-nitrovinyl]benzene (1.5 g, 9.9 mmol) in THF (5 mL). The mixture was stirred at 0 °C - 5 °C for 40 min and then at room temperature for 1 h, at which point LCMS analysis showed completion of the reaction. The reaction mixture was quenched with ice water and acidified to pH 5 by addition of 2 M aqueous HCl. The aqueous phase was extracted 3× with EtOAc, then the combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography eluting with a gradient of cyclohexane + 0 - 40 EA / EtOH 3:1 to give the title compound

[0720] LC-MS (method A): 246 [M+H], Rt: 0.84 min

[0721] 1 H NMR (400 MHz, CDCl3) δ ppm: 7.40 - 7.44 (m, 1H) 7.30 - 7.36 (m, 2H) 7.23 - 7.29 (m, 3H) 4.88 (d, J = 1.1 Hz, 1H) 4.86 (s, 1H) 4.74 (d, J = 7.6 Hz, 1H) 3.77 (s, 3H) 2.15 (s, 3H)

[0722] The two enantiomers of the title compound were separated by chiral column using the following method:

[0723] Sepiatec Prep SFC M5, column: Daicel IB, 5 □m, 2.0 cm × 25 cm, mobile phase: A: CO2, B: IPA, no gradient: 4% B, back pressure: 150 bar, GLS: -, flow rate: 90 ml / min, detection: UV 220 nm, sample concentration: 1.6 g in 25 ml ACN / MeOH (1 / 1), injection: 500 μl

[0724] Option B - Step B: Preparation of 2-(1,5-Dimethylpyrazol-4-yl)-2-phenyl-ethylamine

[0725]

[0726] A solution of 1,5-dimethyl-4-(2-nitro-1-phenylethyl)pyrazole (35 mg, 0.1427 mmol) in absolute ethanol (3 mL) was treated with platinum 1% vanadium 2% supported on activated carbon (Evonik P8078, 0.00014 mmol, 0.0070 g). The mixture was degassed and hydrogenated at 50 °C and 10 bar H2 for 18 h. The reaction mixture was filtered through a pad of diatomaceous earth and evaporated to afford the title compound. Spectral data are as in Example 1 step 8, see above.

[0727] Step 9: Preparation of Methyl N-[2-(1,5-Dimethylpyrazol-4-yl)-2-phenyl-ethyl]carbamate

[0728] A three-necked flask equipped with a mechanical stirrer was charged with 2-(1,5-dimethylpyrazol-4-yl)-2-phenylethylamine (3.5 g, 16 mmol, sample from Option A step 8), ethyl acetate (65 mL) and TEA (6.8 mL, 49 mmol). Methyl chloroformate (1.5 mL, 20 mmol) was then added dropwise over 30 min at 0 °C under an argon atmosphere, and the mixture was stirred at room temperature for 1 h. The reaction mixture was poured into water (800 mL) and extracted with EtOAc (2 × 150 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography (80 g SiO2, eluting with an EtOAc / cyclohexane gradient) to afford methyl N-[2-(1,5-dimethylpyrazol-4-yl)-2-phenylethyl]carbamate.

[0729] LC-MS (Method A): retention time 0.76 min, 274 (M+H)

[0730] 1 1H NMR (400 MHz, CDCl3) δ ppm: 2.03 - 2.13 (m, 3H) 3.62 - 3.74 (m, 5H) 3.77 (s, 3H) 3.94 - 4.05 (m, 1H) 4.72 (br s, 1H) 7.21 - 7.26 (m, 3H) 7.27 - 7.34 (m, 2H) 7.38 (s, 1H)

[0731] Step 10: Preparation of Methyl (1S,4S)-4-(1,5-Dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-iso quinoline-2-carboxylate

[0732]

[0733] Charge a single-necked round-bottom flask equipped with a magnetic stir bar with methyl N-[2-(1,5-dimethylpyrazol-4-yl)-2-phenylethyl]carbamate (2.0 g, 7.3 mmol), hydrochloric acid (concentrated, 37 mL, 450 mmol), and acetaldehyde (0.83 mL, 15 mmol). Stir the reaction mixture at room temperature for 2 h. Slowly pour the reaction mixture into water (500 mL) and slowly neutralize it in portions with NaHCO3 (strong gas evolution) to pH 8. Extract the mixture with EtOAc (3 × 50 mL), and wash the combined organic layers with brine, dry over sodium sulfate, and concentrate in vacuo. Purify the crude product by chromatography to obtain methyl (1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinoline-2-carboxylate as a single cis-diastereoisomer, characterized by 1 1H NMR analysis.

[0734] LC-MS (method A): retention time 0.87 min, 300 (M+H)

[0735] 1 1H NMR (400 MHz, CDCl3) δ ppm: 1.56 (d, J = 6.90 Hz, 3H); 2.18 (br s, 3H); 3.02 - 3.27 (m, 1H); 3.76 (br s, 3H); 3.83 (s, 3H); 3.97 - 4.09 (m, 1H); 4.09 - 4.37 (m, 1H); 5.18 - 5.45 (m, 1H); 6.86 - 7.02 (m, 1H); 7.04 - 7.24 (m, 4H).

[0736] Step 11: Preparation of (1S,4S)-4-(1,5-Dimethylpyrazol-4-yl)-1-methyl-1,2,3,4-tetrahydroiso quinoline

[0737]

[0738] Charge a 100 mL single-necked round-bottom flask equipped with a magnetic stir bar with methyl (1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinoline-2-carboxylate (1.3 g, 4.1 mmol), 1,2-dichloroethane (21 mL), and trimethylsilyl iodide (1.7 mL, 12 mmol). Under an argon atmosphere, stir the reaction mixture at 60 °C for 1 h. Cool the reaction to room temperature, then add 10% aqueous HCl (22 mL) to the reaction with ice-cooling. Remove the organic solvent in vacuo and adjust the aqueous residue to pH 8 with 10% aqueous NaOH, and then extract with DCM. Wash the combined organic layers over M gIt was dried over SO4, filtered and concentrated in vacuo to give racemic-(1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline, which was pure enough to be used without further purification.

[0739] LC-MS (Method A): retention time 0.35 min, 242 (M+H)

[0740] 1 1H NMR (600 MHz, CDCl3) δ ppm: 1.86 (d, J = 6.9 Hz, 3H) 2.23 (s, 3H) 3.27 (dd, J = 12.5, 10.8 Hz, 1H) 3.59 (dd, J = 12.8, 5.6 Hz, 1H) 3.83 (s, 3H) 4.58 (dd, J = 10.6, 5.4 Hz, 1H) 4.80 (q, J = 6.8 Hz, 1H) 7.00 (d, J = 7.8 Hz, 1H) 7.11 (s, 1H) 7.16 (d, J = 7.6 Hz, 1H) 7.18 - 7.22 (m, 1H) 7.25 - 7.28 (m, 1H)

[0741] Step 12: [5-(3,5-Difluoro-2-pyridinyl)isoxazol-3-yl]-[racemic-(1S,4S)-4-(1,5-dimethyl Synthesis of [5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-6, Table P)

[0742] Under argon, a solution of 5-(3,5-difluoro-2-pyridyl)isoxazole-3-carboxylic acid (0.040 g, 0.18 mmol) and racemic-(1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline (0.043 g, 0.18 mmol) in EtOAc (1 mL) was treated with 50% by mass 1-propane phosphonic anhydride in EtOAc (0.21 mL, 0.36 mmol), followed by treatment with N,N-diisopropylethylamine (0.093 mL, 0.53 mmol). The reaction mixture was stirred at room temperature under argon for 1 h, diluted with EtOAc and quenched with aqueous NaHCO3. The organic phase was separated and the aqueous phase was back-extracted with EtOAc. The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography eluting with EtOAc / cyclohexane to give the title compound.

[0743] LC-MS (Method A): 450 [M+H], Rt: 0.98 min

[0744] 11H NMR (400 MHz, CDCl3) δ ppm: 1.65 - 1.78 (d, 3H) 2.20 - 2.37 (s, 3H) 3.20 - 3.55 (m, 1H) 3.80 - 3.89 (d, 3H) 4.15 - 4.89 (m, 2H) 5.62 - 5.94 (m, 1H) 7.00 - 7.09 (m, 1H) 7.09 - 7.30 (m, 5H) 7.35 - 7.49 (m, 1H) 8.55 (d, J = 2.18 Hz, 1H)

[0745] Example P2: Preparation of [5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol- 4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-7, Table P)

[0746] (Compound P - 7, Table P)

[0747] Step 1: Preparation of 3,5-difluoropyridine-2-carbonyl chloride

[0748]

[0749] Under an argon atmosphere, a solution of 3,5 - difluoropyridine - 2 - carboxylic acid (CAS: [745784 - 04 - 7], 1 g, 6.28 mmol) in EtOAc (20 mL) was treated with oxalyl chloride (0.830 mL, 9.42 mmol) and then with a catalytic amount (3 - 4 drops) of DMF. The reaction mixture was stirred at room temperature for 1 hour and then concentrated in vacuo and used immediately for the next step.

[0750] Step 2: Preparation of tert-butyl N-[(3,5-difluoropyridine-2-carbonyl)amino]carbamate

[0751]

[0752] At room temperature and under an argon atmosphere, a solution of tert - butyl N - amino carbamate (0.827 g, 6.26 mmol) and N,N - diethylethylamine (1.75 mL, 12.5 mmol) in EtOAc (12 mL) was added dropwise to a solution of 3,5 - difluoropyridine - 2 - carbonyl chloride (1.17 g, 6.26 mmol) in EtOAc (12 mL). The reaction mixture was stirred at room temperature for 1 hour and then quenched with water, extracted with EtOAc (2×40 ml), and the combined organic phases were dried over Na2SO4 and concentrated in vacuo to give the pure title compound, which was used without further purification.

[0753] LC - MS (Method C): 174 [M + H - Boc], Rt: 0.57 min

[0754] 11H NMR (CDCl3) δ ppm: 1.26 (s, 1H), 1.32 (s, 1H), 1.46 - 1.48 (m, 1H), 1.51 (s, 9H), 6.56 - 6.76 (m, 1H), 7.27 (s, 1H), 7.36 (ddd, J = 10.10, 7.97, 2.31 Hz, 1H), 8.32 (d, J = 2.25 Hz, 1H), 9.13 (br s, 1H)

[0755] Step 3: Preparation of 3,5-difluoropyridine-2-carbohydrazide

[0756]

[0757] At room temperature, a sample of tert-butyl N-[(3,5-difluoropyridine-2-carbonyl)amino]carbamate (1.7 g, 6.2 mmol) in dioxane (20 mL) was treated with 4 M hydrochloric acid (16 mL, 62 mmol). After completion of the reaction, the reaction mixture was quenched with aqueous NaHCO3 and extracted with EtOAc (3 × 50 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to afford the title compound as a white solid.

[0758] LC-MS (method C): 174 [M + H], Rt: 0.17 min

[0759] Step 4: Preparation of methyl 2-[2-(3,5-difluoropyridine-2-carbonyl)hydrazino]-2-oxoacetate

[0760] A solution of 3,5-difluoropyridine-2-carbohydrazide (2.0 g, 12 mmol) and TEA (4 mL, 29 mmol) in acetonitrile (20 mL) was cooled to 0 °C and treated dropwise with methyl oxalyl chloride (1.1 mL, 12 mmol). The reaction mixture was warmed to room temperature and stirred for 1 hour. Then the reaction mixture was diluted with water (50 ml) and extracted with EtOAc (2 × 75 ml). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to afford the title compound as a white solid.

[0761] LC-MS (method C): 259 [M + H], Rt: 0.15 min

[0762] Step 5: Preparation of methyl 5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazole-2-carboxylate

[0763]

[0764] A solution of methyl 2-[2-(3,5-difluoropyridine-2-carbonyl)hydrazino]-2-oxoacetate (0.5 g, 2 mmol) and phosphorus pentasulfide (0.1 mL) in toluene (5 mL) was refluxed for 3 h. After completion of the reaction, the reaction mixture was quenched with an aqueous solution of sodium acetate (1 g, 10 mmol) and extracted with EtOAc (2 × 40 ml). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel column chromatography (0 - 25% EtOAc in cyclohexane) to afford the title compound.

[0765] LC-MS (Method C): 258 [M+H], Rt: 0.99

[0766] 1 1H NMR (400 MHz, CDCl3) δ ppm: 4.10 (s, 3H) 7.48 (ddd, J = 9.66, 7.66, 2.31 Hz, 1H) 8.48 (d, J = 2.25 Hz, 1H)

[0767] Step 6: Preparation of 4-(1,5-dimethylpyrazol-4-yl)isoquinoline

[0768]

[0769] In a microwave vial, a suspension of 4-bromoisoquinoline (2.0 g, 9.4204 mmol), 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.3484 g, 10.362 mmol), and potassium carbonate (1.432 g, 10.36 mmol) in a toluene / methanol mixture (30 mL, 5:1) was degassed with argon for a few minutes and then tetra(triphenylphosphine)palladium(0) (0.545 g, 0.471 mmol) was added. Under microwave irradiation, the reaction mixture was heated at 100 °C and stirred for 1 h. After cooling to room temperature, the reaction mixture was partitioned between water and EtOAc and the organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash silica gel chromatography (eluting with EtOAc / 30% methanol) to give the title compound.

[0770] LCMS (Method A): m / z 225 [M+H], retention time 0.51 min

[0771] Step 7: Preparation of 4-(1,5-dimethylpyrazol-4-yl)-1,2,3,4-tetrahydroisoquinoline

[0772]

[0773] At room temperature, sodium cyanoborohydride (3.55 g, 53.7 mmol) was added to a solution of 4-(1,5-dimethylpyrazol-4-yl)isoquinoline (2.00 g, 8.96 mmol) in methanol (90 mL). The reaction mixture was stirred at room temperature and then hydrochloric acid (1.25 M, in methanol) was added until the pH reached 2 - 3. After stirring for 30 minutes at room temperature, the reaction mixture was diluted with water and basified with 2N sodium hydroxide, and the mixture was extracted with EtOAc (×3). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The resulting yellow oil was used without further purification.

[0774] LCMS (method A): m / z 228 [M+H]. Retention time 0.29 min

[0775] The hydrochloride salt of the title product (4-(1,5-dimethylpyrazol-4-yl)-1,2,3,4-tetrahydroisoquinoline; hydrochloride) can be obtained by treating the yellow oil with 2M HCl in ether and then concentrating in vacuo.

[0776] Step 8: Preparation of [5-(3,5-difluoro-2-pyridinyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol-4- yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-7, Table P)

[0777] A solution of methyl 5-(3,5-difluoro-2-pyridyl)-1,3,4-thiadiazole-2-carboxylate (0.05 g, 0.194 mmol, Example P1, Step 4) and 4-(1,5-dimethylpyrazol-4-yl)-1,2,3,4-tetrahydroisoquinoline (0.05 g, 0.233 mmol) in toluene (1 mL) was cooled to 0 °C. Then trimethylaluminum solution (2.0 mol / L) in toluene (0.29 mL) was carefully added dropwise, and the reaction mixture was kept at the same temperature for 10 min and then heated at 70 °C for 2 h. After completion of the reaction, the reaction mixture was slowly quenched with ice-cold brine solution (vigorous effervescence occurred). The resulting solution was extracted with EtOAc, and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by normal phase column chromatography (using 0 - 50% EtOAc in cyclohexane) to obtain the title compound

[0778] LC-MS (method C): 453 [M+H] Rt: 1.13 min

[0779] 11H NMR (400 MHz, CDCl3) δ ppm: 2.18 (s, 3H) 3.69 (s, 3H) 4.29 - 4.26 (m, 1H) 4.40 - 4.35 (m, 1H) 4.70 - 4.66 (m, 1H) 5.13 - 5.01 (m, 2H) 6.93 (s, 1H) 7.28 - 7.03 (m, 4H) 7.46 - 7.28 (m, 1H) 8.47 (m, 1H)

[0780] Example P3: Preparation of [5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol- 4-yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-8, Table P)

[0781] (Compound P - 8, Table P)

[0782] Step 1: Preparation of 2,6-difluoropyridine-3-carbonyl chloride

[0783]

[0784] The desired compound was prepared similarly to the example described in Step 1 of Example 2 from 2,6 - difluoropyridine - 3 - carboxylic acid and oxalyl chloride to obtain 2,6 - difluoropyridine - 3 - carbonyl chloride.

[0785] Step 2: Preparation of tert-butyl N-[(2,6-difluoropyridine-3-carbonyl)amino]carbamate

[0786]

[0787] The desired compound was prepared as previously described for Step 2 of Example 2 to obtain tert - butyl N - [(2,6 - difluoropyridine - 3 - carbonyl)amino]carbamate,

[0788] LC - MS (Method C): 174 [M + H - Boc], Rt: 0.43 min

[0789] Step 3: Preparation of 2,6-difluoropyridine-3-carbohydrazide

[0790]

[0791] A sample of tert - butyl N - [(2,6 - difluoropyridine - 3 - carbonyl)amino]carbamate (8.9 g, 31 mmol) was dissolved in 4 M hydrochloric acid in dioxane (77 mL, 310 mmol), and the reaction mixture was stirred overnight at room temperature. After completion, the reaction mixture was quenched with sodium bicarbonate and extracted with EtOAc (3 × 50 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to obtain the title compound as a pale yellow solid.

[0792] LC - MS (Method D): 174 [M + H] Rt: 0.23 min

[0793] 11H NMR (400 MHz, DMSO-d6) δ ppm: 4.63 (br s, 2H) 7.27 (d, J = 7.91 Hz, 1H) 8.32 (dt, J = 9.17, 8.07 Hz, 1H) 9.72 (br s, 1H)

[0794] Step 4: Preparation of methyl 2-[2-(2,6-difluoropyridine-3-carbonyl)hydrazino]-2-oxoacetate

[0795] A solution of 2,6-difluoropyridine-3-carbohydrazide (100 mg, 0.54 mmol) in DCM (1 mL) was cooled to 0 °C and TEA (0.19 mL, 1.37 mmol) was added, and the reaction mixture was treated dropwise with methyl oxalyl chloride (52.7 μL, 0.54 mmol). The reaction mixture was stirred at room temperature for 15 min, diluted with water (50 ml) and extracted with EtOAc (2 × 50 ml). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give a pale brown residue, which was then purified by combi flash using 40%-80% ethyl acetate in cyclohexane to afford methyl 2-[2-(2,6-difluoropyridine-3-carbonyl)hydrazino]-2-oxo-acetate as a pale yellow gummy substance.

[0796] LC-MS (method D): 260 [M+H], Rt: 0.22 min

[0797] Step 5: Preparation of methyl 5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazole-2-carboxylate

[0798]

[0799] A solution of methyl 2-[2-(2,6-difluoropyridine-3-carbonyl)hydrazino]-2-oxo-acetate (2.98 g, 10.3 mmol) in anhydrous THF (60 mL) was treated with Lawesson's reagent (4.75 g, 11.4 mmol), and the resulting reaction mixture was refluxed for 2 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude compound was purified by silica gel chromatography (using 0-50% EtOAc in cyclohexane) to afford the title compound

[0800] LC-MS (method D): 258 [M+H], Rt: 1.01 min

[0801] 1 1H NMR (400 MHz, CDCl3) δ ppm: 9.06 (td, J = 8.65, 7.40 Hz, 1H) 7.09-7.13 (m, 1H) 4.11 (s, 3H)

[0802] Step 6: Preparation of [5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazol-2-yl]-[4-(1,5-dimethylpyrazol-4- yl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-8, Table P)

[0803] A suspension of methyl 5-(2,6-difluoro-3-pyridyl)-1,3,4-thiadiazole-2-carboxylate (0.18 g, 0.665 mmol) and 4-(1,5-dimethyl-1H-pyrazol-1-ium-4-yl)-1,2,3,4-tetrahydroisoquinolin-2-ium; dichloride (0.2112 g, 0.798 mmol) in toluene (4 mL) was cooled to 0 °C. Then, trimethylaluminum solution (2.0 mol / L in toluene, 1.0 mL, 1.99 mmol) was carefully added dropwise, and the reaction mixture was maintained at the same temperature for 10 min and then heated to 90 °C for 2 h. After completion of the reaction, the reaction mixture was slowly quenched with ice-cold brine solution and extracted with EtOAc, and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was adsorbed onto diatomaceous earth and purified by reverse-phase column chromatography using (0 - 70% ACN in water) to obtain the pure compound as a mixture of enantiomers (60:40 ratio) as an off-white solid.

[0804] LC-MS (Method C): 453 [M+H] Rt: 1.13 min

[0805] 1 H NMR (400 MHz, CDCl3) δ ppm: 8.91 - 9.03 (m, 2H) 7.15 - 7.32 (m, 6H) 7.03 - 7.13 (m, 4H) 6.98 (s, 1H) 5.84 (d, J = 17.01 Hz, 1H) 5.42 (d, J = 16.76 Hz, 1H) 5.01 - 5.13 (m, 2H) 4.70 (dd, J = 12.51, 3.63 Hz, 1H) 4.44 (dd, J = 12.51, 5.00 Hz, 1H) 4.20 - 4.38 (m, 3H) 3.65 - 3.76 (m, 3H) 2.16 (s, 3H)

[0806] 19 F NMR (377 MHz, CDCl3) δ ppm: -61.81 (s, 1F) -61.84 (s, 1F) -64.24 (s, 1F) -64.27 (s, 1F)

[0807] Example P4: Preparation of [5-(2,6-difluoro-3-pyridinyl)-1,3,4-thiadiazol-2-yl]-[racemic-(1S,4S)-4- (1,5-dimethylpyrazol-4-yl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]methanone (Compound P-9, Table P) Preparation

[0808] (Compound P-9, Table P)

[0809] At ambient temperature, under an argon atmosphere, trimethylaluminum (2 M solution in toluene, 0.44 mL, 0.870 mmol) was added dropwise via syringe over a period of several minutes to a pale yellow suspension of (rac-1S,4S)-4-(1,5-dimethylpyrazol-4-yl)-1-methyl-1,2,3,4-tetrahydroisoquinoline (purity 70%, 0.150 g, 0.435 mmol) and methyl 5-(2,6-difluoro-3-pyridyl)-1,3,4-thiadiazole-2-carboxylate (0.118 g, 0.435 mmol) in toluene (1.74 mL). After the addition was complete, the reaction mixture was heated and stirred at 90 °C. After approximately 90', the mixture was cooled to room temperature and then 10 mL of 2 M aqueous NaOH was added. After dilution with water (30 mL), the mixture was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the crude product. The crude was purified by silica gel chromatography to give the title compound.

[0810] LC-MS (Method C): 467 [M+H] Rt: 1.18 min

[0811] Examples of the synthesized compounds of formula (I) are shown in Table P.

[0812] Table P: Synthesized compounds and spectroscopic and physicochemical data.

[0813]

[0814]

[0815]

[0816]

[0817]

[0818]

[0819]

[0820]

[0821]

[0822]

[0823]

[0824]

[0825] Biological Examples

[0826] Example B1: Alternaria solani / Tomato / Leaf Disc (Early Blight)

[0827] Tomato leaf discs of the cultivar Baby were placed on agar in a multi-well plate (24-well format) and sprayed with the formulated test compound diluted in water. Two days after application, the leaf discs were inoculated with a fungal spore suspension. The inoculated leaf discs were incubated in a climate chamber under a light regime of 12 h light / 12 h darkness, at 23 °C / 21 °C (day / night) and 80% rh, and the activity of the compound was evaluated as the percentage of disease control compared to untreated, when an appropriate level of disease damage appeared on the untreated test leaf discs (5 to 7 days after application).

[0828] When compared to untreated controls showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Alternaria solani at 200 ppm:

[0829] P-6, P-7, P-10, P-11, P-12, P-13, P-15, P-17, P-19, P-20, P-21, P-23, P-24, P-30, P-31, P-32, P-34, P-35, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45, P-51

[0830] Example B2: Botryotinia fuckeliana or Botrytis cinerea / Liquid culture (Botrytis cinerea disease) (Botrytis cinerea disease)

[0831] Fungal conidia from frozen storage were directly mixed into nutrient broth (Vogels broth). After placing the (DMSO) solution of the test compound in a microtiter plate (96-well format), nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and the inhibition of growth was determined photometrically 3 to 4 days after application.

[0832] When compared to untreated controls showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Botrytis fuckeliana at 20 ppm:

[0833] P-6, P-8, P-10, P-11, P-13, P-15, P-17, P-19, P-20, P-22, P-23, P-24, P-25, P-31, P-34, P-35, P-36, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45, P-50, P-51, P-52

[0834] Example B3: Glomerella lagenarium (Colletotrichum lagenarium) / Liquid culture (Anthracnose) (Colletotrichum lagenarium)

[0835] Fungal conidia from cryogenic storage were directly mixed into nutrient broth (PDB - potato dextrose broth). After placing the (DMSO) solution of the test compound into a microtiter plate (96 - well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and after 3 to 4 days of application, growth inhibition was measured photometrically.

[0836] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Glomerella cingulata at 20 ppm:

[0837] P - 6, P - 7, P - 8, P - 10, P - 11, P - 12, P - 13, P - 15, P - 17, P - 19, P - 20, P - 22, P - 23, P - 24, P - 25, P - 31, P - 34, P - 35, P - 36, P - 42, P - 43, P - 45, P - 50, P - 51, P - 52

[0838] Example B4: Blumeria graminis f. sp. tritici, Erysiphe graminis f. sp. tritici / Wheat / Leaf disc prophylaxis (Powdery mildew on wheat) (Powdery mildew on wheat)

[0839] Wheat leaf segments of cultivar Kanzler were placed on agar in a multi - well plate (24 - well format) and sprayed with formulated test compounds diluted in water. One day after application, leaf discs were inoculated by shaking powdery mildew - infected plants over these test plates. The inoculated leaf discs were incubated in a growth chamber at 20 °C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness, and the activity of the compounds was evaluated as the percentage of disease control compared to untreated controls when an appropriate level of disease damage appeared on the untreated control leaf segments (6 to 8 days after application).

[0840] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Blumeria graminis f. sp. tritici at 200 ppm:

[0841] P - 6, P - 10, P - 15, P - 17, P - 19, P - 20, P - 24, P - 31, P - 32, P - 34, P - 35, P - 38, P - 39, P - 40, P - 41, P - 42, P - 43, P - 44, P - 45

[0842] Example B5: Fusarium culmorum / Liquid culture (Fusarium head blight)

[0843] Fungal conidia from cryogenic storage were directly mixed into nutrient broth (PDB - Potato Dextrose Broth). After placing the (DMSO) solution of the test compound into a microtiter plate (96 - well format), nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and growth inhibition was determined photometrically 3 to 4 days after application.

[0844] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Fusarium culmorum at 20 ppm:

[0845] P - 6, P - 10, P - 11, P - 13, P - 15, P - 17, P - 20, P - 31, P - 34, P - 35, P - 39, P - 40, P - 42, P - 43, P - 45, P - 51, P - 52

[0846] Example B6: Fusarium culmorum / Wheat / Spikelet prophylaxis (Fusarium head blight)

[0847] Spikes of the wheat cultivar Monsun were placed on agar in a multi - well plate (24 - well format) and sprayed with formulated test compounds diluted in water. One day after application, the spikes were inoculated with a spore suspension of the fungus. The inoculated spikes were incubated in a climate chamber at 20 °C and 60% rh under a light regime of 72 h semi - darkness followed by 12 h light / 12 h darkness, and the activity of the compound was evaluated as the percentage of disease control compared to untreated when an appropriate level of disease damage appeared on the untreated test spikes (6 to 8 days after application).

[0848] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Fusarium culmorum at 200 ppm:

[0849] P - 6, P - 10, P - 15, P - 51

[0850] Example B7: Gibberella zeae (Fusarium graminearum) / Wheat / Spikelet prophylaxis (Fusarium head blight) (Fusarium head blight)

[0851] Spikes of the wheat cultivar Monsun were placed on agar in a multi - well plate (24 - well format) and sprayed with formulated test compounds diluted in water. One day after application, the spikes were inoculated with a spore suspension of the fungus. The inoculated test leaf discs were incubated in a climate chamber at 20 °C and 60% rh under a light regime of 72 h semi - darkness followed by 12 h light / 12 h darkness, and the activity of the compound was evaluated as the percentage of disease control compared to untreated when an appropriate level of disease damage appeared on the untreated test spikes (6 to 8 days after application).

[0852] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Fusarium graminearum at 200 ppm:

[0853] P-6, P-10, P-15, P-51

[0854] Example B8: Phaeosphaeria nodorum, Septoria nodorum / Wheat / Leaf disc prophylaxis (Septoria blotch) (Septoria blotch)

[0855] Wheat leaf segments of the cultivar Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with formulated test compounds diluted in water. Two days after application, the leaf discs were inoculated with a spore suspension of the fungus. The inoculated test leaf discs were incubated in a climate chamber under a 12 h light / 12 h dark light regime at 20 °C and 75% rh, and the activity of the compounds was evaluated as the percentage of disease control compared to untreated when an appropriate level of disease damage appeared on the untreated control leaf discs (5 to 7 days after application).

[0856] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Septoria nodorum at 200 ppm:

[0857] P-6, P-7, P-10, P-11, P-13, P-15, P-17, P-19, P-20, P-22, P-23, P-30, P-31, P-34, P-35, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45

[0858] Example B9: Cladosporium nivalis (Gerlachia nivalis) / Liquid culture (Cereal root rot)

[0859] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB - Potato Dextrose Broth). After placing the (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and the inhibition of growth was determined photometrically 4 to 5 days after application.

[0860] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Cladosporium nivalem at 20 ppm:

[0861] P-6, P-10, P-11, P-13, P-15, P-17, P-19, P-20, P-22, P-23, P-24, P-25, P-31, P-34, P-35, P-36, P-38, P-39, P-40, P-42, P-43, P-45, P-50, P-51

[0862] Example B10: Mycosphaerella arachidicola (Cercospora arachidicola) / Liquid culture (Early leaf spot) (Cercospora arachidicola)

[0863] Fungal conidia from cryogenic storage were directly mixed into nutrient broth (PDB - potato dextrose broth). After placing the (DMSO) solution of the test compound into a microtiter plate (96 - well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and growth inhibition was determined photometrically 4 to 5 days after application.

[0864] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Mycosphaerella arachidicola at 20 ppm:

[0865] P-6, P-7, P-8, P-10, P-11, P-12, P-13, P-15, P-17, P-19, P-20, P-22, P-23, P-24, P-30, P-31, P-34, P-35, P-36, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45, P-50, P-51, P-52

[0866] Example B11: Pyrenophora teres / Barley / Leaf disc prophylaxis (Net blotch)

[0867] Barley leaf segments of the cultivar Hasso were placed on agar in a multi - well plate (24 - well format) and sprayed with formulated test compounds diluted in water. Two days after application, the leaf segments were inoculated with a spore suspension of the fungus. The inoculated leaf segments were incubated in a growth chamber under a 12 h light / 12 h dark light regime at 20 °C and 65% rh, and the activity of the compound was evaluated as disease control compared to untreated controls when an appropriate level of disease damage appeared on the untreated control leaf segments (5 to 7 days after application).

[0868] When compared to untreated controls that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Pyrenophora teres at 200 ppm:

[0869] P-6, P-7, P-10, P-11, P-13, P-15, P-17, P-19, P-20, P-22, P-23, P-24, P-30, P-31, P-32, P-34, P-35, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45

[0870] Example B12: Sclerotinia sclerotiorum / Liquid culture (Cottony rot)

[0871] Mycelial fragments of a fresh growth liquid culture of the fungus were directly mixed into nutrient broth (PDB - potato dextrose broth). After placing a solution of the test compound in (DMSO) into a microtiter plate (96 - well format), nutrient broth containing the fungal material was added. The test plates were incubated at 24 °C and the inhibition of growth was determined photometrically 3 to 4 days after application.

[0872] When compared to an untreated control that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Sclerotinia sclerotiorum at 20 ppm:

[0873] P-6, P-15, P-35, P-39, P-43, P-51

[0874] Example B13: Mycosphaerella graminicola (Septoria tritici) / Liquid culture (Septoria blotch) (Septoria blotch)

[0875] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB - potato dextrose broth). After placing a solution of the test compound in (DMSO) into a microtiter plate (96 - well format), nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and the inhibition of growth was determined photometrically 4 to 5 days after application.

[0876] When compared to an untreated control that showed extensive disease development under the same conditions, the following compounds gave at least 80% control of Mycosphaerella graminicola at 20 ppm:

[0877] P-1, P-6, P-7, P-8, P-10, P-11, P-12, P-13, P-15, P-17, P-19, P-20, P-22, P-23, P-24, P-25, P-30, P-31, P-34, P-35, P-36, P-38, P-39, P-40, P-41, P-42, P-43, P-44, P-45, P-50, P-51, P-52, P-56 Example B14: Puccinia recondita f. sp. tritici / Wheat / Leaf disc treatment (Brown rust)

[0878] The wheat leaf segments of cultivar Kanzler were placed on agar in a multiwell plate (24-well format). The leaf segments were inoculated with a spore suspension of the fungus. The plates were stored in the dark at 19 °C and 75% rh. One day after inoculation, the formulated test compound diluted in water was applied. The leaf segments were incubated at 19 °C and 75% rh in a climate chamber under a 12 h light / 12 h dark light regime, and the activity of the compound was evaluated as the percentage of disease control compared to the untreated, when an appropriate level of disease damage appeared on the untreated test leaf segments (6 to 8 days after application).

[0879] When compared to an untreated control showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Puccinia recondita f. sp. tritici at 200 ppm:

[0880] P-29

[0881] Example B15: Puccinia recondita f. sp. tritici / Wheat / Leaf disc prophylaxis (Brown rust)

[0882] Wheat leaf segments of cultivar Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. One day after application, the leaf discs were inoculated with a spore suspension of the fungus. The inoculated leaf segments were incubated at 19 °C and 75% rh in a climate chamber under a 12 h light / 12 h dark light regime, and the activity of the compound was evaluated as the percentage of disease control compared to the untreated, when an appropriate level of disease damage appeared in the untreated test leaf segments (7 to 9 days after application).

[0883] When compared to an untreated control showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Puccinia recondita f. sp. tritici at 200 ppm:

[0884] P-11, P-19, P-20, P-42

[0885] Example B16: Magnaporthe grisea (Pyricularia oryzae) / Liquid culture (Rice blast)

[0886] The fungal conidia from frozen storage were directly mixed into nutrient broth (PDB - Potato Dextrose Broth). After placing the (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24 °C and the inhibition of growth was determined photometrically 3 to 4 days after application.

[0887] When compared to an untreated control showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Magnaporthe oryzae at 20 ppm:

[0888] P-6, P-10, P-31, P-34, P-35, P-36, P-38, P-39, P-40, P-42, P-43, P-45, P-51, P-52

[0889] Example B17: Magnaporthe grisea (Pyricularia oryzae) / Rice / Leaf disc prophylaxis (Rice blast) (Rice blast)

[0890] The rice leaf segment cultivar Ballila was placed on agar in a multi-well plate (24-well format) and sprayed with a formulated test compound diluted in water. Two days after application, the leaf segments were inoculated with a spore suspension of the fungus. In a climate chamber, the inoculated leaf segments were incubated at 22 °C and 80% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness, and the activity of the compound was evaluated as the percentage of disease control compared to untreated, when an appropriate level of disease damage appeared in the untreated test leaf segments (5 to 7 days after application).

[0891] When compared to untreated controls showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Magnaporthe oryzae at 200 ppm:

[0892] P-38, P-39, P-40, P-41, P-42, P-43, P-45

[0893] Example B18: Rhizoctonia solani / Liquid culture (Root rot, damping-off)

[0894] Mycelial fragments of a fresh liquid culture of the fungus were directly mixed into nutrient broth (PDB - potato dextrose broth). After placing a (DMSO) solution of the test compound in a microtiter plate (96-well format), the nutrient broth containing the fungal material was added. The test plates were incubated at 24 °C and growth inhibition was determined photometrically 3 to 4 days after application.

[0895] When compared to untreated controls showing extensive disease development under the same conditions, the following compounds gave at least 80% control of Rhizoctonia solani at 20 ppm:

[0896] P-11, P-15, P-20.

Claims

1. A compound of formula (I) or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof wherein R 1 selected from hydrogen, C1-C 4- alkyl, C2-C 4- alkenyl, C2-C4-alkynyl, or C3-C6 cycloalkyl; R 2 selected from hydrogen, halogen, C1-C 4- alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C 4- alkylcarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbonimino, N-hydroxy-C-C1-C4-alkyl-carbonimino, or C1-C 4- alkoxycarbonyl; R 3 selected from hydrogen, a halogen, a C1-C4 haloalkyl, or a C1-C4 alkyl; R 4 selected from hydrogen, a halogen, a C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, or a C1-C4 alkyl group; R 5 and R 6 are independently selected from hydrogen, or C1-C4-alkyl; R 7 selected from hydrogen, C1-C4 alkyl, C1-C4 alkylcarbonyl, N-C1-C4 alkoxy-C-C1-C4 alkyl-carbonimino, N-hydroxy-C-C1-C 4- alkyl-carbonimino, C1-C4 alkoxycarbonyl, N-methoxy-N-methyl-carbonyl, C1-C4 alkylaminocarbonyl, di(C1-C4 alkyl)aminocarbonyl, phenyl, a 5- or 6-membered heteroaryl, or a C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryls contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, provided that not more than one is O or S; and wherein any one of the phenyl and the 5- or 6-membered heteroaryls is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, cyano, carboxyl, C1-C4 alkyl, or C1-C4 alkoxy; and wherein the C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, cyano, C1-C4 alkyl, or C1-C4 alkoxy; B 1 selected from CR 10 or N; B 2 selected from CR 11 or N; R 8 、R 9 、R 10 and R 11 are independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkoxy-C1-C4 alkyl, N-C1-C4 alkylamino, N,N-bis(C1-C4 alkyl)amino, C1-C4 alkoxycarbonyl, C1-C4 alkylcarbonyl, N-C1-C4 alkoxy-C1-C4 alkyl-carbodiimide, N-hydroxy-C1-C4 alkyl-carbodiimide, hydroxy, trifluoromethylsulfonyloxy, cyano, carboxy, amino, phenyl, 5- or 6-membered heteroaryl or C3-C6 cycloalkyl; wherein any one of said 5- or 6-membered heteroaryls contains 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, provided that no more than one is O or S; and wherein any one of said phenyl, 5- or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy; A 1 , A 2 and A 3 Independently selected from CR 12 , N, NR 13 , O or S, provided that A 1 , A 2 and A 3 At least one of is selected from N, O or S, and A 1 , A 2 and A 3 No more than one of them is O or S; R 12 、R 13 are independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, or C2-C4 alkynyl; and Z 1 a 6-membered heteroaryl selected from those containing 1 or 2 heteroatoms selected from N; wherein any one of said 6-membered heteroaryls is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-C4 haloalkyl, cyano, C1-C4 alkyl, C2-C4 alkynyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, or C1-C4 alkylsulfonyl.

2. The compound having the formula (I) according to claim 1, wherein, R 1 is methyl and R 3 is hydrogen.

3. The compound of formula (I) according to claim 1 or claim 2, wherein, R 2 is hydrogen, chlorine, or methyl.

4. A compound having the formula (I) according to any one of claims 1 to 3, wherein, R 4 is hydrogen or methyl, and R 5 and R 6 is hydrogen.

5. A compound having the formula (I) according to any one of claims 1 to 4, wherein, R 7 is hydrogen, a C1-C4 alkyl group, or a C3-C6 cycloalkyl group.

6. A compound having the formula (I) according to any one of claims 1 to 5, wherein, B 1 is CR 10 and B 2 is CR 11 , and wherein, R 10 and R 11 are independently selected from hydrogen, bromine, chlorine, or cyano group.

7. A compound having the formula (I) according to any one of claims 1 to 6, wherein, R 8 is hydrogen, bromine, chlorine, or cyano, and wherein R 9 is hydrogen, bromine, chlorine, cyano, methyl or methoxy.

8. A compound having the formula (I) according to any one of claims 1 to 7, wherein, Z 1 selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazin-2-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, or pyrimidin-5-yl; wherein any one of the pyridyl-, pyrazin-, pyridazin- or pyrimidin- moieties is unsubstituted or substituted with 1 or 2 substituents selected from fluorine.

9. The compound of formula (I) according to claim 8, wherein, Z 1 selected from 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 6-fluoro-2-pyridyl, 3,4-difluoro-2-pyridyl, 3,5-difluoro-2-pyridyl, 2-fluoro-4-pyridyl, 5-fluoropyrimidin-4-yl, 5-fluoropyrimidin-2-yl, 4-fluoropyridazin-3-yl, 5-fluoropyridazin-3-yl, 4,5-difluoropyridazin-3-yl, or 5-fluoropyridazin-4-yl.

10. A compound of formula (I-A): wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、B 1 、B 2 and Z 1 correspond to the same definitions as for the compounds of formula (I) according to any one of claims 1 to 9, and A is selected from wherein indicates a bond to the C(=O) group and the arrow indicates a bond to the Z 1 group, and wherein R 14a is selected from hydrogen or C1-C4 alkyl.

11. A compound having the formula (I-A) according to claim 10, wherein, A is selected from: wherein indicates a bond to the C(=O) group and the arrow indicates a bond to the Z 1 group, and wherein R 14a is hydrogen.

12. A compound of formula (IIb-1) wherein R 0 is a C1-C6-alkyl; Z 1 is as defined for a compound of formula (I) according to any one of the preceding claims; and A is selected from A1 to A36 wherein indicates a bond to the C(=O) group and the arrow indicates a bond to the Z 1 group, and wherein R 12a , R 13a , R 14a , R 12b , R 13b and R 14b are independently selected from hydrogen, C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl.

13. An agrochemical composition comprising a fungicidally effective amount of a compound of formula (I) as described in any one of claims 1 to 9 or a compound of formula (I-A) as described in any one of claims 10 to 11.

14. The agrochemical composition according to claim 13, wherein the agrochemical composition further comprises at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

15. A method for controlling or preventing useful plants from being infected by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula (I) as described in any one of claims 1 to 9 or a compound of formula (I-A) as described in any one of claims 10 to 11 or a composition comprising the compound of formula (I) or the compound of formula (I-A) is applied to the plants, parts thereof or the site thereof.

16. Use of a compound as described in any one of claims 1 to 11 as a fungicide.

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