Pyridine compounds for use in combating dihydroorotate dehydrogenase inhibitor resistant phytopathogenic fungi

Abstract

The present invention relates to the use of a compound (I) wherein the variables are as defined in the claims and the description for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi, and to a method for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi wherein the variables are as defined in the claims and the description, and to a method for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi, the method comprises treating these phytopathogenic fungi or materials, plants, soil or seeds infected or infected by or at risk of being infected or infected by said phytopathogenic fungi with at least one compound (I). In addition, the invention also relates to a mutant DHODH inhibitor resistant DHODH enzyme and a nucleic acid molecule comprising at least one nucleotide sequence encoding the mutant DHODH enzyme. # imgabs0 #

Description

[0001] The present invention relates to the use of a compound (I) as defined below for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi, and to a method for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi, which method comprises treating these phytopathogenic fungi or materials, plants, soil or seeds infected or infested by, or at risk of being infected or infested by, said phytopathogenic fungi with at least one compound (I) as defined below. Furthermore, the present invention also relates to a mutant DHODH inhibitor-resistant DHODH enzyme and a nucleic acid molecule comprising at least one nucleotide sequence encoding the mutant DHODH enzyme. Background Art

[0002] Dihydroorotate dehydrogenase (DHODH; PyrE) is an enzyme involved in de novo pyrimidine synthesis that catalyzes the oxidation of dihydroorotate to orotate. Depending on the differences in amino acid sequence, DHODH is divided into two classes; class II DHODH is present in most fungi (including Aspergillus fumigatus and Candida albicans), animals, plants, Gram-negative bacteria and archaea. These use the FMN molecule as a cofactor, and in the case of humans and fungi, this is by means of oxidation recycling via a quinone cofactor from the respiratory chain. The human and fungal proteins are non-covalently associated with the inner mitochondrial membrane via an N-terminal transmembrane domain. The quinone-binding pocket is adjacent to but distinct from the catalytic site of the enzyme. Class I enzymes are present in Gram-positive bacteria, trypanosomes, Saccharomyces cerevisiae and closely related fungi (such as other members of the genus Saccharomyces).

[0003] Although DHODH proteins have been described as potential antifungal targets for the medical treatment of fungal infections (see, for example, WO 2009 / 133379), their suitability as targets against plant pathogens has not been described.

[0004] The inventors have observed that the application of several known plant pathogen inhibitors leads to the selection of plant pathogen mutants that are resistant to such inhibitors. They have observed that the resistance is caused by a mutant DHODH gene of the pathogen.

[0005] A first object of the present invention is to identify novel species of phytopathogenic fungi, in particular mutant strains containing a mutant form of their endogenous DHODH gene and showing resistance against several prior art antifungal agents, in particular quinoline-type antifungal compounds. Such mutant strains or mutant DHODH enzymes can be used as targets for the identification of suitable and effective plant pathogen inhibitors.

[0006] Another object of the present invention is to provide DHODH inhibitor compounds which are suitable for combating such mutant phytopathogenic fungi that are resistant to such prior art plant pathogen inhibitors. Summary of the Invention

[0007] This object is achieved by using pyridine compounds of formula (I) as defined below.

[0008] Accordingly, in a first aspect, the present invention relates to the use of a compound of formula (I) or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi

[0009]

[0010] wherein

[0011] R 1 is hydrogen, halogen, CN, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

[0012] R 2 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyloxy or C 2 -C 6 -alkynyloxy;

[0013] R 3 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6-haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyloxy or C 2 -C 6 -alkynyloxy;

[0014] R 4 is hydrogen, halogen, CN, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

[0015] R 5 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, where the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 5a ; where

[0016] each R 5a independently is halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy;

[0017] R 6 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 6a ; wherein

[0018] each R 6a independently is halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy;

[0019] or

[0020] R 5 and R 6 together form an oxo group (=O);

[0021] or

[0022] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing 1, 2 or 3 heteroatoms selected from O and S as ring members; wherein the carbocyclic or heterocyclic ring is unsubstituted or carries 1, 2 or 3 substituents R 56 ; wherein

[0023] each R 56 independently is halogen, C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl;

[0024] R 7 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 7a ; wherein

[0025] Each R 7a is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy;

[0026] R 8 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 8a ; wherein

[0027] each R 8a is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy;

[0028] or

[0029] R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing 1, 2 or 3 heteroatoms selected from O and S as ring members;

[0030] Each X is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy or C 1 -C6 - haloalkoxy;

[0031] Y is O when m is 1; and is O or NR when m is 0 9 ;

[0032] where

[0033] R 9 is hydrogen, CN, CH 2 CN, CH(CH 3 )CN, CH(=O), -C(=O)C 1 -C 6 - alkyl, -C(=O)C 2 -C 6 - alkenyl, -C(=O)C 2 -C 6 - alkynyl, -C(=O)C 3 -C 6 - cycloalkyl, -C(=O)-N(H)C 1 -C 4 - alkyl, -C(=O)-N(C 1 -C 4 - alkyl) 2、 C 1 -C 6 - alkyl, C 1 -C 6 - alkoxy, C 1 -C 4 - haloalkyl, C 3 -C 6 - cycloalkyl, C 3 -C 6 - halocycloalkyl, C 2 -C 6 - alkenyl, C 2 -C 6 - haloalkenyl, C 2 -C 6 - alkynyl, C 2 -C 6 - haloalkynyl, -S(=O) 2 -R 9a、 a five - or six - membered heteroaryl, aryl or benzyl; where the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O and S as ring members; where the benzene rings in the aryl and benzyl are unsubstituted or carry 1, 2, 3, 4 or 5 substituents selected from the group consisting of: CN, halogen, OH, C 1 -C 4 - alkyl, C 1 -C 4 - haloalkyl, C 1 -C 4-alkoxy and C 1 -C 4 -haloalkoxy; wherein the benzene ring in benzyl is unsubstituted or bears 1, 2 or 3 substituents selected from the group consisting of: CN and halogen;

[0034] wherein

[0035] R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the benzene ring in the last two mentioned groups is unsubstituted or bears 1, 2 or 3 substituents each independently selected from the group consisting of: halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl and C 2 -C 6 -haloalkynyl;

[0036] m is 0 or 1; and

[0037] n is 0, 1, 2 or 3.

[0038] The present invention further relates to a method for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi, which method comprises treating these phytopathogenic fungi or materials, plants, soil or seeds infected or infested with or at risk of being infected or infested with said phytopathogenic fungi with an effective amount of at least one compound of formula I, its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt or with a composition comprising at least one compound of formula I, its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt.

[0039] In particular, the method comprises

[0040] a) identifying a phytopathogenic fungus as defined above or below, or a material, plant, soil or seed at risk of being diseased by a phytopathogenic fungus as defined above or below,

[0041] and

[0042] b) treating the fungus or the material, plant, soil or seed with an effective amount of at least one compound of formula I as defined above or below, or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt, or with an effective amount of a composition comprising at least one compound of formula I as defined above or below, or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt.

[0043] Furthermore, the present invention also relates to the use of an agrochemical composition comprising at least one compound of formula I as defined above or below, its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt, and at least one adjuvant, for combating dihydroorotate dehydrogenase inhibitor-resistant phytopathogenic fungi as defined above or below.

[0044] Furthermore, the present invention also relates to novel DHODH mutants, corresponding coding sequences and organisms carrying them, which mutants are defined in more detail below. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 Shows a sequence alignment of the endogenous DHODH of a set of phytopathogenic fungi. The top row shows the native amino acid sequence of Botrytis cinerea DHODH (long version SEQ ID NO: 1). Similar amino acid sequence positions can be readily derived therefrom. For example, the amino acid sequence position V181 of Alternaria alternata DHODH (SEQ ID NO: 3) depicted in the second row of the alignment is similar to position V195 of Botrytis cinerea DHODH (long version SEQ ID NO: 1).

[0046] Figure 2 shows the results of modeling different inhibitor molecules into the substrate pocket of Botrytis cinerea DHODH (native enzyme and V195F mutant). Figure 2a Shows the modeling results of prior art quinoline-type inhibitors of the native enzyme (left) and mutant V195F (right), in particular the steric hindrance induced by the larger phenyl residue in position 195. On the other hand, Figure 2b illustrates that the pyridine-type residue of the inhibitor of the present invention fits better into the substrate pocket of the V195F mutant and thus allows combating the V195F mutant resistant to prior art quinoline-type inhibitors. DETAILED DESCRIPTION

[0047] General definition

[0048] The organic moieties mentioned in the above definitions of variables, like the term halogen, are general terms for separate lists of individual group members. The prefix C n -C m indicates the possible number of carbon atoms in the group in each case.

[0049] The term halogen represents fluorine, bromine, chlorine or iodine in each case.

[0050] The term "alkyl", as used as such and in the alkyl moieties of alkoxy, alkylcarbonyl, etc., is a saturated straight-chain or branched-chain aliphatic hydrocarbon group usually having 1 to 6 ("C 1 -C 6 -alkyl"), 1 to 4 ("C 1 -C 4 -alkyl"), 1 to 3 ("C 1 -C 3 -alkyl") or 1 or 2 ("C 1 -C 2 -alkyl") carbon atoms. "C 1 -C 2 -alkyl" is a saturated aliphatic hydrocarbon group having 1 or 2 carbon atoms. "C 1 -C 3 -alkyl" is a saturated straight-chain or branched-chain aliphatic hydrocarbon group having 1 to 3 carbon atoms. "C 1 -C 4 -alkyl" is a saturated straight-chain or branched-chain aliphatic hydrocarbon group having 1 to 4 carbon atoms. "C 1 -C 6 -alkyl" is a saturated straight-chain or branched-chain aliphatic hydrocarbon group having 1 to 6 carbon atoms. C 1 -C 2 -alkyl is methyl or ethyl. Except for those mentioned for C 1 -C 2 -alkyl, examples of C 1 -C 3 -alkyl also include propyl and isopropyl. Except for those mentioned for C 1 -C 3 -alkyl, examples of C 1 -C 4 -alkyl also include butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl) or 1,1-dimethylethyl (tert-butyl). Except for those mentioned for C 1 -C 4 -alkyl, examples of C 1 -C 6Examples of -alkyl also include pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, hexyl, 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.

[0051] The term "haloalkyl", as used as such and in the haloalkyl moiety of haloalkoxy groups etc., is also denoted as "halogenoalkyl" or "partially or fully halogenated alkyl", indicating a saturated straight-chain or branched aliphatic hydrocarbon group generally having 1 to 6 ("C 1 -C 6 -halo(halogeno)alkyl"), 1 to 4 ("C 1 -C 4 -halo(halogeno)alkyl"), 1 to 3 ("C 1 -C 3 -halo(halogeno)alkyl") or 1 or 2 ("C 1 -C 2 -halo(halogeno)alkyl") carbon atoms, some or all of the hydrogen atoms in which are replaced by halogen atoms as mentioned above, especially fluorine, chlorine and / or bromine. "C 1 -C 2 -haloalkyl" refers to an alkyl group having 1 or 2 carbon atoms (as mentioned above), some or all of the hydrogen atoms in which are replaced by halogen atoms as mentioned above, especially fluorine, chlorine and / or bromine. "C 1 -C 3 -haloalkyl" refers to a straight-chain or branched alkyl group having 1 to 3 carbon atoms (as mentioned above), some or all of the hydrogen atoms in which are replaced by halogen atoms as mentioned above, especially fluorine, chlorine and / or bromine. "C 1 -C 4 -haloalkyl" refers to a straight-chain or branched alkyl group having 1 to 4 carbon atoms (as mentioned above), some or all of the hydrogen atoms in which are replaced by halogen atoms as mentioned above, especially fluorine, chlorine and / or bromine. "C 1 -C 6 -haloalkyl" refers to a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as mentioned above), some or all of the hydrogen atoms in which are replaced by halogen atoms as mentioned above, especially fluorine, chlorine and / or bromine. C 1 -C 2Examples of haloalkyl groups are chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 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 or pentafluoroethyl. Except for those mentioned for C 1 -C 2 -haloalkyl, examples of C 1 -C 3 -haloalkyl also include 1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 1,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, heptafluoropropyl, 1,1,1-trifluoropropan-2-yl, 3-chloropropyl, etc. Except for those mentioned for C 1 -C 3 -haloalkyl, examples of C 1 -C 4 -haloalkyl also include 4-chlorobutyl, etc.

[0052] Strictly speaking, the term "alkenyl" refers to a straight-chain or branched-chain aliphatic hydrocarbon group that is mono-unsaturated (i.e., contains one C-C double bond), which usually has 2 to 6 ("C 2 -C 6 -alkenyl"), 2 to 4 ("C 2 -C 4 -alkenyl") or 2 to 3 ("C 2 -C 3 -alkenyl") carbon atoms, where the C-C double bond can be at any position. However, as used in the present invention, the term also encompasses "polyalkenyl" groups, i.e., straight-chain or branched-chain aliphatic hydrocarbon groups that usually have 4 to 6 ("C 4 -C 6 -polyalkenyl") carbon atoms and two or three conjugated or separated but not cumulative C-C double bonds. Examples of C 2 -C 3 -alkenyl (only 1 C-C double bond) in the strict sense are vinyl, 1-propenyl, 2-propenyl or 1-methylethenyl. Examples of C 2 -C 4 -alkenyl (only 1 C-C double bond) in the strict sense are vinyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl and 2-methyl-2-propenyl. Examples of C 2 -C 6Examples of alkenyl (with only one C-C double bond) are vinyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl, 1-ethyl-2-methyl-2-propenyl, etc. Examples of polyenyl are buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, penta-1,3-dien-1-yl, penta-1,3-dien-2-yl, penta-1,3-dien-3-yl, penta-1,3-dien-4-yl, penta-1,3-dien-5-yl, penta-1,4-dien-1-yl, penta-1,4-dien-2-yl, penta-1,4-dien-3-yl, etc.

[0053] As used herein, the term "haloalkenyl" is also denoted as "halogenoalkenyl" or "partially or fully halogenated alkenyl", and refers to an unsaturated straight-chain or branched hydrocarbon group having 2 to 3 ("C 2 -C 3 -halo(halogen)alkenyl"), 2 to 4 ("C 2 -C 4 -halo(halogen)alkenyl") or 2 to 6 ("C 2 -C 6 -halo(halogen)alkenyl") carbon atoms and a double bond at any position (as mentioned above), wherein some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above, particularly fluorine, chlorine and bromine. Examples are vinyl chloride group, chloroallyl group, etc.

[0054] As used herein, the term "alkynyl" refers to a straight-chain or branched hydrocarbon group having 2 to 3 ("C 2 -C 3 -alkynyl"), 2 to 4 ("C 2 -C 4 -alkynyl") or 2 to 6 ("C 2 -C 6 -alkynyl") carbon atoms and one or two triple bonds at any position, such as C 2 -C 3 -alkynyl, such as ethynyl, 1-propynyl or 2-propynyl; C 2 -C 4 -alkynyl, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, etc.; C 2 -C 6-Alkynyl groups, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl, and the like.

[0055] As used herein, the term "haloalkynyl" is also denoted as "halogen alkynyl" or "partially or fully halogenated alkynyl", and refers to an unsaturated straight-chain or branched hydrocarbon group having 2 to 3 ("C 2 -C 3 -halo(halogen)alkynyl"), 2 to 4 ("C 2 -C 4 -halo(halogen)alkynyl"), or 2 to 6 ("C 2 -C 6 -halo(halogen)alkynyl") carbon atoms and one or two triple bonds (as mentioned above) at any position, wherein some or all of the hydrogen atoms in these groups are replaced by halogen atoms as mentioned above, particularly fluorine, chlorine, and bromine.

[0056] As used herein, the term "cycloalkyl" refers to a monocyclic saturated hydrocarbon group having 3 to 6 carbon atoms ("C 3 -C 6 -cycloalkyl"). Examples are cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0057] As used herein, the term "halocycloalkyl" is also denoted as "halogen cycloalkyl" or "partially or fully halogenated cycloalkyl", and refers to a group having 3 to 6 ("C 3 -C 6"-Halogenated (halo) cycloalkyl") is a monocyclic saturated hydrocarbon group of carbon ring members (mentioned above), where some or all of the hydrogen atoms are replaced by halogen atoms (especially fluorine, chlorine, and bromine) as mentioned above. Halogenated cycloalkyls are, for example, 1-fluorocyclopropyl, 2-fluorocyclopropyl, 1-chlorocyclopropyl, 2-chlorocyclopropyl, 1,1-difluorocyclopropyl, 1,2-difluorocyclopropyl, 2,2-difluorocyclopropyl, 1,1,2,2-tetrafluorocyclopropyl, etc.

[0058] "Alkoxy" is also expressed as "O-alkyl" and is an alkyl group as defined above attached to the rest of the molecule via an oxygen atom. "C 1 -C 2 -Alkoxy" is a C 1 -C 2 -alkyl group attached via an oxygen atom. "C 1 -C 3 -Alkoxy" is a C 1 -C 3 -alkyl group attached via an oxygen atom. "C 1 -C 4 -Alkoxy" is a C 1 -C 4 -alkyl group attached via an oxygen atom. "C 1 -C 6 -Alkoxy" is a C 1 -C 6 -alkyl group attached via an oxygen atom. C 1 -C 2 -Alkoxy is methoxy or ethoxy. C 1 -C 3 -Alkoxy is additionally, for example, n-propoxy and 1-methylethoxy (isopropoxy). C 1 -C 4 -Alkoxy is additionally, for example, butoxy, 1-methylpropoxy (sec-butoxy), 2-methylpropoxy (isobutoxy), or 1,1-dimethylethoxy (tert-butoxy). C 1 -C 6-The alkoxy group is further, for example, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy.

[0059] "Halogenated alkoxy group" is also expressed as "haloalkoxy group" or "O-haloalkyl group", and is a halogenated alkyl group as defined above attached to the rest of the molecule via an oxygen atom. "C 1 -C 2 -Halogenated (halo) alkoxy group" is a C 1 -C 2 -Halogenated alkyl group attached via an oxygen atom. "C 1 -C 3 -Halogenated (halo) alkoxy group" is a C 1 -C 3 -Halogenated alkyl group attached via an oxygen atom. "C 1 -C 4 -Halogenated (halo) alkoxy group" is a C 1 -C 4 -Halogenated alkyl group attached via an oxygen atom. "C 1 -C 6 -Halogenated (halo) alkoxy group" is a C 1 -C 6 -Halogenated alkyl group attached via an oxygen atom. C 1 -C 2 -Halogenated alkoxy group is, for example, OCH 2 F, OCHF 2 、OCF 3 、OCH 2 Cl, OCHCl 2 、OCCl 3 、Chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxycarbonyl, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy or OCF 2 F 5 。C1 -C 3 -The haloalkoxy group is further, for example, 2-fluoropropoxy, 3-fluoropropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromopropoxy, 3,3,3-trifluoropropoxy, 3,3,3-trichloropropoxy, OCH 2 -C 2 F 5 、OCF 2 -C 2 F 5 、1-(CH 2 F)-2-fluoroethoxy, 1-(CH 2 Cl)-2-chloroethoxy or 1-(CH 2 Br)-2-bromoethoxy. C 1 -C 4 -The haloalkoxy group is further, for example, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy or nonafluorobutoxy. C 1 -C 6 -The haloalkoxy group is further, for example, 5-fluoropentoxy, 5-chloropentoxy, 5-bromopentoxy, 5-iodopentoxy, undecafluoropentoxy, 6-fluorohexoxy, 6-chlorohexoxy, 6-bromohexoxy, 6-iodohexoxy or dodecafluorohexoxy.

[0060] "Alkenyloxy" is also expressed as "O-alkenyl", and is an alkenyl group as defined above attached to the rest of the molecule via an oxygen atom. "C 2 -C 3 -Alkenyloxy" is a C 2 -C 3 -alkenyl group as defined above attached via an oxygen atom. "C 2 -C 4 -Alkenyloxy" is a C 2 -C 4 -alkenyl group as defined above attached via an oxygen atom. "C 2 -C 6 -Alkenyloxy" is a C 2 -C 6 -alkenyl group as defined above attached via an oxygen atom. C 2 -C 3 -Examples of C 2 -C 3 -alkenyloxy are vinyloxy, prop-1-en-1-yloxy, prop-1-en-2-yloxy or prop-1-en-3-yloxy. In addition to those mentioned above for C 2 -C 4Examples of -alkenyloxy are also but-1-en-1-yloxy, but-2-en-1-yloxy, but-3-en-1-yloxy, 1-methylprop-1-en-1-yloxy, 2-methylprop-1-en-1-yloxy, 1-methylprop-2-en-1-yloxy or 2-methylprop-2-en-1-yloxy.

[0061] "Halogenalkenyloxy" is also denoted as "haloalkenyloxy" or "O-haloalkenyl", and is a haloalkenyl group as defined above attached to the remainder of the molecule via an oxygen atom. "C 2 -C 3 -halo(halogen)alkenyloxy" is a C 2 -C 3 -haloalkenyl group attached via an oxygen atom. "C 2 -C 4 -halo(halogen)alkenyloxy" is a C 2 -C 4 -haloalkenyl group attached via an oxygen atom. "C 2 -C 6 -halo(halogen)alkenyloxy" is a C 2 -C 6 -haloalkenyl group attached via an oxygen atom.

[0062] "Alkynyloxy" is also denoted as "O-alkynyl", and is an alkynyl group as defined above attached to the remainder of the molecule via an oxygen atom. "C 2 -C 3 -alkynyloxy" is a C 2 -C 3 -alkynyl group attached via an oxygen atom. "C 2 -C 4 -alkynyloxy" is a C 2 -C 4 -alkynyl group attached via an oxygen atom. "C 2 -C 6 -alkynyloxy" is a C 2 -C 6 -alkynyl group attached via an oxygen atom. C 2 -C 3 -alkynyloxy examples are ethynyloxy, prop-1-yn-1-yloxy, prop-1-yn-2-yloxy or prop-1-yn-3-yloxy. In addition to those mentioned above for C 2 -C 3 -alkynyloxy, C 2 -C 4Examples of -alkynyloxy groups are also but-1-yn-1-yloxy, but-2-yn-1-yloxy, but-3-yn-1-yloxy, 1-methylprop-1-yn-1-yloxy, 2-methylprop-1-yn-1-yloxy, 1-methylprop-2-yn-1-yloxy or 2-methylprop-2-yn-1-yloxy.

[0063] "Halogenated alkynyloxy" is also denoted as "haloalkynyloxy" or "O-haloalkynyl", and is a haloalkynyl group as defined above attached to the remainder of the molecule via an oxygen atom. "C 2 -C 3 -halogenated (halo) alkynyloxy" is a C 2 -C 3 -haloalkynyl group attached via an oxygen atom. "C 2 -C 4 -halogenated (halo) alkynyloxy" is a C 2 -C 4 -haloalkynyl group attached via an oxygen atom. "C 2 -C 6 -halogenated (halo) alkynyloxy" is a C 2 -C 6 -haloalkynyl group attached via an oxygen atom.

[0064] Oxo is the group =O, i.e., the CH 2 group is replaced by C=O.

[0065] R 5 and R 6 together with the carbon atom to which they are attached can form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing 1, 2 or 3 heteroatoms selected from O and S as ring members. This ring is spiro-linked to the fused ring system to which R 5 and R 6 are attached, and the carbon atom to which R 5 and R 6 are attached is the spiro atom. The ring is usually monocyclic.

[0066] Examples of saturated three- to six-membered monocyclic carbon rings formed by R 5 and R 6 together with the carbon atom to which they are attached are cyclopropane-1,1-diyl, cyclobutane-1,1-diyl, cyclopentane-1,1-diyl or cyclohexane-1,1-diyl.

[0067] Examples of R 5 and R 63-, 4-, 5- or 6-membered saturated heterocycles formed with the carbon atoms to which they are attached and containing 1, 2 or 3 heteroatoms selected from O and S as ring members are, for example, oxirane-2,2-diyl, thiirane-2,2-diyl, oxetane-2,2-diyl, oxetane-3,3-diyl, thietane-2,2-diyl, thietane-3,3-diyl, tetrahydrofuran-2,2-diyl, tetrahydrofuran-3,3-diyl, tetrahydrothiophene-2,2-diyl, tetrahydrothiophene-3,3-diyl, 1,3-dioxolane-2,2-diyl, 1,3-dioxolane-4,4-diyl, 1,3-dithiolane-2,2-diyl, 1,3-dithiolane-4,4-diyl, 1,3-oxathiolane-2,2-diyl, 1,3-oxathiolane-4,4-diyl, 1,3-oxathiolane-5,5-diyl, tetrahydropyran-2,2-diyl, tetrahydropyran-3,3-diyl, tetrahydropyran-4,4-diyl, tetrahydrothiopyran-2,2-diyl, tetrahydrothiopyran-3,3-diyl, tetrahydrothiopyran-4,4-diyl, 1,3-dioxane-2,2-diyl, 1,3-dioxane-4,4-diyl, 1,3-dioxane-5,5-diyl, 1,4-dioxane-2,2-diyl, oxepane-2,2-, -3,3- or -4,4-diyl, hexahydro-1,3-dioxepane-2,2-, -4,4- or -5,5-diyl, hexahydro-1,4-dioxepane-2,2-, -5,5- or -6,6-diyl, oxocane-2,2-, 3,3- or -4,4-diyl, thiacane-2,2-, 3,3- or -4,4-diyl, etc.

[0068] R 7 and R 8 Together with the carbon atoms to which they are attached, they can form a 3-, 4-, 5- or 6-membered saturated carbocycle or a 3-, 4-, 5- or 6-membered saturated heterocycle containing 1, 2 or 3 heteroatoms selected from O and S as ring members. This ring is spiro-bonded to the fused ring system to which R 7 and R 8 are attached, and the carbon atoms to which R 7 and R 8 are attached are spiro atoms. This ring is usually monocyclic.

[0069] Examples of saturated three- to six-membered monocyclic carbocycles formed by R 7 and R 8 together with the carbon atoms to which they are attached are cyclopropane-1,1-diyl, cyclobutane-1,1-diyl, cyclopentane-1,1-diyl and cyclohexane-1,1-diyl.

[0070] By R 7 and R 8Examples of saturated heterocycles containing 1, 2 or 3 heteroatoms selected from O and S as ring members, together with the carbon atoms to which they are attached, correspond to those given above for the rings formed by R 5 and R 6 together with the carbon atoms to which they are attached.

[0071] "Aryl" is a monocyclic, bicyclic or polycyclic carbocyclic (i.e., having no heteroatoms as ring members) aromatic group. An example of a monocyclic aromatic group is phenyl. In a bicyclic aryl ring, the two aromatic rings are fused, i.e., they share two adjacent C atoms as ring members. An example of a bicyclic aromatic group is naphthyl. In a polycyclic aryl ring, three or more rings are fused. Examples of polycyclic aryl groups are phenanthryl, anthracenyl, tetracenyl, 1H-benzo[a]phenalenyl, pyrenyl, etc. However, for the purposes of the present invention, "aryl" also encompasses bicyclic or polycyclic groups in which not all of the rings are aromatic, provided that at least one ring is aromatic; especially if the reaction site is on the aromatic ring (or on a functional group attached thereto). Examples are indanyl, indenyl, tetrahydronaphthyl, 6,7,8,9-tetrahydro-5H-benzo[7]annulenyl, fluorenyl, 9,10-dihydroanthracenyl, 9,10-dihydrophenanthryl, 1H-benzo[a]phenalenyl, etc., and ring systems in which not all of the rings are fused but are, for example, spiro-connected or bridged, such as benzonorbornenyl. In particular, the aryl group has 6 to 20, preferably 6 to 10 carbon atoms as ring members.

[0072] Examples of 5- or 6-membered heteroaromatic rings (or heteroaryl groups) containing 1, 2 or 3 heteroatoms selected from N, O and S as ring members are 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-1-yl, 1,2,4-triazol-2-yl, 1,2,4-triazol-3-yl, 1,3,4-triazol-1-yl, 1,3,4-triazol-2-yl, 1,2,5-oxadiazol-3-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,5-thiadiazol-3-yl, 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl and 2-pyrazinyl.

[0073] Salts of the compounds of formula I are preferably agriculturally acceptable salts. They can be formed by conventional methods, for example, by reacting the compound with an acid of the anion in question, or if compound I has an acidic center, by reacting it with a suitable base. The compounds I of the present invention have at least two basic centers, namely two basic nitrogen ring atoms, and thus the agriculturally acceptable salts are generally acid addition salts.

[0074] Suitable agriculturally acceptable salts are in particular those salts of cations or acid addition salts of those acids, the cations and anions of which have no adverse effect on the action of the compounds according to the invention. Suitable cations are in particular alkali metal (preferably lithium, sodium and potassium) ions, alkaline earth metal (preferably calcium, magnesium and barium) ions and transition metal (preferably manganese, copper, zinc and iron) ions, as well as ammonium (NH 4 + ) and substituted ammonium, where 1 to 4 hydrogen atoms are replaced by C 1 -C 4 -alkyl, C 1 -C 4 -hydroxyalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxy-C 1 -C4 -alkyl, hydroxy-C 1 -C 4 -alkoxy-C 1 -C 4 -substituted by alkyl, phenyl or benzyl. Examples of substituted ammonium ions include methylammonium, isopropylammonium, dimethylammonium, diisopropylammonium, trimethylammonium, tetramethylammonium, tetraethylammonium, tetrabutylammonium, 2-hydroxyethylammonium, 2-(2-hydroxyethoxy)ethylammonium, bis(2-hydroxyethyl)ammonium, benzyltrimethylammonium and benzyltriethylammonium. In addition, there are phosphonium ions, sulfonium ions, preferably tris(C 1 -C 4 -alkyl)sulfonium, and sulfoxide ions, preferably tris(C 1 -C 4 -alkyl)sulfoxide.

[0075] The anions of the available acid addition salts are mainly chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, hydrogen carbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and the anions of C 1 -C 4 -alkanoic acids, preferably formate, acetate, propionate and butyrate. They can be formed by reacting a compound of formula I with an acid of the corresponding anion, preferably hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid or nitric acid.

[0076] The term "stereoisomers" relates to enantiomers and diastereoisomers, including Z / E isomers.

[0077] Depending on the substitution pattern, a compound of formula (I) may have one or more stereogenic centers. By way of example only, the stereogenic centers in compound (I) are the C atoms bearing R 5 and R 6 , provided of course that R 5 and R 6 have different meanings, or provided that the ring formed by R 5 and R 6 together with said carbon atom does not have a rotational mirror axis. Additionally, the C atoms bearing R 7 and R 8 (if present, i.e., if m≠0) are stereogenic centers, provided of course that R 7 and R 8 have different meanings, or provided that the ring formed by R 7 and R 8 together with said carbon atom does not have a rotational mirror axis. The present invention provides for the use of pure enantiomers, pure diastereoisomers, and mixtures of enantiomers and / or diastereoisomers.

[0078] For the purposes of the present invention, the term "pure enantiomer" is understood to mean a non-racemic mixture of a specific compound in which the desired enantiomer is present in an enantiomeric excess of > 90% ee. For the purposes of the present invention, the term "pure diastereomer" is understood to mean a mixture of diastereomers of a specific compound in which the desired diastereomer is present in an amount of > 90% based on the total amount of the diastereomers of said compound.

[0079] The term N-oxide relates to a form of compound I in which at least one nitrogen atom is present in oxidized form (as NO). More precisely, it relates to any compound I having at least one tertiary nitrogen atom oxidized to an N-oxide moiety. The N-oxides of compound I can in particular be prepared by oxidizing the ring nitrogen atoms of, for example, a pyridine ring and / or any nitrogen-containing heterocyclic or heteroaromatic group present, with a suitable oxidizing agent such as a peroxycarboxylic acid or other peroxide, for example the nitrogen atom adjacent to CR 5 R 6 in the ortho position. A person skilled in the art knows whether and at which positions compound I can form N-oxides.

[0080] Compound (I) can exist in different tautomeric forms. For example, if the ring bearing R 5 and R 6 is a lactam, i.e. if the ring contains an amide group as a ring member ( = an unsubstituted secondary nitrogen ring atom adjacent to a carbon ring atom bearing an oxo group), then this ring moiety -N(H)-C(=O)- can be in equilibrium with its tautomeric form -N=C(OH)-. This is the case, for example, if m is 0, R 5 and R 6 together form an oxo group, Y is NR 9 and R 9 is hydrogen.

[0081] Biochemical definition

[0082] The term "dihydroorotate dehydrogenase" (abbreviated as DHODH) refers to class 2 enzymes of DHODH (mitochondrial origin, FMN as cofactor) EC 1.3.5.2, which oxidize dihydroorotate to orotate while reducing a quinone acting as an oxidizing agent to a quinonol.

[0083] In the context of the present invention, the term "resistance to dihydroorotate dehydrogenase inhibitors" of a phytopathogenic fungus refers to resistance to one or more prior art quinoline-type phytopathogen inhibitors as described in EP-A-2522658, EP-A-1736471 or WO 2017 / 153380, in particular resistance to at least one compound having the formula (1), (2) or (3):

[0084]

[0085] In particular, the resistance is conferred by at least one mutation in the DHODH structural gene, resulting in at least one amino acid residue change, such as the addition, inversion, deviation or substitution, especially deletion or substitution, more especially substitution, of at least one amino acid residue of the endogenous non-mutated DHODH enzyme. Such a mutation can, for example, induce a change in the primary, secondary, tertiary or quaternary protein structure of the enzyme, which affects the docking of the inhibitory molecule to the enzyme, for example into the substrate pocket of the enzyme.

[0086] The term "method for combating phytopathogenic fungi resistant due to a mutation conferring resistance in the DHODH gene" includes applying a compound of formula I according to the invention to such resistant phytopathogenic fungi. It has been observed that populations of phytopathogenic fungi consisting apparently of non-resistant strains under field conditions can readily develop resistance. The compounds according to the invention can also be applied under such conditions in order to prevent the formation of resistance and the spread of resistant strains. In this regard, it is useful that they also have strong activity against non-resistant phytopathogenic fungi.

[0087] The term "phytopathogenic fungi resistant due to a mutation conferring resistance in the DHODH gene" is to be understood as meaning that at least 10%, more preferably at least 30%, even more preferably at least 50%, and most preferably at least 75%, especially between 90% and 100%, of the fungal isolates to be controlled contain a mutation in the endogenous DHODH gene conferring resistance to the prior art inhibitors as defined above.

[0088] The term "resistance-inducing mutation" or "resistance-conferring mutation" describes the effect of a mutation introduced into the coding sequence of a specific enzyme (in the present invention DHODH, as expressed in phytopathogenic fungi) on the ability of a specific inhibitor substance or class of inhibitor substances to combat said phytopathogen. By such a mutation, the inhibitory activity of such a substance can be partially reduced or completely eliminated. For example, the inhibitor concentration of such a substance that causes a 50% reduction in growth (e.g. expressed as IC 50 concentration, as determined in the following experimental section) can be increased relative to the corresponding value observed for the non-mutated wild-type strain of the phytopathogen under otherwise identical conditions. For example, the resistance can be increased by at least 2-fold (i.e., the corresponding IC 50 concentration is at least doubled), for example by a factor in the range from 2 to 1 exp 6, or especially from 5 to 10,000, more especially from 10 to 5,000 or 50 to 1,000, or in particular from 100 to 500.

[0089] The term "corresponding amino acid sequence position" refers to amino acid residues in different species of a particular type of protein, in particular amino acid residues of DHODH enzymes isolated from different phytopathogenic fungi, which are located within the corresponding amino acid sequence, in particular within a sequence motif or consensus sequence or signature, and which are predicted to have a similar effect on the functional characteristics of the protein, such as enzyme activity or substrate binding ability or inhibitor binding ability. Such corresponding amino acid sequence positions can be readily derived from so-called amino acid sequence alignments. An example thereof is depicted in Figure 1 of the present application. Generating a suitable sequence alignment is well within the capabilities of a person skilled in the art.

[0090] The term "motif" or "consensus sequence" or "signature" refers to a short conserved region in optionally evolutionarily related protein sequences. A motif is typically a highly conserved part of a domain, but can also include only a part of a domain.

[0091] A "protein family" is defined as a group of proteins sharing a common evolutionary origin, as reflected by their related functions, sequence similarity or similar primary, secondary or tertiary structures. Proteins within a protein family are typically homologous and have a similar structure with conserved functional domains and motifs.

[0092] As used herein, the term "host cell" or "transformed cell" refers to a cell (or organism) that has been altered to contain at least one nucleic acid molecule, such as a recombinant gene encoding a desired protein or nucleic acid sequence, which upon transcription produces at least one functional polypeptide of the present invention, in particular a DHODH enzyme or a mutant thereof as defined herein. Host cells are in particular bacterial cells, fungal cells or plant cells. A host cell can contain, for example, a recombinant gene or several genes organized as an operon, which have been integrated into the nuclear or organelle genome of the host cell. Alternatively, the host can contain the recombinant gene extrachromosomally.

[0093] The term "organism" refers to any non-human multicellular or unicellular organism, such as a plant or a microorganism. In particular, a microorganism is a bacterium, yeast, alga or fungus.

[0094] The term "plant" includes plant cells, including plant protoplasts, plant tissues, plant cell tissue cultures, or parts of a plant, or plant organs, such as roots, stems, leaves, flowers, pollen, ovules, embryos, fruits, etc., which give rise to regenerated plants.

[0095] "Proteinogenic" amino acids particularly include (single letter code): G, A, V, L, I, F, P, M, W, S, T, C, Y, N, Q, D, E, K, R and H.

[0096] Examples

[0097] Unless otherwise indicated, the following description of the general and preferred embodiments of the present invention relates to the uses and methods of the present invention and to compositions. The following preferred embodiments of the variables of the compounds of formula I, in particular with respect to their substituents R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, Y, m and n and any subgroup thereof, the comments made in accordance with the characteristics of the uses and methods of the present invention and of the compositions of the present invention are valid in isolation and in particular in every possible combination with one another.

[0098] a) Compound (I)

[0099] In a preferred embodiment, R 1 is hydrogen.

[0100] In a preferred embodiment, R 4 is hydrogen.

[0101] In a preferred embodiment, R 1 and R 4 are both hydrogen.

[0102] In a preferred embodiment, R 2 is halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyloxy or C 2 -C 6 -alkynyloxy. More preferably, R 2 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl, and in particular is C 1 -C4 -alkyl

[0103] In a preferred embodiment, R 3 is halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenoxy or C 2 -C 6 -alkynoxy. More preferably, R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl.

[0104] In a preferred embodiment, R 2 and R 3 are each independently C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl. More preferably, R 2 is C 1 -C 4 -alkyl, and R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl.

[0105] In particular, R 1 and R 4 are hydrogen, and R 2 and R 3 are each independently C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl. More particularly, R 1 and R 4 are hydrogen, R 2 is C1 -C 4 -alkyl, and R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl.

[0106] In a preferred embodiment,

[0107] R 5 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, phenyl or benzyl, wherein the last-mentioned 4 aliphatic or aromatic groups are unsubstituted or carry 1 or 2 substituents R 5a ; wherein

[0108] each R 5a is independently halogen or C 1 -C 6 alkoxy;

[0109] R 6 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, phenyl or benzyl, wherein the last-mentioned 4 aliphatic or aromatic groups are unsubstituted or carry 1 or 2 substituents R 6a ; wherein

[0110] each R 6a is independently halogen or C 1 -C 6 alkoxy;

[0111] Or

[0112] R 5 and R 6 together form an oxo group (=O);

[0113] Or

[0114] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbocyclic or heterocyclic ring is unsubstituted or carries 1, 2 or 3 substituents R 56 ; wherein each R 56 is independently C 1 -C 4 -alkyl.

[0115] Even more preferably,

[0116] R 5 and R 6 are, independently of each other, hydrogen, C 1 -C 6 -alkyl or phenyl;

[0117] or

[0118] R 5 and R 6 together form an oxo group (=O);

[0119] or

[0120] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbon ring or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 ; wherein each R 56 is independently C 1 -C 4 -alkyl.

[0121] In particular,

[0122] R 5 and R 6 are, independently of each other, hydrogen, C 1 -C 6 -alkyl or phenyl, where in the case where m is 0, at least one of R 5 and R 6 is not hydrogen;

[0123] or

[0124] R 5 and R 6 together form an oxo group (=O);

[0125] or

[0126] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbon ring or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 ; wherein each R 56 is independently C 1 -C 4 -alkyl.

[0127] In a preferred embodiment,

[0128] R 7 and R 8 are each independently hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0129] or

[0130] R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring.

[0131] In a preferred embodiment, each X is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; and more preferably halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy.

[0132] n is preferably 0, 1 or 2.

[0133] In one embodiment, Y is O and m is 0.

[0134] In another embodiment, Y is NR 9 and m is 0.

[0135] In yet another embodiment, Y is O and m is 1.

[0136] In a preferred embodiment, R 9 is hydrogen, -CH(=O), -C(=O)C 1 -C 6 -alkyl, -C(=O)C 2 -C 6 -alkenyl, -C(=O)C 2 -C 6 -alkynyl, -C(=O)C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 4 -haloalkyl, C 3-C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, -S(=O) 2 -R 9a , wherein R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents; a five- or six-membered heteroaryl or phenyl; wherein the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O and S as ring members; wherein the phenyl is unsubstituted or bears 1, 2, 3, 4 or 5 substituents selected from the group consisting of: CN, halogen, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy.

[0137] More preferably, R 9 is hydrogen, C 1 -C 4 -alkyl, -C(=O)C 1 -C 3 -alkyl or -S(=O) 2 -R 9a , wherein R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents.

[0138] In particular, in compound (I),

[0139] R 1 is hydrogen;

[0140] R2 is C 1 -C 4 -alkyl;

[0141] R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

[0142] R 4 is hydrogen;

[0143] R 5 is hydrogen, C 1 -C 6 -alkyl or phenyl;

[0144] R 6 is hydrogen, C 1 -C 6 -alkyl or phenyl;

[0145] or

[0146] R 5 and R 6 together form an oxo group (=O);

[0147] or

[0148] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbocyclic or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 ; wherein

[0149] each R 56 is independently C 1 -C 4 -alkyl;

[0150] R 7 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0151] R 8 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0152] or

[0153] R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring;

[0154] Each X is independently a halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy;

[0155] R 9 is hydrogen, C 1 -C 4 -alkyl, -C(=O)C 1 -C 3 -alkyl or -S(=O) 2 -R 9a ;

[0156] wherein

[0157] R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents; and

[0158] n is 0, 1 or 2.

[0159] More preferably,

[0160] R 1 is hydrogen;

[0161] R 2 is C 1 -C 4 -alkyl;

[0162] R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

[0163] R 4 is hydrogen;

[0164] R 5 is hydrogen, C 1 -C 6 -alkyl or phenyl;

[0165] R6 is hydrogen, C 1 -C 6 -alkyl or phenyl;

[0166] wherein when m is 0, at least one of R 5 and R 6 is not hydrogen;

[0167] or

[0168] R 5 and R 6 together form an oxo group (=O);

[0169] or

[0170] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbon ring or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 ; wherein

[0171] each R 56 is independently C 1 -C 4 -alkyl;

[0172] R 7 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0173] R 8 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0174] or

[0175] R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring;

[0176] each X is independently halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy;

[0177] R 9 is hydrogen, C 1 -C 4 -alkyl, -C(=O)C 1 -C 3 -alkyl or -S(=O) 2 -R 9a ;

[0178] wherein

[0179] R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents; and

[0180] n is 0, 1 or 2.

[0181] In one embodiment, Y is O and m is 0. This gives rise to a compound having the formula (I.A)

[0182]

[0183] wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and n have one of the above general meanings or particularly one of the above preferred meanings.

[0184] Particularly, in the compound (I.A),

[0185] R 1 is hydrogen;

[0186] R 2 is C 1 -C 4 -alkyl;

[0187] R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

[0188] R 4 is hydrogen;

[0189] R 5 is hydrogen, C 1 -C 6 -alkyl or phenyl;

[0190] R 6 is C 1 -C 6 -alkyl or phenyl;

[0191] or

[0192] R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbocyclic or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 ; wherein

[0193] each R 56 is independently C 1 -C 4 -alkyl;

[0194] each X is independently halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy; and

[0195] n is 0, 1 or 2.

[0196] In another embodiment, Y is NR 9 and m is 0. This gives rise to a compound having the formula (I.B)

[0197]

[0198] wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , X and n have one of the above general meanings or in particular one of the above preferred meanings.

[0199] In particular, in the compound (I.B),

[0200] R 1 is hydrogen;

[0201] R 2 is C 1 -C 4 -alkyl;

[0202] R 3 is C 1 -C 4 -alkyl or C 1 -C4 - haloalkyl;

[0203] R 4 is hydrogen;

[0204] R 5 is C 1 - C 6 - alkyl;

[0205] R 6 is C 1 - C 6 - alkyl;

[0206] Each X is independently a halogen;

[0207] R 9 is hydrogen, C 1 - C 4 - alkyl, - C(=O)C 1 - C 3 - alkyl or - S(=O) 2 - R 9a ;

[0208] wherein

[0209] R 9a is phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 - C 4 - alkyl substituents; and

[0210] n is 0, 1 or 2.

[0211] In another embodiment, Y is O and m is 1. This gives rise to a compound having the formula (I.C)

[0212]

[0213] wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and n have one of the above general meanings or particularly one of the above preferred meanings.

[0214] Particularly, in the compound (I.C),

[0215] R 1 is hydrogen;

[0216] R 2 is C 1 - C 4 - alkyl;

[0217] R 3is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

[0218] R 4 is hydrogen;

[0219] R 5 is hydrogen or C 1 -C 6 -alkyl;

[0220] R 6 is hydrogen or C 1 -C 6 -alkyl;

[0221] or

[0222] R 5 and R 6 together form an oxo group (=O);

[0223] R 7 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0224] R 8 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;

[0225] or

[0226] R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring; and

[0227] n is 0.

[0228] Examples of preferred compounds are the compounds having the formulas I.A.1 to I.A.6, I.B.1 to I.B.4 and I.C.1 to I.C.4, where X, n, R 5 and R 6 , R 7 , R 8 and R 9Has one of the general or preferred meanings given above. Examples of preferred compounds are the individual compounds compiled in the following table. In addition, the meanings mentioned below for the individual variables in the table are themselves particularly preferred embodiments of the substituents under discussion, independent of the combinations in which they are mentioned.

[0229]

[0230]

[0231] Particularly preferred compounds I.A.1, I.A.2, I.A.3, I.A.4, I.A.5 and I.A.6 are listed in Tables 1 to 7 below.

[0232] Table 1

[0233] Compounds having the formula I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, where n is 0, and the R of the compound 5 and R 6 combinations each correspond to a row of Table A

[0234] Table 2

[0235] Compounds having the formula I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, where n is 1, X is 8-F, and the R of the compound 5 and R 6 combinations each correspond to a row of Table A

[0236] Table 3

[0237] Compounds having the formula I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, where n is 1, X is 8-Cl, and the R of the compound 5 and R 6 combinations each correspond to a row of Table A

[0238] Table 4

[0239] Compounds having the formula I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, where n is 1, X is 7-methoxy, and the R of the compound 5 and R 6 combinations each correspond to a row of Table A

[0240] Table 5

[0241] Compounds having the formula I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, where n is 2, X is 7,8-F2 and the combination of R 5 and R 6 of the compound corresponds to a row of Table A in each case

[0242] Table 6

[0243] Compounds having the formulae I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, wherein n is 2 and X is 6,8-F 2 and the combination of R 5 and R 6 of the compound corresponds to a row of Table A in each case

[0244] Table 7

[0245] Compounds having the formulae I.A.1, I.A.2, I.A.3, I.A.4, I.A.5, I.A.6, wherein n is 2 and X is 5,8-F 2 and the combination of R 5 and R 6 of the compound corresponds to a row of Table A in each case

[0246] Particularly preferred compounds I.B.1, I.B.2, I.B.3 and I.B.4 are listed in Tables 8 to 14 below.

[0247] Table 8

[0248] Compounds having the formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 0, and the combination of R 5 , R 6 and R 9 of the compound corresponds to a row of Table B in each case

[0249] Table 9

[0250] Compounds having the formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 1, X is 8-F, and the combination of R 5 , R 6 and R 9 of the compound corresponds to a row of Table B in each case

[0251] Table 10

[0252] Compounds having the formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 1, X is 8-Cl, and the combination of R 5 , R 6 and R 9 of the compound corresponds to a row of Table B in each case

[0253] Table 11

[0254] Compounds of formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 1, X is 8-methyl, and the R 5 , R 6 and R 9 combinations in each case correspond to a row of Table B

[0255] Table 12

[0256] Compounds of formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 1, X is 8-methoxy, and the R 5 , R 6 and R 9 combinations in each case correspond to a row of Table B

[0257] Table 13

[0258] Compounds of formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 2, X is 7,8-F 2 , and the R 5 , R 6 and R 9 combinations in each case correspond to a row of Table B

[0259] Table 14

[0260] Compounds of formulae I.B.1, I.B.2, I.B.3, I.B.4, wherein n is 2, X is 7-F,8-methoxy, and the R 5 , R 6 and R 9 combinations in each case correspond to a row of Table B

[0261] Particularly preferred compounds I.C.1, I.C.2, I.C.3 and I.C.4 are listed in Tables 15 to 21 below.

[0262] Table 15

[0263] Compounds of formulae I.C.1, I.C.2, I.C.3, I.C.4, wherein n is 0, and the R 5 , R 6 , R 7 and R 8 combinations in each case correspond to a row of Table C

[0264] Table 16

[0265] Compounds of formulae I.C.1, I.C.2, I.C.3, I.C.4, wherein n is 1, X is 8-F, and the R5 , R 6 , R 7 and R 8 's combination corresponds to a row in Table C in each case

[0266] Table 17

[0267] Compounds with formulae I.C.1, I.C.2, I.C.3, I.C.4, where n is 1, X is 8-Cl, and the R of the compound 5 , R 6 , R 7 and R 8 's combination corresponds to a row in Table C in each case

[0268] Table 18

[0269] Compounds with formulae I.C.1, I.C.2, I.C.3, I.C.4, where n is 1, X is 7-methoxy, and the R of the compound 5 , R 6 , R 7 and R 8 's combination corresponds to a row in Table C in each case

[0270] Table 19

[0271] Compounds with formulae I.C.1, I.C.2, I.C.3, I.C.4, where n is 2, X is 7,8-F 2 , and the R of the compound 5 , R 6 , R 7 and R 8 's combination corresponds to a row in Table C in each case

[0272] Table 20

[0273] Compounds with formulae I.C.1, I.C.2, I.C.3, I.C.4, where n is 2, X is 6,8-F 2 , and the R of the compound 5 , R 6 , R 7 and R 8 's combination corresponds to a row in Table C in each case

[0274] Table 21

[0275] Compounds with formulae I.C.1, I.C.2, I.C.3, I.C.4, where n is 2, X is 5,8-F 2 , and the R of the compound 5 , R 6 , R 7 and R8 The combination corresponds to a row of Table C in each case

[0276] Table A

[0277]

[0278]

[0279]

[0280] Me = methyl; Et = ethyl, n-Pr = n-propyl, iPr = isopropyl, n-Bu = n-butyl [(CH 2 ) 3 CH 3 , 2-Bu = 2-butyl (sec-butyl; CH(CH 3 )CH 2 CH 3 ), iBu = isobutyl (CH 2 CH(CH 3 ) 2 ), t-Bu = tert-butyl (C(CH 3 ) 3 ), iPt = CH 2 -C(CH 3 ) 3 ), iHx = CH 2 CH 2 C(CH 3 ) 3 ), iHpt = CH 2 -CH(CH 3 )-C(CH 3 ) 3 ), iDc = CH 2 -CH(C(CH 3 ) 3 ) 2 ), OMe = methoxy, Ph = phenyl, Bz = benzyl, 2-F-Bz = CH 2 -2F-Ph, 4-F-Bz = CH 2 -4F-Ph

[0281] Table B

[0282]

[0283] Table C

[0284]

[0285] R.1 to R.18 represent those composed of R 5 and R 6The following rings formed together with the carbon atoms to which they are attached:

[0286]

[0287]

[0288] The arrow indicates the attachment points of the carbon ring atom bearing R 5 and R 6 to its two other adjacent atoms (i.e., attached to N, and in the case of I.A.1 to I.A.6 attached to O, and in the case of I.B.1 to I.B.4 attached to NR 9 , and in the case of I.C.1 to I.C.4, attached to the carbon ring atom bearing R 7 and R 8 ).

[0289] Alternatively stated,

[0290] in the case of R.1, R 5 and R 6 together form a bridging group -CH 2 CH 2 -,

[0291] in the case of R.2, R 5 and R 6 together form a bridging group -CH 2 CH 2 CH 2 -,

[0292] in the case of R.3, R 5 and R 6 together form a bridging group -CH(CH 3 )CH 2 CH 2 -,

[0293] in the case of R.4, R 5 and R 6 together form a bridging group -C(CH 3 ) 2 CH 2 CH 2 -,

[0294] in the case of R.5, R 5 and R 6 together form a bridging group -CH 2 C(CH 3 ) 2 CH 2 -,

[0295] in the case of R.6, R5 and R 6 together form a bridging group -CH 2 CH 2 CH 2 CH 2 -

[0296] In the case of R.7, R 5 and R 6 together form a bridging group -CH 2 CH 2 CH 2 CH 2 CH 2 -

[0297] In the case of R.8, R 5 and R 6 together form a bridging group -OCH 2 -

[0298] In the case of R.9, R 5 and R 6 together form a bridging group -OCH(CH 3 )-

[0299] In the case of R.10, R 5 and R 6 together form a bridging group -OCH 2 CH 2 -

[0300] In the case of R.11, R 5 and R 6 together form a bridging group -CH 2 OCH 2 -

[0301] In the case of R.12, R 5 and R 6 together form a bridging group -OCH 2 CH 2 CH 2 -

[0302] In the case of R.13, R 5 and R 6 together form a bridging group -CH 2 OCH 2 CH 2 -

[0303] In the case of R.14, R 5 and R 6 together form a bridging group -CH 2 OCH(CH 3)CH 2 -,

[0304] In the case of R.15, R 5 and R 6 together form a bridging group -CH 2 OCH 2 C(CH 3 ) 2 -,

[0305] In the case of R.16, R 5 and R 6 together form a bridging group -OCH 2 CH 2 CH 2 CH 2 -,

[0306] In the case of R.17, R 5 and R 6 together form a bridging group -CH 2 OCH 2 CH 2 CH 2 -,

[0307] In the case of R.18, R 5 and R 6 together form a bridging group -CH 2 CH 2 OCH 2 CH 2 -.

[0308] Furthermore, compounds used in the examples, their stereoisomers, tautomers, N-oxides, and agriculturally acceptable salts are particularly preferred.

[0309] Compound I is mainly known, for example, from PCT / EP2022 / 062598, PCT / EP2022 / 062622, and PCT / EP2022 / 070790.

[0310] As long as the compounds identified above are new, the present invention also relates to these compounds themselves, and to their N-oxides, tautomers, stereoisomers, or agriculturally acceptable salts.

[0311] Compound I can be prepared as shown in the following scheme, where, unless otherwise stated, the definition of each variable is as defined above for the compound of formula I. Compounds of formula I can be prepared according to methods described in the prior art or similar to these methods. The synthesis utilizes starting materials that are commercially available or can be prepared according to conventional procedures starting from readily available compounds.

[0312] For example, compound I (hereinafter referred to as I', where Y is O) can be prepared by a palladium-catalyzed Suzuki coupling reaction between boronic acid derivative 2 and compound 1 (Z = halide or trifluoromethanesulfonate) using a palladium complex in an organic solvent. Preferably, the reaction is carried out at an elevated temperature, preferably between 60 °C and 160 °C, and 1 to 3 equivalents of boronic acid derivative 2 are used per 1 equivalent of compound 1, as described in WO 2009 / 119089.

[0313]

[0314] The compound of formula 1 (where Z is a trifluoromethanesulfonate group) can be prepared from cyclic amide compound 3 by treatment with trifluoromethanesulfonic anhydride in a halogenated aliphatic hydrocarbon solvent (such as chloroform, dichloromethane or dichloroethane) in the presence of a base (such as pyridine, 2,6-dimethylpyridine, 2,3,5-trimethylpyridine, triethylamine, tributylamine, diisopropylethylamine, tert-bicyclic amine or amidine (such as 1,4-diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene or 1,8-diazabicyclo[5.4.0]undec-7-ene) or aromatic amine (such as N,N-dimethylaniline, N,N-diethylaniline or 4-dimethylaminopyridine)), as described in WO 2009 / 119089 and EP 2179994B1. The compound of formula 1 (where Z is a halide) can be prepared from cyclic amide compound 3 by treatment with a suitable halogenating agent (such as triphenylphosphine and carbon tetrachloride, triphenylphosphine dichloride, phosgene, oxalyl chloride or thionyl chloride), as described in US 2011 / 0136782.

[0315]

[0316] The cyclic amide compound having the formula 3 (hereinafter referred to as compound 3', where m is 0) is commercially available or can be prepared from the corresponding salicylamide 4 by forming an acetal with a dimethoxyalkane or dimethoxycycloalkane in an organic solvent and in the presence of an acid such as p-toluenesulfonic acid (p-TsOH), pyridinium p-toluenesulfonate, sulfuric acid or acetic acid (as described, for example, in Tetrahedron (2015), 71(34), 5554-5561, Journal of Organic Chemistry (1981), 46(16), 3340-2, or Bioorganic & Medicinal Chemistry (2006), 14(6), 1978-1992). The compound having the formula 3' can also be prepared via the condensation between salicylamide 4 and ketone 6, which is catalyzed by a secondary amine such as pyrrolidine, morpholine, etc. The reaction is preferably carried out in refluxing benzene or toluene with 10% amine catalyst (see, for example, J. Org. Chem. 1981, 46, 3340-3342 or Synthesis 1978, 886).

[0317]

[0318] The cyclic amide compound having the formula 3 (hereinafter referred to as compound 3", where m is 1) can be prepared by reacting the cycloacetophenone derivative 7 to form an oxime 8 and then subjecting it to a Beckmann rearrangement to 3", or alternatively by directly converting the cycloacetophenone derivative 7 in one step by the Schmidt reaction to produce 3". Various variations of these two reactions have been reported. The Schmidt reaction can be carried out, for example, by reacting the ketone 7 in sodium azide in the presence of a strong acid such as concentrated hydrochloric acid, sulfuric acid, trifluoroacetic acid or methanesulfonic acid, in the absence of a solvent or in a solvent such as acetonitrile, chloroform or dichloromethane. In the Beckmann rearrangement, the oxime 8 is reacted with polyphosphoric acid or its trimethylsilyl ester, or with a Lewis acid such as aluminum triiodide or iron(III)-impregnated montmorillonite or with thionyl chloride in the absence of a solvent or in the presence of a solvent such as acetonitrile. Alternatively, 3" can be prepared by forming the methanesulfonate or toluenesulfonate of the oxime 8 and then treating it with a base such as aqueous sodium hydroxide or with a Lewis acid such as diethylaluminum chloride, as described in Heterocycles 1994, 38(2), 305-18 or US2011 / 0136782 A1.

[0319]

[0320] Alternatively, compound 3” can be prepared in a one-pot reaction by copper(II)-catalyzed Beckmann rearrangement of ketone 7 using hydroxylamine-O-sulfonic acid as the aminating agent under mild reaction conditions, as described in Synthesis 2019, 51(19), 3709-3714.

[0321] The cyclic acetophenone derivative 7 is commercially available or can be prepared starting from 2-hydroxyacetophenone via a classical ring-closing reaction using the corresponding ketone in the presence of pyrrolidine, as described in Bioorganic & Medicinal Chemistry (2008), 16(11), 6124-6130 or in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1995).

[0322] Compound I (hereinafter referred to as I”, where m is 0 and Y is NR 9 ) can be prepared from compound 10 by alkylation or acylation in the presence of a base such as an alcoholate or hydride of potassium or sodium. Dialkyl sulfates can also be used to effect the alkylation or acylation, as described in US 3,625,959. Compound 10 can be prepared by reacting a ketoneamine compound 9 with a ketone or aldehyde having formula 6 in the presence of ammonium acetate. In some cases, the presence of an acid like p-toluenesulfonic acid (p-TsOH), pyridinium p-toluenesulfonate, sulfuric acid or acetic acid improves the yield (see, for example, Chemistry Select (2018), 3(32), 9388-9392 and Organic & Biomolecular Chemistry (2003), 1(2), 367-372).

[0323]

[0324] Compound 9 is commercially available or can be obtained by oxidizing amino alcohol 14 using, for example, manganese dioxide according to the general procedure outlined in the following scheme, as described in Inorganica Chimica Acta (2012), 382, 72 - 78, WO 2000 / 038618, CN 107879989A, or Chinese Science Bulletin 2010, 55(25), 2817 - 2819. Compound 14 can be prepared by catalytic hydrogenation of the corresponding nitro alcohol 13 using Raney nickel, as described in WO 2000 / 038618 or Inorganica Chimica Acta 2012, 382, 72 - 78. Nitro alcohol 13 can be prepared from 11 by phenylmagnesium bromide-mediated ortho-iodine-magnesium exchange followed by addition of commercially available aldehyde 12 as described by Knochel and co-workers (Angew. Chem., Int. Ed., 2002, 41, 1610). 2 The ortho iodine-magnesium exchange and subsequent addition of commercially available aldehyde 12 are used for preparation.

[0325]

[0326] Compounds having the formula I” (wherein R 9 is an alkoxy group) can be prepared from 13 via the following synthetic route, which is characterized by the selective catalytic hydrogenation of nitro alcohol 13 to the corresponding N-arylhydroxylamine 15 using passivated Raney nickel treated with a combined solution of ammonia and DMSO as described in RSC Advances 2020, 28585 - 28594 or platinum on carbon (type F 103RS / W, from Degussa) as described in IN1996CH00112.

[0327]

[0328] Compound 16 can be prepared by oxidizing 15 using, for example, manganese dioxide as described in Inorganica Chimica Acta 2012, 382, 72 - 78 and WO 2000 / 038618. Protected hydroxylamine 17 can be prepared by methods well-known in the literature for amino protecting groups as discussed in Theodora W. Greene's book "Protective Groups in Organic Synthesis". The boc protecting group shown above is obtained, for example, by reaction with di-tert-butyl dicarbonate in a suitable solvent such as DMSO. Compound 17 can be alkylated using a standard base such as LDA, NaH or NaHMDS to deprotonate the hydroxylamine, and then an alkylating agent having a suitable leaving group such as a halide, mesylate or triflate is added in a suitable solvent to provide compound 18 (see, for example, CN 207973751). The boc protecting group can be removed by any method known in the literature, such as TFA in dichloromethane, to give compound 19 (see, for example, WO 2000 / 038618). Finally, compound I can be prepared from 19 by treatment with NH 4 OAc (where R 9 is an alkoxy group) as described in Chemistry Select 2018, 3(32), 9388 - 9392 or Organic & Biomolecular Chemistry 2003, 1(2), 367 - 372.

[0329] The N-oxide of compound I can be prepared according to conventional oxidation methods, for example, by treatment of compound I with an organic peracid such as m-chloroperoxybenzoic acid (see WO 03 / 64572 or J. Med. Chem. 38(11), 1892 - 903, 1995); or with an inorganic oxidant such as hydrogen peroxide (see J. Heterocyc. Chem. 18(7), 1305 - 8, 1981) or potassium peroxymonosulfate preparation (see J. Am. Chem. Soc. 123(25), 5962 - 5973, 2001). The oxidation can produce the pure mono-N-oxide or a mixture of different N-oxides, which can be separated by conventional methods such as chromatography.

[0330] Generally, compounds of formula I (including their stereoisomers, salts and N-oxides and their precursors) can be prepared by the methods described above during the synthesis process. If a single compound cannot be prepared via the routes described above, they can be prepared by the derivation of other compounds I or corresponding precursors or by conventional modification of the synthesis route. For example, in a single case, certain compounds of formula (I) can advantageously be prepared from other compounds of formula (I) by derivatization (e.g., by ester hydrolysis, amidation, esterification, ether cleavage, olefination, reduction, oxidation, etc.) or by conventional modification of the synthesis route.

[0331] The reaction mixture is worked up in a conventional manner, for example by mixing with water, separating the phases, and (if appropriate) purifying the crude product by chromatography (e.g., on alumina or on silica gel). Some of the intermediates and final products can be obtained in the form of a colorless or light brown viscous oil, from which the volatile components are removed or purified under reduced pressure and at a moderate elevated temperature. If the intermediates and final products are obtained in solid form, they can be purified by recrystallization or trituration.

[0332] Compound I and its compositions can be used as foliar fungicides, seed dressing fungicides and soil fungicides in crop protection.

[0333] Compound I and its compositions are preferably used for controlling phytopathogenic fungi as defined above or below on various cultivated plants, such as cereals, e.g., wheat, rye, barley, triticale, oats or rice; sugar beet, e.g., sugar beet or fodder beet; fruits, e.g., pomes (apples, pears, etc.), stone fruits (e.g., plums, peaches, almonds, cherries) or soft fruits, also known as berries (strawberries, raspberries, blackberries, currants, etc.); leguminous plants, e.g., lentils, peas, alfalfa or soybeans; oil plants, e.g., rape, mustard, olive, sunflower, coconut, cocoa bean, castor oil plant, oil palm, groundnut or soybean; cucurbits, e.g., pumpkin, cucumber or melon; fiber plants, e.g., cotton, flax, hemp, or jute; citrus fruits, e.g., oranges, lemons, grapefruits or tangerines; vegetables, e.g., spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, gourds or red peppers; laurel family plants, e.g., avocado, cinnamon or camphor; energy and raw material plants, e.g., corn, soybean, rape, sugar cane or oil palm; corn; tobacco; nuts; coffee; tea; bananas; grapevines (table grapes and grape juice grapevines); hops; turf; stevia (also known as stevia rebaudiana); natural rubber plants; or ornamental and forest plants, e.g., flowers, shrubs, broad-leaved trees or evergreens (conifers, eucalyptus, etc.); plant propagation materials such as seeds; and crop materials of these plants.

[0334] More preferably, compound I and its compositions are used, respectively, for controlling fungi as defined above or below on the following: field crops such as potato, sugar beet, tobacco, wheat, rye, barley, oats, rice, maize, cotton, soybean, oilseed rape, legumes, sunflower, coffee or sugar cane; fruits; vines; ornamental plants; or vegetables such as cucumber, tomato, kidney bean or pumpkin.

[0335] The term "plant propagation material" shall be understood to denote all generative parts of plants, such as seeds; and vegetative plant material which can be used for plant propagation, such as cuttings and tubers (e.g. potatoes). This includes seeds, roots, fruits, tubers, bulbs, rhizomes, shoots, buds and other parts of plants; including seedlings and young plants which are transplanted after germination or emergence from the soil.

[0336] Preferably, plant propagation materials are treated, respectively, with compound I and its compositions for controlling fungi as defined above or below on the following: cereals such as wheat, rye, barley and oats; rice, maize, cotton and soybean.

[0337] The term "cultivated plant" shall be understood to include plants which have been modified by mutagenesis or genetic engineering in order to endow the plant with new traits or to modify existing traits. Mutagenesis includes random mutagenesis using X-rays or mutagenic chemicals, and includes targeted mutagenesis to generate mutations at specific loci in the plant genome. Targeted mutagenesis often uses oligonucleotides or proteins such as CRISPR / Cas, zinc finger nucleases, TALEN or meganucleases. Genetic engineering typically uses recombinant DNA techniques to generate modifications in the plant genome which cannot readily be obtained by crossing, mutagenesis or natural recombination in the natural environment. Typically, one or more genes are integrated into the genome of the plant in order to add traits or to improve or modify traits. These integrated genes are also referred to as transgenes, and plants containing such transgenes are referred to as transgenic plants. The plant transformation process typically results in a number of transformation events which differ in the genomic loci at which the transgene has been integrated. A plant containing a specific transgene at a specific genomic locus is typically described as containing a specific "event", which is designated by a specific event name. Traits which have been introduced into plants or which have been modified include herbicide tolerance, insect resistance, increased yield, and tolerance to abiotic conditions such as drought.

[0338] Herbicide tolerance has been generated by using mutagenesis and genetic engineering. Plants which have been made tolerant to acetolactate synthase (ALS) inhibitor herbicides by mutagenesis and breeding are, for example, those which are known by the name Available. Herbicide tolerance has been generated via genetic modification to glyphosate, glufosinate, 2,4-D, dicamba, oxynil herbicides (such as bromoxynil and ioxynil), sulfonylurea herbicides, ALS inhibitors, and 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors (such as isoxaflutole and mesotrione).

[0339] Transgenes conferring herbicide tolerance traits include: for glyphosate tolerance: cp4 epsps, epspsgrg23ace5, mepsps, 2mepsps, gat4601, gat4621, goxv247; for glufosinate tolerance: pat and bar; for 2,4-D tolerance: aad-1, aad-12; for dicamba tolerance: dmo; for oxynil herbicide tolerance: bxn; for sulfonylurea herbicide tolerance: zm-hra, csr1-2, gm-hra, S4-HrA; for ALS inhibitor tolerance: csr1-2; and for HPPD inhibitor tolerance: hppdPF, W336, avhppd-03.

[0340] Transgenic maize events containing herbicide tolerance genes include but are not limited to DAS40278, MON801, MON802, MON809, MON810, MON832, MON87411, MON87419, MON87427, MON88017, MON89034, NK603, GA21, MZHG0JG, HCEM485, 676, 678, 680, 33121, 4114, 59122, 98140, Bt10, Bt176, CBH-351, DBT418, DLL25, MS3, MS6, MZIR098, T25, TC1507, and TC6275. Transgenic soybean events containing herbicide tolerance genes include but are not limited to GTS 40-3-2, MON87705, MON87708, MON87712, MON87769, MON89788, A2704-12, A2704-21, A5547-127, A5547-35, DP356043, DAS44406-6, DAS68416-4, DAS-81419-2, GU262, W62, W98, FG72, and CV127. Transgenic cotton events containing herbicide tolerance genes include, but are not limited to, 19-51a, 31707, 42317, 81910, 281-24-236, 3006-210-23, BXN10211, BXN10215, BXN10222, BXN10224, MON1445, MON1698, MON88701, MON88913, GHB119, GHB614, LLCotton25, T303-3, and T304-40. Transgenic canola events containing herbicide tolerance genes are, for example, but not exclusive of others, MON88302, HCR-1, HCN10, HCN28, HCN92, MS1, MS8, PHY14, PHY23, PHY35, PHY36, RF1, RF2, and RF3.

[0341] Transgenics providing insect resistance are preferably toxin genes of Bacillus species and their synthetic variants, such as cry1A, cry1Ab, cry1Ab-Ac, cry1Ac, cry1A.105, cry1F, cry1Fa2, cry2Ab2, cry2Ae, mcry3A, ecry3.1Ab, cry3Bb1, cry34Ab1, cry35Ab1, cry9C, vip3A(a), vip3Aa20. Additionally, transgenics of plant origin can be used, such as genes encoding protease inhibitors, like CpTI and pinII. Another approach uses transgenics such as dvsnf7 to produce double-stranded RNA in plants.

[0342] Transgenic maize events containing insecticidal protein genes or double-stranded RNAs include, but are not limited to, Bt10, Bt11, Bt176, MON801, MON802, MON809, MON810, MON863, MON87411, MON88017, MON89034, 33121, 4114, 5307, 59122, TC1507, TC6275, CBH-351, MIR162, DBT418, and MZIR098. Transgenic soybean events containing insecticidal protein genes include, but are not limited to, MON87701, MON87751, and DAS-81419. Transgenic cotton events containing insecticidal protein genes include, but are not limited to, SGK321, MON531, MON757, MON1076, MON15985, 31707, 31803, 31807, 31808, 42317, BNLA-601, Event1, COT67B, COT102, T303-3, T304-40, GFMCry1A, GK12, MLS 9124, 281-24-236, 3006-210-23, GHB119, and SGK321.

[0343] Cultivated plants with increased yields have been produced by using transgenic athb17 (e.g., maize event MON87403) or bbx32 (e.g., soybean event MON87712).

[0344] Cultivated plants with improved oil content have been produced by using the following transgenes: gm-fad2-1, Pj.D6D, Nc.Fad3, fad2-1A, and fatb1-A (e.g., soybean events 260-05, MON87705, and MON87769).

[0345] Tolerance to abiotic conditions such as drought has been produced by using transgenic cspB (maize event MON87460) and Hahb-4 (soybean event )

[0346] Traits are generally combined by combining genes in a transformation event or by combining different events during a breeding process to produce cultivated plants with stacked traits. Preferred combinations of traits are combinations of herbicide tolerance traits to different groups of herbicides, combinations of insect tolerance to different species of insects, particularly Lepidoptera and Coleoptera insects, combinations of herbicide tolerance with one or several types of insect resistance, combinations of herbicide tolerance with increased yield, and combinations of herbicide tolerance and tolerance to abiotic conditions.

[0347] Plants containing single or stacked traits, as well as the genes and events providing such traits, are well known in the art. For example, detailed information regarding mutagenesis or integration of genes and corresponding events is available from the websites of the organizations "International Service for the Acquisition of Agri-biotech Applications (ISAAA)" (http: / / www.isaaa.org / gmapprovaldatabase) and "Center for Environmental Risk Assessment (CERA)" (http: / / cera-gmc.org / GMCropDatabase). Additional information regarding specific events and methods for detecting such events can be found for Canola events MS1, MS8, RF3, GT73, MON88302, KK179 in WO 01 / 031042, WO 01 / 041558, WO 01 / 041558, WO 02 / 036831, WO 11 / 153186, WO 13 / 003558; for Cotton events MON1445, MON15985, MON531 (MON15985), LLCotton25, MON88913, COT102, 281-24-236, 3006-210-23, COT67B, GHB614, T304-40, GHB119, MON88701, 81910 in WO 02 / 034946, WO 02 / 100163, WO 02 / 100163, WO 03 / 013224, WO 04 / 072235, WO 04 / 039986, WO 05 / 103266, WO 05 / 103266, WO 06 / 128573, WO 07 / 017186, WO 08 / 122406, WO08 / 151780, WO 12 / 134808, WO 13 / 112527;For maize events GA21, MON810, DLL25, TC1507, MON863, MIR604, LY038, MON88017, 3272, 59122, NK603, MIR162, MON89034, 98140, 32138, MON87460, 5307, 4114, MON87427, DAS40278, MON87411, 33121, MON87403, MON87419, reference can be made to WO 98 / 044140, US 02 / 102582, US 03 / 126634, WO 04 / 099447, WO 04 / 011601, WO 05 / 103301, WO 05 / 061720, WO 05 / 059103, WO 06 / 098952, WO 06 / 039376, US2007 / 292854, WO07 / 142840, WO 07 / 140256, WO 08 / 112019, WO 09 / 103049, WO 09 / 111263, WO 10 / 077816, WO11 / 084621, WO 11 / 062904, WO 11 / 022469, WO 13 / 169923, WO 14 / 116854, WO 15 / 053998, WO15 / 142571; for potato events E12, F10, J3, J55, V11, X17, Y9, reference can be made to WO 14 / 178910, WO 14 / 178913, WO 14 / 178941, WO 14 / 179276, WO 16 / 183445, WO 17 / 062831, WO 17 / 062825; for rice events LLRICE06, LLRICE601, LLRICE62, reference can be made to WO 00 / 026345, WO 00 / 026356, WO 00 / 026345;Furthermore, for soybean events H7-1, MON89788, A2704-12, A5547-127, DP305423, DP356043, MON87701, MON87769, CV127, MON87705, DAS68416-4, MON87708, MON87712, SYHT0H2, DAS81419, DAS81419 x DAS44406-6, MON87751, reference can be made to WO 04 / 074492, WO 06 / 130436, WO06 / 108674, WO 06 / 108675, WO 08 / 054747, WO 08 / 002872, WO 09 / 064652, WO 09 / 102873, WO10 / 080829, WO 10 / 037016, WO 11 / 066384, WO 11 / 034704, WO 12 / 051199, WO 12 / 082548, WO13 / 016527, WO 13 / 016516, WO 14 / 201235.;

[0348] The separate use of Compound I and its compositions on cultivated plants can result in effects specific to cultivated plants containing a certain transgene or event. These effects may involve alterations in growth behavior or altered resistance to biotic or abiotic stress factors. Such effects may particularly include increased yield, increased resistance or tolerance to insect, nematode, fungal, bacterial, mycoplasma, viral or viroid pathogens, and early vigour, early or delayed maturity, cold or heat tolerance, and altered amino acid or fatty acid profiles or contents.

[0349] Compound I and its compositions are also suitable for controlling harmful microorganisms in the protection of stored products or harvests and in the protection of materials.

[0350] The term "stored products or harvests" shall be understood to mean natural substances of plant or animal origin and their processed forms required for long-term protection. Stored products of plant origin, such as stalks, leaves, tubers, seeds, fruits or grains, can be protected in the freshly harvested state or in processed forms such as pre-dried, moistened, crushed, ground, pressed or baked (this processing is also referred to as post-harvest treatment). Also falling under the definition of stored products is wood, whether in the form of logs, such as construction timber, electricity transmission towers and fences, or in the form of finished products, such as furniture or objects made of wood. Stored products of animal origin are hides, leather, furs, hairs, etc. Preferably, "stored products" shall be understood to mean natural substances of plant origin and their processed forms, more preferably fruits and their processed forms, such as pome fruits, stone fruits, soft fruits and citrus fruits and their processed forms, wherein the application of compound I and its compositions can also prevent adverse effects such as rot, discoloration or mildew.

[0351] The term "protection of materials" shall be understood to mean protecting technical and non-living materials such as adhesives, glues, wood, paper, cardboard, textiles, leather, paint dispersions, plastics, cooling lubricants, fibres or fabrics against infestation and damage by harmful microorganisms such as fungi and bacteria.

[0352] When used for the protection of materials or stored products, the amount of the active substance applied depends on the type of application area and the desired effect. The amount usually applied for the protection of materials is 0.001 g to 2 kg, preferably 0.005 g to 1 kg of active substance per cubic metre of treated material.

[0353] Compound I and its compositions can be used respectively to improve the health of plants. The present invention also relates to a method for improving the health of plants by treating plants, their propagation materials and / or the sites where plants are growing or will grow with effective amounts of compound I and its compositions respectively.

[0354] The term "plant health" shall be understood to mean the condition of plants and / or their products, which is determined by a number of indicators, either individually or in combination with each other, such as yield (e.g. increased biomass and / or increased content of valuable components), plant vigour (e.g. improved plant growth and / or greener leaves ("greening effect")), quality (e.g. improved content or composition of certain components), and tolerance to abiotic and / or biotic stress. The indicators of plant health status determined above can be interdependent or can influence each other.

[0355] Compound I is used as such or in the form of a composition by treating the following: fungi, plants, plant propagation materials such as seeds; soil, surfaces, materials or rooms that are protected from fungal attack by a fungicidally effective amount of the active substance. Application can be carried out before and after the plant, plant propagation material (such as seeds), soil, surface, material or room is infected with fungi.

[0356] Plant propagation materials can be prophylactically treated with Compound I itself or a composition comprising at least one Compound I at the time of planting or transplanting or before planting or transplanting.

[0357] The present invention also relates to an agrochemical composition comprising an adjuvant and at least one Compound I.

[0358] When used in plant protection, depending on the type of desired effect, the amount of the active substance applied is 0.001 to 2 kg / ha, preferably 0.005 to 2 kg / ha, more preferably 0.05 to 0.9 kg / ha, and especially 0.1 to 0.75 kg / ha.

[0359] In the treatment of plant propagation materials (such as seeds), for example by dusting, coating or soaking, an amount of the active substance of generally 0.1 to 1000 g, preferably 1 to 1000 g, more preferably 1 to 100 g and most preferably 5 to 100 g per 100 kg of plant propagation material (preferably seeds) is required.

[0360] The agrochemical composition comprises a fungicidally effective amount of Compound I. The term "fungicidally effective amount" means an amount of the composition or Compound I that is sufficient to control harmful fungi on cultivated plants, or in the protection of stored products or harvested crops, or in the protection of materials, and that does not cause substantial damage to the treated plants, treated stored products or harvested crops, or to the treated materials. Such amounts can vary widely and depend on various factors such as the fungal species to be controlled, the cultivated plants, stored products, harvested crops or materials being treated, the climatic conditions and the specific Compound I used.

[0361] The user generally applies the agrochemical composition by means of a pre-metering device, a knapsack sprayer, a spray tank, a spray aircraft, or an irrigation system. Generally, the agrochemical composition is made up with water, buffer, and / or other adjuvants to the desired application concentration, and thus a ready-to-use spray liquid or agrochemical composition according to the present invention is obtained. Generally, 20 to 2000 liters, preferably 50 to 400 liters of the ready-to-use spray liquid are applied per hectare of agricultural usable area.

[0362] Compound I, its N-oxides and salts can be converted into agrochemical compositions of common types, such as solutions, emulsions, suspensions, dusts, powders, pastes, granules, tablets, capsules, and mixtures thereof. Examples of composition types (see also "Catalogue of pesticide formulation types and international coding system", Technical Monograph No. 2, 6th Edition, May 2008, CropLife International) are suspensions (e.g., SC, OD, FS), emulsifiable concentrates (e.g., EC), emulsions (e.g., EW, EO, ES, ME), capsules (e.g., CS, ZC), pastes, tablets, wettable powders or dusts (e.g., WP, SP, WS, DP, DS), tablets (e.g., BR, TB, DT), granules (e.g., WG, SG, GR, FG, GG, MG), insecticidal products (e.g., LN), and gel formulations (e.g., GF) for treating plant propagation materials such as seeds. These compositions are prepared in a known manner, such as described by: Mollet and Grubemann, Formulation technology, Wiley VCH, Weinheim, 2001; or Knowles, New developments in crop protection product formulation, Agrow Reports DS243, T&F Informa, London, 2005.

[0363] Suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetting agents, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesives, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, fungicides, antifreezes, antifoaming agents, colorants, tackifiers and binders.

[0364] Suitable solvents and liquid carriers are water and organic solvents such as medium to high boiling mineral oil fractions, for example kerosene, diesel oil; oils of vegetable or animal origin; aliphatic, cycloaliphatic and aromatic hydrocarbons, for example toluene, paraffin wax, tetrahydronaphthalene and alkylated naphthalenes; alcohols, for example ethanol, propanol, butanol, benzyl alcohol, cyclohexanol, ethylene glycol; DMSO; ketones, for example cyclohexanone; esters, for example lactates, carbonates, fatty acid esters, γ-butyrolactone; fatty acids; phosphonates; amines; amides, for example N-methylpyrrolidone, fatty acid dimethylamide; and mixtures thereof.

[0365] Suitable solid carriers or fillers are mineral earths, such as silicates, silica gel, talc, kaolin, limestone, lime, chalk, clay, dolomite, diatomaceous earth, bentonite, calcium sulfate, magnesium sulfate, magnesium oxide; polysaccharides, such as cellulose, starch; fertilizers, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, urea; products of vegetable origin, such as cereal flour, bark powder, wood powder, nut shell powder and mixtures thereof.

[0366] Suitable surfactants are surface-active compounds such as anionic, cationic, non-ionic and amphoteric surfactants, block polymers, polyelectrolytes, and mixtures thereof. Such surfactants can be used as emulsifiers, dispersants, solubilizers, wetting agents, penetration enhancers, protective colloids, or adjuvants. Examples of surfactants are listed in McCutcheon's, Volume 1: Emulsifiers & Detergents, McCutcheon's Directories, Glen Rock, USA, 2008 (International Edition or North American Edition).

[0367] Suitable anionic surfactants are alkali metal salts, alkaline earth metal salts or ammonium salts of sulfonates, sulfates, phosphates, carboxylates and mixtures thereof. Examples of sulfonates are alkylaryl sulfonates, diphenyl sulfonates, α-olefin sulfonates, lignin sulfonates, sulfonates of fatty acids and oils, sulfonates of ethoxylated alkylphenols, sulfonates of alkoxylated arylphenols, sulfonates of condensed naphthalenes, sulfonates of dodecyl and tridecyl benzene, sulfonates of naphthalene and alkylnaphthalenes, sulfosuccinates or sulfosaccharinates. Examples of sulfates are sulfates of fatty acids, sulfates of oils, sulfates of ethoxylated alkylphenols, sulfates of alcohols, sulfates of ethoxylated alcohols, or sulfates of fatty acid esters. Examples of phosphates are phosphate esters. Examples of carboxylates are alkyl carboxylates and carboxylated alcohol or alkylphenol ethoxylates.

[0368] Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants, and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters that have been alkoxylated with 1 to 50 equivalents of alkoxide. Ethylene oxide and / or propylene oxide can be used for alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamides or fatty acid alkanolamides. Examples of esters are fatty acid esters, glycerides or glycerol monoesters. Examples of sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters or alkyl polyglucosides. Examples of polymeric surfactants are homologues or copolymers of vinylpyrrolidone, vinyl alcohol or vinyl acetate.

[0369] Suitable cationic surfactants are quaternary ammonium surfactants, such as quaternary ammonium compounds having one or two hydrophobic groups, or salts of long-chain primary amines. Suitable amphoteric surfactants are alkyl betaines and imidazolines. Suitable block polymers are A-B or A-B-A type block polymers comprising polyethylene oxide and polypropylene oxide blocks, or A-B-C type block polymers comprising alkanol, polyethylene oxide and polypropylene oxide. Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are polyacrylic acid or alkali metal salts of polyacid comb polymers. Examples of polybases are polyvinylamine or polyethylenamine.

[0370] Suitable adjuvants are compounds which themselves have negligible or even no pesticidal activity and which enhance the biological performance of Compound I against the target. Examples are surfactants, mineral or vegetable oils, and other adjuvants. Further examples are listed in Knowles, Adjuvants and additives, Agrow Reports DS256, T&F Informa UK, 2006, Chapter 5.

[0371] Suitable thickeners are polysaccharides (such as xanthan gum, carboxymethyl cellulose), inorganic clays (organo-modified or unmodified), polycarboxylates and silicates.

[0372] Suitable bactericides are bronopol and isothiazolone derivatives, such as alkyl isothiazolones and benzisothiazolones.

[0373] Suitable antifreezes are ethylene glycol, propylene glycol, urea and glycerol.

[0374] Suitable defoamers are silicones, long-chain alcohols, and salts of fatty acids.

[0375] Suitable colorants (e.g., red, blue or green) are low water-soluble pigments and water-soluble dyes. Examples are inorganic colorants (e.g., iron oxide, titanium oxide, iron hexacyanoferrate) and organic colorants (e.g., alizarin, azo and phthalocyanine colorants).

[0376] Suitable thickeners or binders are polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylate, biological wax or synthetic wax, and cellulose ether.

[0377] Agrochemical compositions generally contain from 0.01% to 95% by weight, preferably from 0.1% to 90% by weight, more preferably from 1% to 70% by weight, and especially from 10% to 60% of an active substance (e.g., at least one compound I). Agrochemical compositions generally contain from 5% to 99.9% by weight, preferably from 10% to 99.9% by weight, more preferably from 30% to 99% by weight, and especially from 40% to 90% of at least one adjuvant. The active substance (e.g., compound I) is employed with a purity of 90% to 100%, preferably 95% to 100% (according to NMR spectra).

[0378] For the purpose of treating plant propagation materials, especially seeds, solutions for seed treatment (LS), suspension emulsions (SE), flowable concentrates (FS), powders for dry treatment (DS), water-dispersible powders for slurry treatment (WS), water-soluble powders (SS), emulsions (ES), emulsifiable concentrates (EC) and gels (GF) are generally used. After dilution 2 to 10 times, the concentration of the active substance in the ready-to-use preparation of the composition in question is from 0.01% to 60% by weight, preferably from 0.1% to 40% by weight. Application can be carried out before sowing or during sowing. Methods for applying compound I and its compositions to plant propagation materials, especially seeds, respectively, include dressing, coating, granulation, dusting, soaking and in-furrow application methods. Preferably, compound I or its composition is applied to the plant propagation materials respectively by a method that does not induce germination, such as by dressing, granulation, coating and dusting.

[0379] Various types of oils, wetting agents, adjuvants, fertilizers or micronutrients, and additionally pesticides (e.g., fungicides, growth regulators, herbicides, insecticides, safeners) can be added to compound I or its composition as a premix, or added only until just before use (tank mix). These reagents can be admixed with the composition according to the invention in a weight ratio of 1:100 to 100:1, preferably 1:10 to 10:1.

[0380] Pesticides are generally chemical or biological agents (such as pesticidal active ingredients, compounds, compositions, viruses, bacteria, antimicrobials or disinfectants) that prevent, disable, kill or otherwise frustrate pests through their effects. Target pests can include insects, plant pathogens, weeds, mollusks, birds, mammals, fish, nematodes (roundworms) and microorganisms that damage property, cause nuisances, spread diseases or are vectors of diseases. The term "pesticide" also includes plant growth regulators that alter the expected growth, flowering or reproduction rate of plants; defoliants that cause leaves or other foliage to fall off plants, usually to facilitate harvesting; desiccants that promote the drying of living tissues, such as the above-ground parts of unwanted plants; plant activators that activate plant physiological functions to defend against certain pests; safeners that reduce the unwanted herbicidal effects of pesticides on crop plants; and plant growth promoters that affect plant physiological functions, for example, to enhance plant growth, biomass, yield or any other quality parameter of the harvestable items of crop plants.

[0381] Biopesticides are defined as pesticides based on microorganisms (bacteria, fungi, viruses, nematodes, etc.) or in the form of natural products (compounds such as metabolites, proteins or extracts from biological or other natural sources) (U.S. Environmental Protection Agency: http: / / www.epa.gov / pesticides / biopesticides / ). Biopesticides fall into two main categories, microbial and biochemical pesticides:

[0382] (1) Microbial pesticides consist of bacteria, fungi or viruses (and usually include metabolites produced by bacteria and fungi). Entomopathogenic nematodes are also classified as microbial pesticides, although they are multicellular.

[0383] (2) Biochemical pesticides are naturally occurring substances that control pests or provide other crop protection uses as defined below, but are relatively non-toxic to mammals.

[0384] Mixing compound I or compositions containing them in the form of a fungicide with other fungicides often results in an expanded fungicidal activity spectrum or prevents the development of fungicide resistance. In addition, in many cases, a synergistic effect (synergistic mixture) is obtained.

[0385] The following list of pesticides II that can be used in combination with compound I is intended to illustrate possible combinations but does not limit them:

[0386] A) Respiratory inhibitors

[0387] - At Q o Complex III inhibitors at the Q o site: azoxystrobin (A.1.1), dimoxystrobin (A.1.2), coumoxystrobin (A.1.3), enestroburin (A.1.4), enoxastrobin (A.1.5), enoxamyl (A.1.6), fenoxystrobin / flufenoxystrobin (A.1.7), fluoxastrobin (A.1.8), kresoxim-methyl (A.1.9), mandestrobin (A.1.10), metominostrobin (A.1.11), orysastrobin (A.1.12), picoxystrobin (A.1.13), pyraclostrobin (A.1.14), pyribencarb (A.1.15), pyributicarb (A.1.16), trifloxystrobin (A.1.17), 2-(2-(3-(2,6-dichlorophenyl)-1-methylallylideneaminooxymethyl)phenyl)-2-methoxyimino-N-methyl-acetamide (A.1.18), pyriminobac-methyl (A.1.19), triclopyricarb / chlorodincarb (A.1.20), fenamidone (A.1.21), fenamidone (A.1.21), methyl-N-[2-[(1,4-dimethyl-5-phenylpyrazol-3-yl)oxymethyl]phenyl]-N-methoxy-carbamate (A.1.22), tetraconazole (A.1.25), (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide (A.1.34), (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide (A.1.35), pyridaben (A.1.36), picarbutrazox (A.1.37), 2-(o-((2,5-dimethylphenyloxymethylene)phenyl)-3-methoxy-acrylic acid methyl ester (A.1.38);

[0388] - At Q iComplex III inhibitors at the site: Cyazofamid (A.2.1), Indaziflam (A.2.2), [(6S,7R,8R)-8-benzyl-3-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl] 2-methylpropionate (A.2.3), Picarbutrazox (A.2.4), Fluopicolide (A.2.5), [(1S,2S)-2-(4-fluoro-2-methylphenyl)-1,3-dimethylbutyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(2,4-dimethylphenyl)-1,3-dimethylbutyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate,

[0389] [(1S,2S)-2-(2,4-difluorophenyl)-1,3-dimethylbutyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(2-fluoro-4-methylphenyl)-1,3-dimethylbutyl]

[0390] (2S)-2-[(3-Hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(4-fluoro-2-methylphenyl)-1,3-dimethylbutyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(2,4-dimethylphenyl)-1,3-dimethylbutyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(2,4-difluorophenyl)-1,3-dimethylbutyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(2-fluoro-4-methylphenyl)-1,3-dimethylbutyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, 2-methylpropanoic acid [2-[[(1S)-2-[(1S,2S)-2-(4-fluoro-2-methylphenyl)-1,3-dimethylbutoxy]-1-methyl-2-oxoethyl]carbamoyl]-4-methoxy-3-pyridyl]oxymethyl ester, 2-methylpropanoic acid [2-[[(1S)-2-[(1S,2S)-2-(2,4-dimethylphenyl)-1,3-dimethylbutoxy]-1-methyl-2-oxoethyl]carbamoyl]-4-methoxy-3-pyridyl]oxymethyl ester, 2-methylpropanoic acid [2-[[(1S)-2-[(1S,2S)-2-(2,4-difluorophenyl)-1,3-dimethylbutoxy]-1-methyl-2-oxoethyl]carbamoyl]-4-methoxy-3-pyridyl]oxymethyl ester, 2-methylpropanoic acid [2-[[(1S)-2-[(1S,2S)-2-(2-fluoro-4-methylphenyl)-1,3-dimethylbutoxy]-1-methyl-2-oxoethyl]carbamoyl]-4-methoxy-3-pyridyl]oxymethyl ester, [(1S,2S)-1-methyl-2-(o-tolyl)propyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-1-methyl-2-(o-tolyl)propyl] (2S)-2-[(4-methoxy-3-propionyloxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-1-methyl-2-(o-tolyl)propyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [4-methoxy-2-[[(1S)-1-methyl-2-[(1S,2S)-1-methyl-2-(o-tolyl)propoxy]-2-oxoethyl]carbamoyl]-3-pyridyl] 2-methylpropanoate, [(1S,2S)-2-(2,(2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propanoic acid [2-[(1S,2S)-2-(2,4-dimethylphenyl)-1-methylpropoxy]-1-methyl-2-oxoethyl]amide, [2-[[(1S)-2-[(1S,2S)-2-(2,4-dimethylphenyl)-1-methylpropoxy]-1-methyl-2-oxoethyl]carbamoyl]-4-methoxypyridin-3-yl] 2-methylpropanoate,

[0391] [(1S,2S)-2-(2,4-dimethylphenyl)-1-methyl-propyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(2,6-dimethylphenyl)-1-methyl-propyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [2-[[(1S)-2-[(1S,2S)-2-(2,6-dimethylphenyl)-1-methyl-propoxy]-1-methyl-2-oxo-ethyl]carbamoyl]-4-methoxy-3-pyridyl] 2-methylpropionate, [(1S,2S)-2-(2,6-dimethylphenyl)-1-methyl-propyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-1-methyl-propyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [2-[[(1S)-2-[(1S,2S)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-1-methyl-propoxy]-1-methyl-2-oxo-ethyl]carbamoyl]-4-methoxy-3-pyridyl] 2-methylpropionate, [(1S,2S)-2-[4-fluoro-2-(trifluoromethyl)phenyl]-1-methyl-propyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(4-fluoro-2-methylphenyl)-1-methyl-propyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [2-[[(1S)-2-[(1S,2S)-2-(4-fluoro-2-methylphenyl)-1-methyl-propoxy]-1-methyl-2-oxo-ethyl]carbamoyl]-4-methoxy-3-pyridyl] 2-methylpropionate, [(1S,2S)-2-(4-fluoro-2-methylphenyl)-1-methyl-propyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-1-methyl-2-[2-(trifluoromethyl)phenyl]propyl] (2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]propionate, [4-methoxy-2-[[(1S)-1-methyl-2-[(1S,2S)-1-methyl-2-[2-(trifluoromethyl)phenyl]propoxy]-2-oxo-ethyl]carbamoyl]-3-pyridyl] 2-methylpropionate, [(1S,2S)-1-methyl-2-[2-(trifluoromethyl)phenyl]propyl] (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]propionate, [(1S,2S)-2-(4-fluoro-2,(2S)-2-[(3-acetoxy-4-methoxypyridine-2-carbonyl)amino]-3-(4-fluoro-2,6-dimethylphenyl)-1-methylpropyl propionate, [2-[[(1S)-2-[(1S,2S)-2-(4-fluoro-2,6-dimethylphenyl)-1-methylpropoxy]-1-methyl-2-oxoethyl]carbamoyl]-4-methoxypyridin-3-yl] 2-methylpropionate, (2S)-2-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]-3-(4-fluoro-2,6-dimethylphenyl)-1-methylpropyl propionate;,

[0392] - Complex II inhibitors: carboxin (A.3.1), bixafen (A.3.2), boscalid (A.3.3), boscalid (A.3.4), oxycarboxin (A.3.5), furametpyr (A.3.6), fluxapyroxad (A.3.7), flutolanil (A.3.8), flutriafol (A.3.9), furamorph (A.3.10), isofetamid (A.3.11), isopyrazam (A.3.12), fenfuram (A.3.13), oxycarboxin oxide (A.3.14), fluopyram (A.3.15), pencycuron (A.3.16), fluxametamide (A.3.17), bixafen (A.3.18), sedaxane (A.3.19), tetcyclacis (A.3.20), thifluzamide (A.3.21), indoxacarb (A.3.22), pyriprole (A.3.23), fluindapyr (A.3.28), N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide (A.3.29), methyl (E)-2-[2-[(5-cyano-2-methylphenoxy)methyl]phenyl]-3-methoxyprop-2-enoate (A.3.30), isoflucypram (A.3.31), 2-(difluoromethyl)-N-(1,1,3-trimethylinden-4-yl)nicotinamide (A.3.32), 2-(difluoromethyl)-N-[(3R)-1,1,3-trimethylinden-4-yl]nicotinamide (A.3.33), 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethylinden-4-yl)nicotinamide (A.3.34), 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethylinden-4-yl]nicotinamide (A.3.35), 2-(difluoromethyl)-N-(1,1-dimethyl-3-propylinden-4-yl)nicotinamide (A.3.36), 2-(difluoromethyl)-N-[(3R)-1,1-dimethyl-3-propylinden-4-yl]nicotinamide (A.3.37), 2-(difluoromethyl)-N-(3-isobutyl-1,1-dimethylinden-4-yl)nicotinamide (A.3.38), 2-(difluoromethyl)-N-[(3R)-3-isobutyl-1,1-dimethylinden-4-yl]nicotinamide (A.3.39);

[0393] - Other respiratory inhibitors: diflufenican (A.4.1); nitro-phenyl derivatives: binapacryl (A.4.2), dinobuton (A.4.3), dinocap (A.4.4), fluazinam (A.4.5), dicofol (A.4.6), ferimzone (A.4.7); organo-metallic compounds: triphenyltin salts such as fentin acetate (A.4.8), fentin chloride (A.4.9) or fentin hydroxide (A.4.10); amisulbrom (A.4.11); silthiofam (A.4.12);

[0394] B) Sterol biosynthesis inhibitors (SBI fungicides)

[0395] -C14 demethylase inhibitors: Triazoles: penconazole (B.1.1), bitertanol (B.1.2), bromuconazole (B.1.3), cyproconazole (B.1.4), difenoconazole (B.1.5), diniconazole (B.1.6), diniconazole-M (B.1.7), epoxiconazole (B.1.8), fenbuconazole (B.1.9), fluquinconazole (B.1.10), flusilazole (B.1.11), flutriafol (B.1.12), hexaconazole (B.1.13), imibenconazole (B.1.14), ipconazole (B.1.15), metconazole (B.1.17), myclobutanil (B.1.18), oxpoconazole (B.1.19), paclobutrazol (B.1.20), pefurazoate (B.1.21), propiconazole (B.1.22), prothioconazole (B.1.23),simeconazole (B.1.24), tebuconazole (B.1.25), tetraconazole (B.1.26), triadimefon (B.1.27), triadimenol (B.1.28), triticonazole (B.1.29), uniconazole (B.1.30), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-pyridinyl]propan-2-ol (B.1.31), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]-2-pyridinyl]propan-2-ol (B.1.32), 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 (B.1.33), ipfentrifluconazole (B.1.37), chlorfluzolam (B.1.38), 2-(chloromethyl)-2-methyl-5-[(4-methylbenzyl)methyl]-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol (B.1.43); Imidazoles: imazalil (B.1.44), piperalin (B.1.45), prochloraz (B.1.46), triflumizole (B.1.47); Pyrimidines, pyridines, piperazines: fenarimol (B.1.49), pyrifenox (B.1.50), tridemorph (B.1.51), [3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]-(pyridin-3-yl)methanol (B.1.52),

[0396] 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile (B.1.53), 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (B.1.54), 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (B.1.55);

[0397] -δ14-reductase inhibitors: 4-dodecyl-2,6-dimethylmorpholine (aldimorph) (B.2.1), dodemorph (B.2.2), dodemorph acetate (B.2.3), fenpropimorph (B.2.4), quinomethionate (B.2.5), fenpropidin (B.2.6), tridemorph (B.2.7), spiroxamine (B.2.8);

[0398] -3-ketoreductase inhibitors: fenhexamid (B.3.1);

[0399] -other sterol biosynthesis inhibitors: etaconazole (B.4.1);

[0400] C) Nucleic acid synthesis inhibitors

[0401] -phenylamides or acylamino acid fungicides: benalaxyl (C.1.1), benalaxyl-M (C.1.2), kiralaxyl (C.1.3), metalaxyl (C.1.4), metalaxyl-M (C.1.5), ofurace (C.1.6), oxadixyl (C.1.7);

[0402] -other nucleic acid synthesis inhibitors: hymexazol (C.2.1), octhilinone (C.2.2), oxolinic acid (C.2.3), ethirimol besylate (C.2.4), 5-fluorocytosine (C.2.5), 5-fluoro-2-(p-tolylmethoxy)pyrimidin-4-amine (C.2.6), 5-fluoro-2-(4-fluorophenylmethoxy)pyrimidin-4-amine (C.2.7), 5-fluoro-2-(4-chlorophenylmethoxy)pyrimidin-4-amine (C.2.8);

[0403] D) Cell division and cytoskeleton inhibitors

[0404] - Tubulin inhibitors: benomyl (D.1.1), carbendazim (D.1.2), fuberidazole (D1.3), thiabendazole (D.1.4), thiophanate-methyl (D.1.5), pyridachlometyl (D.1.6), N-ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]butanamide (D.1.8), N-ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methylthio-acetamide (D.1.9), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-(2-fluoroethyl)butanamide (D.1.10), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-(2-fluoroethyl)-2-methoxy-acetamide (D.1.11), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-propyl-butanamide (D.1.12), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methoxy-N-propyl-acetamide (D.1.13), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methylthio-N-propyl-acetamide (D.1.14), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-(2-fluoroethyl)-2-methylthio-acetamide (D.1.15), 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine (D.1.16);

[0405] - Other cell division inhibitors: diethofencarb (D.2.1), ethaboxam (D.2.2), fenfuram (D.2.3), fluopicolide (D.2.4), zoxamide (D.2.5), metrafenone (D.2.6), pyriofenone (D.2.7), cyanotilide (D.2.8);

[0406] E) Amino acid and protein synthesis inhibitors

[0407] - Methionine synthesis inhibitors: cyprodinil (E.1.1), fenarimol (E.1.2), pyrimethanil (E.1.3);

[0408] - Protein synthesis inhibitors: blasticidin-S (E.2.1), kasugamycin (E.2.2), kasugamycin hydrochloride hydrate (E.2.3), validamycin (E.2.4), streptomycin (E.2.5), oxytetracycline (E.2.6);

[0409] F) Signal transduction inhibitors

[0410] -MAP / Histidine kinase inhibitors: fluoroimid (F.1.1), iprodione (F.1.2), procymidone (F.1.3), vinclozolin (F.1.4), fludioxonil (F.1.5);

[0411] -G-protein inhibitors: quinoxyfen (F.2.1);

[0412] G) Lipid and membrane synthesis inhibitors

[0413] -Phospholipid biosynthesis inhibitors: edifenphos (G.1.1), isoprothiolane (G.1.2), iprobenfos (G.1.3), isoprothiolane (G.1.4);

[0414] -Lipid peroxidation: dichlofluanid (G.2.1), quintozene (G.2.2), tecnazene (G.2.3), tolclofos-methyl (G.2.4), biphenyl (G.2.5), chloroneb (G.2.6), ethaboxam (G.2.7), thiazole zinc (G.2.8);

[0415] -Phospholipid biosynthesis and cell wall deposition: dimethomorph (G.3.1), flumorph (G.3.2), mandipropamid (G.3.3), pyrimorph (G.3.4), benthiavalicarb (G.3.5), iprovalicarb (G.3.6), valifenalate (G.3.7);

[0416] -Compounds and fatty acids that affect cell membrane permeability: propamocarb (G.4.1);

[0417] Oxysterol-binding protein inhibitors: flutriafol (G.5.1), fluoxapiprolin (G.5.3), 4-[1-[2-[3-difluoromethyl-5-methyl-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.4), 4-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.5), 4-[1-[2-[3-(difluoromethyl)-5-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.6), 4-[1-[2-[5-cyclopropyl-3-(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.7), 4-[1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.8), 4-[1-[2-[5-(difluoromethyl)-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.9), 4-[1-[2-[3,5-bis(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.10), (4-[1-[2-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidinyl]-N-tetrahydronaphthalen-1-yl-pyridine-2-carboxamide (G.5.11);

[0418] H) Inhibitors with multi-site action

[0419] - Inorganic active substances: Bordeaux mixture (H.1.1), copper (H.1.2), copper acetate (H.1.3), copper hydroxide (H.1.4), copper oxychloride (H.1.5), basic copper sulfate (H.1.6), sulfur (H.1.7);

[0420] - Thio- and dithiocarbamates: ferric dimethyldithiocarbamate (H.2.1), mancozeb (H.2.2), maneb (H.2.3), metam-sodium (H.2.4), metiram (H.2.5), zinc methyldithiocarbamate (H.2.6), thiram (H.2.7), zinc dithiocarbamate (H.2.8), zinc dimethyldithiocarbamate (H.2.9);

[0421] - Organochlorine compounds: anilazine (H.3.1), chlorothalonil (H.3.2), captafol (H.3.3), captan (H.3.4), folpet (H.3.5), dichlofluanid (H.3.6), dichlorophen (H.3.7), hexachlorobenzene (H.3.8), pentachlorophenol (H.3.9) and its salts, tecnazene (H.3.10), tolylfluanid (H.3.11);

[0422] - Guanidine and others: guanidine (H.4.1), dodine (H.4.2), dodine free base (H.4.3), guazatine (H.4.4), guazatine-acetate (H.4.5), guazatine-amine (H.4.6), guazatine-triacetate (H.4.7), bismerthiazol (H.4.8), dithianon (H.4.9), 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone (H.4.10);

[0423] I) Cell wall synthesis inhibitors

[0424] - Glucan synthesis inhibitors: validamycin (I.1.1), polyoxin (I.1.2);

[0425] - Melanin synthesis inhibitors: pyroquilon (I.2.1), tricyclazole (I.2.2), carpropamid (I.2.3), dicyclomet (I.2.4), probenazole (I.2.5);

[0426] J) Plant defense inducers

[0427] - Benzo[1,2,3]thiadiazole-7-carbothioic acid S-methyl ester (J.1.1), thiabendazole (J.1.2), isotianil (J.1.3), tiadinil (J.1.4), prohexadione-calcium (J.1.5); Phosphonates: etridiazole (J.1.6), fosetyl-aluminum (J.1.7), phosphorous acid and its salts (J.1.8), calcium phosphonate (J.1.11), potassium phosphonate (J.1.12), potassium or sodium bicarbonate (J.1.9), 4-cyclopropyl-N-(2,4-dimethoxyphenyl)-1,2,5-thiadiazole-3-carboxamide (J.1.10);

[0428] K) Unknown mode of action

[0429] -Bronopol (K.1.1), Chinomethionat (K.1.2), Cyflufenamid (K.1.3), Cymoxanil (K.1.4), Dazomet (K.1.5), Imibenconazole (K.1.6), Diclocymet (K.1.7), Pyridinitril (K.1.8), Chloridazon (K.1.9), Chloridazon methylsulfate (K.1.10), Diphenylamine (K.1.11), Ethyl chrysanthemate (K.1.12), Amibenzaflox (K.1.13), Fluxapyroxad (K.1.14), Sulfuramid (K.1.15), Fluoxastrobin (K.1.16), Harpin protein (K.1.17), Bensultap (K.1.18), 3,5,6-Trichloro-2-picoline (K.1.19), Phthalide (K.1.20), Trimethacarb (K.1.21), Copper quinolate (K.1.22), Propoxyquilin (K.1.23), Isobutyl ethyl quinolate (K.1.24), Tebupirimfos (K.1.25), Imazamethabenz (K.1.26), N’-(4-(4-Chloro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)-N-ethyl-N-methylformamidine (K.1.27), N’-(4-(4-Fluoro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)-N-ethyl-N-methylformamidine (K.1.28), N’-[4-[[3-[(4-Chlorophenyl)methyl]-1,2,4-thiadiazol-5-yl]oxy]-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine (K.1.29), N’-(5-Bromo-6-indan-2-yloxy-2-methyl-3-pyridyl)-N-ethyl-N-methyl-formamidine (K.1.30), N’-[5-Bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methyl-3-pyridyl]-N-ethyl-N-methyl-formamidine (K.1.31), N’-[5-Bromo-6-(4-isopropylcyclohexyloxy)-2-methyl-3-pyridyl]-N-ethyl-N-methyl-formamidine (K.1.32), N’-[5-Bromo-2-methyl-6-(1-phenylethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine (K.1.33), N’-(2-Methyl-5-trifluoromethyl-4-(3-trimethylsilyl-propoxy)-phenyl)-N-ethyl-N-methylformamidine (K.1.34), N’-(5-Difluoromethyl-2-methyl-4-(3-trimethylsilyl-propoxy)-phenyl)-N-ethyl-N-methylformamidine (K.1.35), 2-(4-Chloro-phenyl)-N-[4-(3,4-dimethoxy-phenyl)-isoxazol-5-yl]-2-prop-2-ynyloxy-acetamide (K.1.36), 3-[5-(4-Chloro-phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine (Pyrifenox) (K.1.37), 3-[5-(4-Methylphenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine (K.1.38), 5-chloro-1-(4,6-dimethoxypyrimidin-2-yl)-2-methyl-1H-benzimidazole (K.1.39), ethyl (Z)-3-amino-2-cyano-3-phenylprop-2-enoate (K.1.40), tetraconazole (K.1.41), pentyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)phenylmethylene]amino]oxymethyl]-2-pyridinyl]carbamate (K.1.42), but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)phenylmethylene]amino]oxymethyl]-2-pyridinyl]carbamate (K.1.43), iproquintazene (K.1.44), fluquinconazole (K.1.47), thiabendazole (K.1.48), bromothalonil (K.1.49), 2-(6-benzyl-2-pyridinyl)quinazoline (K.1.50), 2-[6-(3-fluoro-4-methoxyphenyl)-5-methyl-2-pyridinyl]quinazoline (K.1.51), dichlofluanid (K.1.52), N'-(2,5-dimethyl-4-phenoxyphenyl)-N-ethyl-N-methylformamidine (K.1.53), amisulbrom (K.1.54), fluxapyroxad (K.1.55), N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxyethoxy)-3-pyridinyl]-N-ethyl-N-methylformamidine (K.1.56), N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethylphenyl]-N-ethyl-N-methylformamidine (K.1.57), N-(2-fluorophenyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (K.1.58), N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]thiobenzamide (K.1.59);.

[0430] L) Biopesticides

[0431] L1) Microbial pest control agents with fungicidal, bactericidal, virucidal and / or plant defense activator activities: Ampelomyces quisqualis, Aspergillus flavus, Aureobasidium pullulans, Bacillus altitudinis, Bacillus amyloliquefaciens, Bacillus amyloliquefaciens subsp. plantarum (also known as Bacillus velezensis), Bacillus megaterium, Bacillus mojavensis, Bacillus mycoides, Bacillus pumilus, Bacillus simplex, Bacillus salarius, Bacillus subtilis, Bacillus subtilis var. amyloliquefaciens, Bacillus velezensis, Candida oleophila, Candida saitoana, Clavibacter michiganensis (phage), Coniothyrium minitans, Cryptocline parasitica, Cryptococcus albidus, Dilophosphora alopecuri, Fusarium oxysporum, Clonostachys rosea f. catenulate (also known as Gliocladium catenulatum), Gliocladium roseum, Lysobacter antibioticus, Lysobacter enzymogenes, Metschnikowia fructicola, Microdochium dimerum, Microsphaeropsis arundinis, Muscodor albus, Paenibacillus alvei, Paenibacillus epiphyticus, Paenibacillus polymyxa, Pantoea agglomerans, Penicillium bilaiae, Phellinus igniarius, Pseudomonas spp., Pseudomonas chlororaphis, Pseudozyma flocculosa, Pichia anomala, Pythium oligandrum, Sphaerodes mycoparasitica, Streptomyces griseoviridis, Streptomyces lydicus, Streptomyces violaceusniger, Talaromyces flavus, Trichoderma asperelloides, Trichoderma asperellum, Trichoderma atroviride, Trichoderma apical, Trichoderma gamosum, Trichoderma harzianum, Trichoderma polysporum, Trichoderma stromaticum, Trichoderma virens, Trichoderma viride, Typhula phacorrhiza, Ulocladium oudemansii, Verticillium dahliae, Zucchini yellow mosaic virus (avirulent strain);

[0432] L2) Biochemical pest control agents with fungicidal, bactericidal, virucidal and / or plant defense activator activities: Hypersensitive protein, Reynoutria japonica extract;

[0433] L3) Microbial pest control agents with insecticidal, acaricidal, molluscicidal and / or nematicidal activity: Agrobacterium radiobacter, Bacillus cereus, Bacillus firmus, Bacillus thuringiensis, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. israelensis, Bacillus thuringiensis subsp. galleriae, Bacillus thuringiensis subsp. kurstaki, Bacillus thuringiensis subsp. tenebrionis, Beauveria bassiana, Beauveria brongniartii, Burkholderia species, Chromobacterium subtsugae, Cydia pomonella granulovirus (CpGV), Cryptophlebia leucotreta granulovirus (CrleGV), Flavobacterium species, Helicoverpa armigera nucleopolyhedrovirus (HearNPV), Helicoverpa zea nucleopolyhedrovirus (HzNPV), Helicoverpa zea single nucleocapsid nucleopolyhedrovirus (HzSNPV), Heterorhabditis bacteriophora, Isaria fumosorosea, Lecanicillium longisporum, Lecanicillium muscarium, Metarhizium anisopliae, Metarhizium anisopliae var. anisopliae, Metarhizium anisopliae var. acridum, Nomuraea rileyi, Paecilomyces fumosoroseus, Paecilomyces lilacinus, Paenibacillus popilliae, Pasteuria species, Pasteuria nishizawae, Pasteuria penetrans, Pasteuria ramosa, Pasteuria thornei, Pasteuria usgae, Pseudomonas fluorescens, Spodoptera litura nucleopolyhedrovirus (SpliNPV), Steinernema carpocapsae, Steinernema feltiae, Steinernema sawfly, Streptomyces gilvosporeus, Streptomyces microflavus;

[0434] L4) Biochemical pesticides with insecticidal, acaricidal, molluscicidal, pheromonal and / or nematicidal activity: L-carvone, citral, (E,Z)-7,9-dodecadien-1-yl acetate, ethyl formate, (E,Z)-ethyl 2,4-decadienoate (pear ester), (Z,Z,E)-7,11,13-hexadecatrienal, heptyl butyrate, isopropyl myristate, lavandulyl senecioate, cis-jasmone, 2-methyl-1-butanol, methyleugenol, methyl jasmonate, (E,Z)-2,13-octadecadien-1-ol, (E,Z)-2,13-octadecadien-1-yl acetate, (E,Z)-3,13-octadecadien-1-ol, (R)-1-octen-3-ol, termite pheromone (pentatermanone), (E,Z,Z)-3,8,11-tetradecatrien-1-yl acetate, (Z,E)-9,12-tetradecadien-1-yl acetate, (Z)-7-tetradecen-2-one, (Z)-9-tetradecen-1-yl acetate, (Z)-11-tetradecenal, (Z)-11-tetradecen-1-ol, Chenopodium ambrosiodes extract, neem oil, Quillay extract;

[0435] L5) Microbial pesticides with plant stress reduction, plant growth regulator, plant growth promotion and / or yield increase activity: Azospirillum amazonense, Azospirillum brasilense, Azospirillum lipoferum, Azospirillum iraquense, Azospirillum halopraeferens, Bradyrhizobium spp., Bradyrhizobium elkanii, Bradyrhizobium japonicum, Bradyrhizobium liaoningense, Bradyrhizobium lupini, Delftia acidovorans, arbuscular mycorrhizal fungi, Mesorhizobium spp., Rhizobium leguminosarum biovar phaseoli, Rhizobium leguminosarum biovar trifolii, Rhizobium leguminosarum biovar viciae, Rhizobium tropici, Sinorhizobium meliloti;

[0436] O) Insecticides from classes O.1 to O.29

[0437] O.1 Acetylcholinesterase (AChE) inhibitors: aldicarb, cotton boll carb, benfuracarb, butanone carb, butanone sulfone carb, carbaryl, carbofuran, butanone carb, ethiofencarb, fenbutacarb, fenthiocarb, furamycin, isoprocarb, methiocarb, methomyl, cypermethrin, oxamycin, pirimicarb, propoxur, thiodicarb, long-acting carb, mixed carb, XMC, methiocarb, triazolam; acephate, methyl pyridinium, ethyl azinphos-methyl, azinphos-methyl, cadusin, chlorpyrifos, chlorpyrifos, chlorpyrifos, methyl chlorpyrifos, chlorpyrifos, chlorpyrifos-S-methyl, diazinon, dichlorvos / DDVP, dimethoate, dimethoate, methyl chlorpyrifos, ethyl Amophos, EPN, ethion, propylphos, fenamiphos, fenamiphos, fenitrothion, fenthion, thiamethoxam, heptenephos, cyanimiphos, isopropylamine, O-(methoxyaminothio-phosphoryl) salicylic acid isopropyl ester, isoxathion, malathion, aphidron, methamidophos, methidathion, cypermethrin, monocrotophos, dibromophos, omethoate, sulfone, parathion, methyl parathion, fenthion, phorate, phosalone, phosmet, phosphamidon, phoxim, methyl pirimiphos, propylbromophos, methoprene, propylthion, pyraclofos, pyridazinphos, quinalphos, butyl pirimiphos, bispyribophos, terbufos, chlorpyrifos, methyl ethylsulfonate, triazophos, trichlorfon, aphidron;

[0438] O.2 GABA-gated chloride channel antagonists: endosulfan, chlordane; ethiprole, fipronil, butenefipronil, pyrafluprole, pyriprole;

[0439] O.3 Sodium channel modulators: flumethrin, allethrin, dextro-cis-trans allethrin, dextro-trans allethrin, bifenthrin, k-bifenthrin, bio-allethrin, bio-allethrin S-cyclopentenyl, bio-resmethrin, acetothrin, cypermethrin, β-cypermethrin, flucythrin, λ-cypermethrin, γ-cypermethrin, cypermethrin, α-cypermethrin, β-cypermethrin, θ-cypermethrin, ζ-cypermethrin, phenothrin, deltamethrin, ene Permethrin, cypermethrin, cypermethrin, cypermethrin, flucythrinate, flucythrinate, tau-fluvalinate, bromofluthrin, tefluthrin, imiprothrin, chlorfluthrin, metofluthrin, methoxyfluthrin, ε-methoxyfluthrin, permethrin, phenothrin, pralothrin, profluthrin, pyrethrin (pyrethrum), pyrethrin, silafluthrin, tefluthrin, kappa-tefluthrin, tetrafluthrin, tetramethrin, tralomethrin, transfluthrin; DDT, methoxy-DDT;

[0440] O.4 Nicotinic acetylcholine receptor (nAChR) agonists: acetamiprid, clothianidin, cycloxaprid, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam; 4,5-dihydro-N-nitro-1-(2-oxiranylmethyl)-1H-imidazol-2-amine, (2E)-1-[(6-chloropyridin-3-yl)methyl]-N'-nitro-2-pentylideneamino-guanidine; 1-[(6-chloropyridin-3-yl)methyl]-7-methyl-8-nitro-5-propoxy-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine; nicotine; sulfoxaflor, flupyradifurone, triflumezopyrim, (3R)-3-(2-chlorothiazol-5-yl)-8-methyl-5-oxo-6-phenyl-2,3-dihydrothiazolo[3,2-a]pyrimidin-8-ium-7-phenolate, (3S)-3-(6-chloro-3-pyridinyl)-8-methyl-5-oxo-6-phenyl-2,3-dihydrothiazolo[3,2-a]pyrimidin-8-ium-7-phenolate, (3S)-8-methyl-5-oxo-6-phenyl-3-pyrimidin-5-yl-2,3-dihydrothiazolo[3,2-a]pyrimidin-8-ium-7-phenolate, (3R)-3-(2-chlorothiazol-5-yl)-8-methyl-5-oxo-6-[3-(trifluoromethyl)phenyl]-2,3-dihydrothiazolo[3,2-a]pyrimidin-8-ium-7-phenolate; (3R)-3-(2-chlorothiazol-5-yl)-6-(3,5-dichlorophenyl)-8-methyl-5-oxo-2,3-dihydrothiazolo[3,2-a]pyrimidin-8-ium-7-phenolate, (3R)-3-(2-chlorothiazol-5-yl)-8-ethyl-5-oxo-6-phenyl-2,3-dihydrothiazolo[3,2-a]pyrimidin-8-ium-7-phenolate;

[0441] O.5 Allosteric activators of nicotinic acetylcholine receptors: spinosad, spinetoram;

[0442] O.6 Chloride channel activators: abamectin, emamectin benzoate, ivermectin, lepimectin, milbemycin;

[0443] O.7 Juvenile hormone mimics: hydroprene, kinoprene, methoprene; fenoxycarb, pyriproxyfen;

[0444] O.8 Various non-specific (multi-site) inhibitors: methyl bromide and other alkyl halides; chloropicrin, sulfuryl fluoride, borax, tartar emetic;

[0445] O.9 Chordotonal organ TRPV channel modulators: pymetrozine, flonicamid;

[0446] O.10 Mite growth inhibitors: clofentezine, hexythiazox, flufenzine; etoxazole;

[0447] O.11 Microbial Disruptors of Insect Midgut Membranes: Bacillus thuringiensis, Bacillus sphaericus, and Insecticidal Proteins Produced by Them: Bacillus thuringiensis subsp. israelensis, Bacillus sphaericus, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, Bacillus thuringiensis subsp. tenebrionis, Bt Crop Proteins: Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab, mCry3A, Cry3Ab, Cry3Bb, Cry34 / 35Ab1;

[0448] O.12 Mitochondrial ATP Synthase Inhibitors: Diafenthiuron; Azocyclotin, Cyhexatin, Fenbutatin Oxide, Propargite, Chlorfenson;

[0449] O.13 Oxidative Phosphorylation Uncouplers Interfering via Proton Gradient: Chlorfenapyr, DNOC, Fluethrin;

[0450] O.14 Nicotinic Acetylcholine Receptor (nAChR) Channel Blockers: Bensultap, Cartap, Thiosultap-sodium, Bisultap;

[0451] O.15 Chitin Biosynthesis Inhibitors Type 0: Bistrifluron, Chlorfluazuron, Diflubenzuron, Flucycloxuron, Flufenoxuron, Lufenuron, Novaluron, Teflubenzuron, Triflumuron, Chlorbenzuron, Tralomethrin;

[0452] O.16 Chitin Biosynthesis Inhibitors Type 1: Buprofezin;

[0453] O.17 Molting Disruptors: Cyromazine;

[0454] O.18 Ecdysone Receptor Agonists: Methoxyfenozide, Tebufenozide, Chlorfenapyr, Fufenozide, Chromafenozide;

[0455] O.19 Octopamine Receptor Agonists: Amitraz;

[0456] O.20 Mitochondrial Complex III Electron Transport Inhibitors: Hydramethylnon, Acequinocyl, Fluacrypyrim, Bifenazate;

[0457] O.21 Mitochondrial complex I electron transport inhibitors: fenpyroximate, fenazaquin, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad; rotenone;

[0458] O.22 Voltage-dependent sodium channel blockers: indoxacarb, metaflumizone, 2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]hydrazinecarboxamide, N-(3-chloro-2-methylphenyl)-2-[(4-chlorophenyl)[4-[methyl(methylsulfonyl)amino]phenyl]methylene]hydrazinecarboxamide;

[0459] O.23 Acetyl-CoA carboxylase inhibitors: spirodiclofen, spiromesifen, spirotetramat, methoprene;

[0460] O.24 Mitochondrial complex IV electron transport inhibitors: aluminium phosphide, calcium phosphide, phosphine, zinc phosphide, cyanide;

[0461] O.25 Mitochondrial complex II electron transport inhibitors: cyenopyrafen, cyflumetofen;

[0462] O.26 Ryanodine receptor modulators: flubendiamide, chlorantraniliprole, cyantraniliprole, cyclaniliprole, flonicamid; (R)-3-chloro-N 1 -{2-methyl-4-[1,2,2,2–tetrafluoro-1-(trifluoromethyl)ethyl]phenyl}-N 2 -(1-methyl-2-methylsulfonylethyl)phthalamide, (S)-3-chloro-N 1 -{2-methyl-4-[1,2,2,2–tetrafluoro-1-(trifluoromethyl)ethyl]phenyl}-N 2-(1-Methyl-2-methylsulfonylethyl)phthalamide, methyl-2-[3,5-dibromo-2-({[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}amino)benzoyl]-1,2-dimethylhydrazinecarboxylate; N-[4,6-dichloro-2-[(diethyl-λ4-sulfanylidene)carbamoyl]phenyl]-2-(3-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazole-3-carboxamide; N-[4-chloro-2-[(diethyl-λ4-sulfanylidene)carbamoyl]-6-methylphenyl]-2-(3-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazole-3-carboxamide; N-[4-chloro-2-[(di-2-propyl-λ4-sulfanylidene)carbamoyl]-6-methylphenyl]-2-(3-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazole-3-carboxamide; N-[4,6-dichloro-2-[(di-2-propyl-λ4-sulfanylidene)carbamoyl]phenyl]-2-(3-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazole-3-carboxamide; N-[4,6-dibromo-2-[(diethyl-λ4-sulfanylidene)carbamoyl]phenyl]-2-(3-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazole-3-carboxamide; N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide; 3-chloro-1-(3-chloropyridin-2-yl)-N-[2,4-dichloro-6-[[(1-cyano-1-methylethyl)amino]carbonyl]phenyl]-1H-pyrazole-5-carboxamide; tetrachlorantraniliprole; N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloropyridin-2-yl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide; cyhalodiamide;

[0463] O.27: Chordotonal organ modulators - undefined target site: flonicamid;

[0464] O.28. Insecticidal compounds with unknown or uncertain mode of action: Cyproconazole, Afoxolaner, Azadirachtin, Flufenerim, Bromopropylate, Broflanilide, Bromopropylate, Chinomethionat, Sodium fluoroaluminate, Dicyclanil, Dicofol, Clothianidin, Flucycloxuron, Flometoquin, Flufiprole, Flupyrimin, Fluxametamide, 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(1-oxothietan-3-yl)benzamide, Fluoxastrobin, 5-[3-[2,6-dichloro-4-(3,3-dichloroallyloxy)phenoxy]propoxy]-1H-pyrazole, 4-cyano-N-[2-cyano-5-[[2,6-dibromo-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)propyl]phenyl]carbamoyl]phenyl]-2-methyl-benzamide, 4-cyano-3-[(4-cyano-2-methyl-benzoyl)amino]-N-[2,6-dichloro-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)propyl]phenyl]-2-fluoro-benzamide, N-[5-[[2-chloro-6-cyano-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)propyl]phenyl]carbamoyl]-2-cyano-phenyl]-4-cyano-2-methyl-benzamide, N-[5-[[2-bromo-6-chloro-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]carbamoyl]-2-cyano-phenyl]-4-cyano-2-methyl-benzamide, N-[5-[[2-bromo-6-chloro-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)propyl]phenyl]carbamoyl]-2-cyano-phenyl]-4-cyano-2-methyl-benzamide, 4-cyano-N-[2-cyano-5-[[2,6-dichloro-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)propyl]phenyl]carbamoyl]phenyl]-2-methyl-benzamide;4-Cyano-N-[2-cyano-5-[[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]carbamoyl]phenyl]-2-methyl-benzamide; N-[5-[[2-bromo-6-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]carbamoyl]-2-cyano-phenyl]-4-cyano-2-methyl-benzamide; 2-(1,3-dioxolan-2-yl)-6-[2-(3-pyridyl)-5-thiazolyl]-pyridine; 2-[6-[2-(5-fluoro-3-pyridyl)-5-thiazolyl]-2-pyridyl]-pyrimidine; 2-[6-[2-(3-pyridyl)-5-thiazolyl]-2-pyridyl]-pyrimidine; N-methylsulfonyl-6-[2-(3-pyridyl)thiazol-5-yl]pyridine-2-carboxamide; N-methylsulfonyl-6-[2-(3-pyridyl)thiazol-5-yl]pyridine-2-carboxamide; 1-[(6-chloro-3-pyridyl)methyl]-1,2,3,5,6,7-hexahydro-5-methoxy-7-methyl-8-nitro-imidazo[1,2-a]pyridine; 1-[(6-chloropyridin-3-yl)methyl]-7-methyl-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridin-5-ol; 1-isopropyl-N,5-dimethyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; 1-(1,2-dimethylpropyl)-N-ethyl-5-methyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; N,5-dimethyl-N-pyridazin-4-yl-1-(2,2,2-trifluoro-1-methylethyl)pyrazole-4-carboxamide; 1-[1-(1-cyanocyclopropyl)ethyl]-N-ethyl-5-methyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; N-ethyl-1-(2-fluoro-1-methylpropyl)-5-methyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; 1-(1,2-dimethylpropyl)-N,5-dimethyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; 1-[1-(1-cyanocyclopropyl)ethyl]-N,5-dimethyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; N-methyl-1-(2-fluoro-1-methylpropyl]-5-methyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; 1-(4,4-difluorocyclohexyl)-N-ethyl-5-methyl-N-pyridazin-4-yl-pyrazole-4-carboxamide; 1-(4,4-difluorocyclohexyl)-N,5-dimethyl-N-pyridazin-4-yl-pyrazole-4-carboxamide, N-(1-methylethyl)-2-(3-pyridyl)-2H-indazole-4-carboxamide; N-cyclopropyl-2-(3-pyridyl)-2H-indazole-4-carboxamide; N-cyclohexyl-2-(3-pyridyl)-2H-indazole-4-carboxamide; 2-(3-pyridyl)-N-(2,2,2-trifluoroethyl)-2H-indazole-4-carboxamide;2-(3-Pyridinyl)-N-[(tetrahydro-2-furanyl)methyl]-2H-indazole-5-carboxamide; Methyl 2-[[2-(3-pyridinyl)-2H-indazol-5-yl]carbonyl]hydrazinecarboxylate; N-[(2,2-difluorocyclopropyl)methyl]-2-(3-pyridinyl)-2H-indazole-5-carboxamide; N-(2,2-difluoropropyl)-2-(3-pyridinyl)-2H-indazole-5-carboxamide; 2-(3-Pyridinyl)-N-(2-pyrimidinylmethyl)-2H-indazole-5-carboxamide; N-[(5-methyl-2-pyrazinyl)methyl]-2-(3-pyridinyl)-2H-indazole-5-carboxamide, Tyclopyrazoflor; Sarolaner, Lotilaner, N-[4-chloro-3-[[(phenylmethyl)amino]carbonyl]phenyl]-1-methyl-3-(1,1,2,2,2-pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide; 2-(3-Ethylsulfonyl-2-pyridinyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-5-(trifluoromethyl)-2-pyridinyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, Isoxazoloflutamide, N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-2-methyl-5-(1,1,2,2,2-pentafluoroethyl)-4-(trifluoromethyl)pyrazole-3-carboxamide, N-[4-chloro-3-[(1-cyanocyclopropyl)carbamoyl]phenyl]-2-methyl-5-(1,1,2,2,2-pentafluoroethyl)-4-(trifluoromethyl)pyrazole-3-carboxamide; Acynonapyr; Benzpyrimoxan; Tigolaner;Chloro-N-(1-cyanocyclopropyl)-5-[1-[2-methyl-5-(1,1,2,2,2-pentafluoroethyl)-4-(trifluoromethyl)pyrazol-3-yl]pyrazol-4-yl]benzamide, oxasulfuridin, [(2S,3R,4R,5S,6S)-3,5-dimethoxy-6-methyl-4-propoxytetrahydropyran-2-yl]-N-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]carbamate, [(2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyltetrahydropyran-2-yl]N-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]carbamate, [(2S,3R,4R,5S,6S)-3,5-dimethoxy-6-methyl-4-propoxytetrahydropyran-2-yl]-N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]carbamate, [(2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyltetrahydropyran-2-yl]-N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]carbamate, (2Z)-3-(2-isopropylphenyl)-2-[(E)-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylidenehydrazino]thiazolidin-4-one;2-(6-chloro-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(3-ethylsulfonyl-6-iodo-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(7-chloro-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(3-ethylsulfonyl-7-iodo-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 3-ethylsulfonyl-6-iodo-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridin-2-yl]imidazo[1,2-a]pyridine-8-carbonitrile, 2-[3-ethylsulfonyl-8-fluoro-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoromethylsulfinyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine, 2-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine.;

[0465] The active substance known as component 2, its preparation and its activity, for example against harmful fungi, are known (see: http: / / www.alanwood.net / pesticides / ); these substances are commercially available. Compounds described by the IUPAC nomenclature, their preparation and their pesticidal activity are also known (see Can. J. Plant Sci. [Canadian Journal of Plant Science] 48(6), 587 - 94, 1968; EP - A141 317; EP - A 152 031; EP - A 226 917; EP - A 243 970; EP - A256 503; EP - A 428 941; EP - A 532 022; EP - A1 028 125; EP - A 1 035 122; EP - A 1 201648; EP - A 1 122 244, JP 2002316902; DE 19650197; DE 10021412; DE 102005009458; US3,296,272; US 3,325,503; WO 98 / 46608; WO 99 / 14187; WO 99 / 24413; WO 99 / 27783; WO 00 / 29404; WO 00 / 46148; WO 00 / 65913; WO 01 / 54501; WO 01 / 56358; WO 02 / 22583; WO 02 / 40431; WO 03 / 10149; WO 03 / 11853; WO 03 / 14103; WO 03 / 16286; WO 03 / 53145; WO 03 / 61388; WO 03 / 66609; WO 03 / 74491; WO 04 / 49804; WO 04 / 83193; WO 05 / 120234; WO 05 / 123689; WO 05 / 123690; WO 05 / 63721; WO 05 / 87772; WO 05 / 87773; WO 06 / 15866; WO 06 / 87325; WO 06 / 87343; WO 07 / 82098; WO 07 / 90624, WO 10 / 139271, WO 11 / 028657, WO 12 / 168188, WO 07 / 006670, WO 11 / 77514;WO 13 / 047749, WO 10 / 069882, WO 13 / 047441, WO 03 / 16303, WO 09 / 90181, WO 13 / 007767, WO 13 / 010862, WO 13 / 127704, WO 13 / 024009, WO 13 / 24010, WO 13 / 047441, WO 13 / 162072, WO 13 / 092224, WO 11 / 135833, CN 1907024, CN1456054, CN 103387541, CN 1309897, WO 12 / 84812, CN 1907024, WO 09094442, WO 14 / 60177, WO 13 / 116251, WO 08 / 013622, WO 15 / 65922, WO 94 / 01546, EP 2865265, WO 07 / 129454, WO 12 / 165511, WO 11 / 081174, WO 13 / 47441, WO 16 / 156241, WO 16 / 162265). Some compounds are identified by their CAS Registry Numbers, which are divided into three parts by hyphens, the first part consisting of two to seven digits, the second part consisting of two digits, and the third part consisting of a single digit.;

[0466] According to the present invention, the solid material (dry matter) of biopesticides (except for oils such as neem oil, etc.) is considered to be the active ingredient (obtained, for example, after drying or evaporating the extraction or suspension medium in the case of a liquid formulation of a microbial pesticide). The weight ratios and percentages used for biological extracts such as soapbark extract are based on the total weight of the dry content (solid material) of the corresponding extract.

[0467] The total weight ratio of a composition containing at least one microbial pesticide in the form of live microbial cells (including dormant forms) can be determined by calculating the total weight of the corresponding active ingredient using the amount of CFU of the corresponding microorganism with the following equation: 1×10 10 CFU is equal to the total weight of one gram of the corresponding active ingredient. Colony-forming unit is a measure of live microbial cells. In addition, "CFU" can also be understood as the number of (juvenile) individual nematodes in the case of nematode biopesticides such as Steinernema feltiae.

[0468] In a binary mixture, the weight ratio of component 1) to component 2) usually depends on the properties of the components used, and is usually in the range of 1:10,000 to 10,000:1, often in the range of 1:100 to 100:1, frequently in the range of 1:50 to 50:1, preferably in the range of 1:20 to 20:1, more preferably in the range of 1:10 to 10:1, even more preferably in the range of 1:4 to 4:1, and especially in the range of 1:2 to 2:1. According to a further embodiment, the weight ratio of component 1) to component 2) is usually in the range of 1000:1 to 1:1, often in the range of 100:1 to 1:1, frequently in the range of 50:1 to 1:1, preferably in the range of 20:1 to 1:1, more preferably in the range of 10:1 to 1:1, even more preferably in the range of 4:1 to 1:1, and especially in the range of 2:1 to 1:1. According to a further embodiment, the weight ratio of component 1) to component 2) is usually in the range of 20,000:1 to 1:10, often in the range of 10,000:1 to 1:1, frequently in the range of 5,000:1 to 5:1, preferably in the range of 5,000:1 to 10:1, more preferably in the range of 2,000:1 to 30:1, even more preferably in the range of 2,000:1 to 100:1, and especially in the range of 1,000:1 to 100:1. According to a further embodiment, the weight ratio of component 1) to component 2) is usually in the range of 1:1 to 1:1000, often in the range of 1:1 to 1:100, frequently in the range of 1:1 to 1:50, preferably in the range of 1:1 to 1:20, more preferably in the range of 1:1 to 1:10, even more preferably in the range of 1:1 to 1:4, and especially in the range of 1:1 to 1:2. According to a further embodiment, the weight ratio of component 1) to component 2) is usually in the range of 10:1 to 1:20,000, often in the range of 1:1 to 1:10,000, frequently in the range of 1:5 to 1:5,000, preferably in the range of 1:10 to 1:5,000, more preferably in the range of 1:30 to 1:2,000, even more preferably in the range of 1:100 to 1:2,000, and especially in the range of 1:100 to 1:1,000.

[0469] In a ternary mixture, i.e. a composition comprising component 1) and component 2) and compound III (component 3), the weight ratio of component 1) to component 2) depends on the properties of the active substances used, and is usually in the range of 1:100 to 100:1, frequently in the range of 1:50 to 50:1, preferably in the range of 1:20 to 20:1, more preferably in the range of 1:10 to 10:1, and especially in the range of 1:4 to 4:1, and the weight ratio of component 1) to component 3) is usually in the range of 1:100 to 100:1, frequently in the range of 1:50 to 50:1, preferably in the range of 1:20 to 20:1, more preferably in the range of 1:10 to 10:1, and especially in the range of 1:4 to 4:1. If desired, any additional active component is added to component 1) in a ratio of 20:1 to 1:20. These ratios are also suitable for mixtures applied by seed treatment.

[0470] When a mixture containing a microbial biopesticide is used for crop protection, the application rate ranges from 1×10 6 to 5×10 16 (or greater) CFU / ha, preferably from 1×10 8 to 1×10 13 CFU / ha, and even more preferably from 1×10 9 to 5×10 15 CFU / ha, and especially from 1×10 12 to 5×10 14 CFU / ha. In the case of nematodes as microbial biopesticides (e.g., Steinernema carpocapsae), the application rate range is often from 1×10 5 to 1×10 12 (or greater), preferably from 1×10 8 to 1×10 11 , more preferably from 5×10 8 to 1×10 10 individuals (e.g., in the form of eggs, larvae or any other living stage, preferably in the non-reproductive (infetive) larval stage) / ha.

[0471] When a mixture containing a microbial biopesticide is used for seed treatment, the application rate range is generally from 1×10 6 to 1×10 12 (or greater) CFU / seed, preferably from 1×10 6 to 1×10 9 CFU / seed. In addition, the application rate range for seed treatment is generally from 1×10 7 to 1×10 14 (or greater) CFU / 100 kg of seeds, preferably from 1×10 9 to 1×10 12 CFU / 100 kg of seeds.

[0472] Preferably, a mixture containing at least one active substance as component 2), the at least one active substance being selected from group A) in Q oComplex III inhibitors at the site, more preferably selected from compounds (A.1.1), (A.1.4), (A.1.8), (A.1.9), (A.1.10), (A.1.12), (A.1.13), (A.1.14), (A.1.17), (A.1.21), (A.1.25), (A.1.34) and (A.1.35); particularly selected from (A.1.1), (A.1.4), (A.1.8), (A.1.9), (A.1.13), (A.1.14), (A.1.17), (A.1.25), (A.1.34) and (A.1.35).

[0473] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from the complex III inhibitors in group A) at Q i Complex III inhibitors at the site, more preferably selected from compounds (A.2.1), (A.2.3) and (A.2.4); particularly selected from (A.2.3) and (A.2.4).

[0474] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from the complex II inhibitors in group A), more preferably selected from compounds (A.3.2), (A.3.3), (A.3.4), (A.3.7), (A.3.9), (A.3.11), (A.3.12), (A.3.15), (A.3.16), (A.3.17), (A.3.18), (A.3.19), (A.3.20), (A.3.21), (A.3.22), (A.3.23), (A.3.28), (A.3.31), (A.3.32), (A.3.33), (A.3.34), (A.3.35), (A.3.36), (A.3.37), (A.3.38) and (A.3.39); particularly selected from (A.3.2), (A.3.3), (A.3.4), (A.3.7), (A.3.9), (A.3.12), (A.3.15), (A.3.17), (A.3.19), (A.3.22), (A.3.23), (A.3.31), (A.3.32), (A.3.33), (A.3.34), (A.3.35), (A.3.36), (A.3.37), (A.3.38) and (A.3.39).

[0475] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from other respiratory inhibitors in group A), more preferably selected from compounds (A.4.5) and (A.4.11); particularly (A.4.11).

[0476] Also preferably, a mixture comprising at least one active substance as component 2) is provided, wherein the at least one active substance is selected from the C14 demethylase inhibitors of group B), more preferably selected from compounds (B.1.4), (B.1.5), (B.1.8), (B.1.10), (B.1.11), (B.1.12), (B.1.13), (B.1.17), (B.1.18), (B.1.21), (B.1.22), (B.1.23), (B.1.25), (B.1.26), (B.1.29), (B.1.34), (B.1.37), (B.1.38), (B.1.43), (B.1.46), (B.1.53), (B.1.54) and (B.1.55); particularly preferably selected from (B.1.5), (B.1.8), (B.1.10), (B.1.17), (B.1.22), (B.1.23), (B.1.25), (B.1.33), (B.1.34), (B.1.37), (B.1.38), (B.1.43) and (B.1.46).

[0477] Also preferably, a mixture comprising at least one active substance as component 2) is provided, wherein the at least one active substance is selected from the δ14-reductase inhibitors of group B), more preferably selected from compounds (B.2.4), (B.2.5), (B.2.6) and (B.2.8); particularly (B.2.4).

[0478] Also preferably, a mixture comprising at least one active substance as component 2) is provided, wherein the at least one active substance is selected from the phenylamide and acyl amino acid fungicides of group C), more preferably selected from compounds (C.1.1), (C.1.2), (C.1.4) and (C.1.5); particularly preferably selected from (C.1.1) and (C.1.4).

[0479] Also preferably, a mixture comprising at least one active substance as component 2) is provided, wherein the at least one active substance is selected from the other nucleic acid synthesis inhibitors of group C), more preferably selected from compounds (C.2.6), (C.2.7) and (C.2.8).

[0480] Also preferably, a mixture comprising at least one active substance as component 2) is provided, wherein the at least one active substance is selected from group D), more preferably selected from compounds (D.1.1), (D.1.2), (D.1.5), (D.2.4) and (D.2.6); particularly preferably selected from (D.1.2), (D.1.5) and (D.2.6).

[0481] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group E), more preferably selected from compounds (E.1.1), (E.1.3), (E.2.2) and (E.2.3); in particular (E.1.3).

[0482] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group F), more preferably selected from compounds (F.1.2), (F.1.4) and (F.1.5).

[0483] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group G), more preferably selected from compounds (G.3.1), (G.3.3), (G.3.6), (G.5.1), (G.5.3), (G.5.4), (G.5.5), G.5.6), G.5.7), (G.5.8), (G.5.9), (G.5.10) and (G.5.11); particularly selected from (G.3.1), (G.5.1) and (G.5.3).

[0484] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group H), more preferably selected from compounds (H.2.2), (H.2.3), (H.2.5), (H.2.7), (H.2.8), (H.3.2), (H.3.4), (H.3.5), (H.4.9) and (H.4.10); particularly selected from (H.2.2), (H.2.5), (H.3.2), (H.4.9) and (H.4.10).

[0485] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group I), more preferably selected from compounds (I.2.2) and (I.2.5).

[0486] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group J), more preferably selected from compounds (J.1.2), (J.1.5), (J.1.8), (J.1.11) and (J.1.12); in particular (J.1.5).

[0487] Also preferred is a mixture comprising at least one active substance as component 2), said at least one active substance being selected from group K), more preferably from compounds (K.1.41), (K.1.42), (K.1.44), (K.1.47), (K.1.57), (K.1.58) and (K.1.59); particularly preferably from (K.1.41), (K.1.44), (K.1.47), (K.1.57), (K.1.58) and (K.1.59).

[0488] The biopesticides from group L1) and / or L2) may also have insecticidal, acaricidal, molluscicidal, pheromonal, nematicidal, plant stress reducing, plant growth regulating, plant growth promoting and / or yield increasing activity. The biopesticides from group L3) and / or L4) may also have fungicidal, bactericidal, virucidal, plant defense activating, plant stress reducing, plant growth regulating, plant growth promoting and / or yield increasing activity. The biopesticides from group L5) may also have fungicidal, bactericidal, virucidal, plant defense activating, insecticidal, acaricidal, molluscicidal, pheromonal and / or nematicidal activity.

[0489] Microbial biopesticides, in particular those from groups L1), L3) and L5), include not only isolated pure cultures of the corresponding microorganisms as defined herein, but also their cell-free extracts, their suspensions in whole broth cultures and metabolite-containing media, or purified metabolites obtained from whole broth cultures of the microorganisms.

[0490] Many of these biopesticides are deposited under the accession numbers mentioned herein (prefixes such as ATCC or DSM refer to the initials of the corresponding culture collections, for details see, for example, http: / / www.wfcc.info / ccinfo / collection / by_acronym / ), are mentioned in the literature, are registered and / or are commercially available: a mixture of Aureobasidium pullulans DSM14940 and DSM 14941 was isolated in 1989 in Konstanz, Germany (e.g., blastospores, from ) Bio-Ferm GmbH, Austria), Azospirillum brasilense Sp245 was initially isolated at least before 1980 in the wheat-growing region of southern Brazil (Passo Fundo) (BR 11005; e.g., from Gramineae), Azospirillum brasilense strains Ab-V5 and Ab-V6 (e.g., AzoMax from Novozymes BioAg Produtos para Agricultura Ltda. of Quartel do Lago, Brazil, or from Simbiose-Agro of Brazil Plant Soil 331, 413 - 425, 2010), Bacillus amyloliquefaciens strain AP-188 (NRRL B-50615 and B-50331; US 8,445,255); Bacillus amyloliquefaciens subsp. plantarum strains, sometimes previously also known as Bacillus subtilis, recently reclassified together with Bacillus methylotrophicus and Bacillus velezensis as Bacillus velezensis (Int. J. Syst. Evol. Microbiol. [International Journal of Systematic and Evolutionary Microbiology] 66, 1212–1217, 2016): Bacillus amyloliquefaciens subsp. plantarum or Bacillus velezensis D747 isolated from the air in Kikukawa, Japan (US20130236522 A1; FERM BP-8234; e.g., DoubleNickel TM 55WDG) isolated from soil in Brandenburg, Germany, Bacillus amyloliquefaciens subsp. plantarum or Bacillus velezensis FZB24 (also known as SB3615; DSM 96-2; J. Plant Dis. Prot. [Journal of Plant Diseases and Protection] 105, 181 - 197, 1998; e.g., from Novozyme Biologicals, Inc. of the United States ), Bacillus amyloliquefaciens subsp. plantarum or Bacillus velezensis FZB42 isolated from soil in Brandenburg, Germany (DSM23117; J. Plant Dis. Prot. [Journal of Plant Diseases and Protection] 105, 181 - 197, 1998; e.g., from AbiTEP GmbH of Germany 42), Bacillus amyloliquefaciens subsp. plantarum or Bacillus velezensis MBI600 (also known as 1430; NRRL B-50595; US2012 / 0149571 A1) isolated from broad beans in Sutton Bonington, Nottinghamshire, UK at least before 1988; e.g., from BASF Corporation of the United States ), Bacillus amyloliquefaciens subsp. plantarum or Bacillus velezensis QST-713 (NRRL B-21661; e.g., from Bayer Crop Science LP, USA) isolated from a peach orchard in California, USA in 1995 MAX), Bacillus amyloliquefaciens subsp. plantarum or Bacillus velezensis TJ1000 (also known as 1BE; ATCC BAA-390; CA 2471555 A1; e.g., QuickRoots from TJ Technologies, Watertown, South Dakota, USA) isolated in South Dakota, USA in 1992 TM ); Bacillus firmus CNCM I-1582, a variant of the parental strain EIP-N1 isolated from soil in the Central Region of Israel (CNCM I-1556) (WO 2009 / 126473, US 6,406,690; e.g., from Bayer CropScience LP, USA) ), Bacillus pumilus GHA 180 isolated from the rhizosphere of apple roots in Mexico (IDAC 260707-01; e.g., BX from Premier Horticulture, Quebec, Canada) ), Bacillus pumilus INR-7, also known as BU-F22 and BU-F33, isolated from cucumbers infected with Erwinia tracheiphila at least prior to 1993 (NRRL B-50185, NRRL B-50153; US 8,445,255), Bacillus pumilus KFP9F isolated from the rhizosphere of grass roots in South Africa at least prior to 2008 (NRRL B-50754; WO 2014 / 029697; e.g., BAC-UP or FUSION-P from BASF Agricultural Specialities (Pty) Ltd., South Africa), Bacillus pumilus QST 2808 isolated from soil collected in Pohnpei, Federated States of Micronesia in 1998 (NRRL B-30087; e.g., from Bayer Crop Science LP, USA) or (Plus), Bacillus simplex ABU 288 (NRRL B-50304; US 8,445,255), also known as UD 1022 or UD10-22, Bacillus subtilis FB17 was isolated from red beet root in North America (ATCC PTA-11857; System. Appl. Microbiol. [System and Applied Microbiology] 27, 372-379, 2004; US2010 / 0260735; WO 2011 / 109395); Bacillus thuringiensis subsp. aizawai ABTS-1857 was isolated in 1987 from soil taken from a lawn in Ephraim, Wisconsin, USA (also known as ABG-6346; ATCC SD-1372; e.g., from BioFa AG, Münchingen, Germany of ), Bacillus thuringiensis subsp. kurstaki ABTS-351 is equivalent to HD-1 isolated in 1967 from diseased black larvae of the pink bollworm in Brownsville, Texas, USA (ATCC SD-1275; e.g., from Valent BioSciences, Illinois, USA of DF), Bacillus thuringiensis subsp. kurstaki SB4 was isolated from the larval cadavers of the African sugarcane borer (E. saccharina) (NRRL B-50753; e.g., from BASF Agricultural Specialities (Pty) Ltd., South Africa of Beta ), Bacillus thuringiensis subsp. tenebrionis NB-176-1, a mutant of strain NB-125, was isolated from the dead pupae of the beetle Tenebrio molitor in 1982 (DSM 5480; EP 585 215B1; e.g., from Valent BioSciences, Switzerland of ), Beauveria bassiana GHA (ATCC 74250; e.g., from Laverlam Int. Corp., USA of 22WGP), Beauveria bassiana JW-1 (ATCC 74040; e.g., from CBC (Europe) S.r.l., Italy of ), Beauveria bassiana PPRI 5339 was isolated from the larvae of the tortoise beetle Conchyloctenia punctata (NRRL 50757; e.g., from BASF Agricultural Specialities (Pty) Ltd., South Africa of ),The Bradyrhizobium elkanii strain SEMIA 5019 (also known as 29W) was isolated in Rio de Janeiro, Brazil and SEMIA 587 was isolated in 1967 in the State of Rio Grande do Sul, from an area previously inoculated with North American isolates and has been used for commercial inoculants since 1968 (Appl. Environ. Microbiol. [Applied and Environmental Microbiology] 73(8), 2635, 2007; e.g., GELFIX 5 from BASF Agricultural Specialties Ltd., Brazil), Bradyrhizobium japonicum 532c was isolated from a field in Wisconsin, USA (Nitragin 61A152; Can. J. Plant Sci. [Canadian Journal of Plant Sciences] 70, 661-666, 1990; e.g., (Super), Bradyrhizobium japonicum E-109 variant of strain USDA 138 (INTA E109, SEMIA 5085; Eur. J. Soil Biol. [European Journal of Soil Biology] 45, 28 - 35, 2009; Biol. Fertil. Soils [Biology and Fertility of Soils] 47, 81–89, 2011); Bradyrhizobium japonicum strains known to be deposited at SEMIA by Appl. Environ. Microbiol. [Applied and Environmental Microbiology] 73(8), 2635, 2007: Bradyrhizobium japonicum SEMIA 5079 was isolated from soil by Embrapa-Cerrados in the Cerrados region of Brazil and has been used for commercial inoculants since 1992 (CPAC 15; e.g., GELFIX 5 or ADHERE 60 from BASF Agricultural Specialties Ltd. of Brazil), Bradyrhizobium japonicum SEMIA 5080 was obtained under laboratory conditions by Embrapa-Cerrados in Brazil and has been used for commercial inoculants since 1992 and is a natural variant of SEMIA 586 (CB1809) originally isolated in the United States (CPAC 7; e.g., GELFIX 5 or ADHERE 60 from BASF Agricultural Specialties Ltd. of Brazil); Burkholderia species A396 was isolated from soil in Nikko, Japan in 2008 (NRRL B-50319; WO 2013 / 032693; Marrone Bio Innovations, Inc. of the United States), Coniothyrium minitans CON / M / 91-08 was isolated from Brassica napus (WO 1996 / 021358; DSM 9660; e.g., WG, WG), harpin (α-β) protein (Science [Science] 257, 85 - 88, 1992; e.g., Messenger from Plant Health Care plc of the United Kingdom TM or HARP-N-Tek), Helicoverpa armigera nucleopolyhedrovirus (HearNPV) (J. Invertebrate Pathol [Journal of Invertebrate Pathology]. 107, 112 - 126, 2011; e.g., from Koppert of Brazil from AgBiTech Pty Ltd., Queensland, Australia Max), Helicoverpa zea single nucleocapsid nucleopolyhedrovirus (HzSNPV) (e.g., from Certis LLC, USA ), Helicoverpa zea nucleopolyhedrovirus ABA-NPV-U (e.g., from AgBiTech Pty Ltd., Queensland, Australia ), Heterorhabditis bacteriophora (e.g., from BASF Agricultural Specialities Limited, UK G), Isaria fumosorosea Apopka-97 isolated from mealybugs on Basella alba in Apopka, Florida, USA (ATCC 20874; Biocontrol Science Technol [Biocontrol Science and Technology]. 22(7), 747-761, 2012; e.g., PFR-97 from Certis LLC, USA TM or ), Metarhizium anisopliae var. anisopliae F52, also known as 275 or V275, isolated from Cydia pomonella in Austria (DSM 3884, ATCC 90448; e.g., Novozymes Biologicals BioAg Group, Canada), Metschnikowia fructicola 277 isolated from grapes in central Israel (US 6,994,849; NRRL Y-30752; e.g., previously from Agrogreen, Israel ), Paecilomyces lilacinus 251 isolated from infected nematode eggs in the Philippines (AGAL 89 / 030550; WO 1991 / 02051; Crop Protection [Crop Protection] 27, 352-361, 2008; e.g., from Bayer CropScience AG, Germany and from Certis, USA ), Paenibacillus alvei NAS6G6 was isolated from the rhizosphere of grass roots in South Africa at least before 2008 (WO 2014 / 029697; NRRL B-50755; for example, BAC-UP from BASF Agricultural Specialities (Pty) Ltd., South Africa), Paenibacillus strains isolated from soil samples in various European regions including Germany: Paenibacillus endophyticus Lu17015 (WO 2016 / 020371; DSM 26971), Paenibacillus polymyxa subsp. plantarum Lu16774 (WO 2016 / 020371; DSM 26969), Paenibacillus polymyxa subsp. plantarum strain Lu17007 (WO 2016 / 020371; DSM 26970); Pasteuria nishizawae Pn1 was isolated from a soybean field in Illinois, USA in the mid-2000s (ATCC SD-5833; Federal Register 76(22), 5808, February 2, 2011; for example, Clariva from Syngenta Crop Protection, LLC, USA TM PN), Penicillium bilaiae (also known as P. bilaii) strains ATCC 18309 (= ATCC 74319), ATCC 20851, and / or ATCC 22348 (= ATCC 74318) were originally isolated from soil in Alberta, Canada (Fertilizer Res. 39, 97-103, 1994; Can. J. Plant Sci. 78(1), 91-102, 1998; US5,026,417, WO 1995 / 017806; for example, Jump from Novozymes BioAg Canada ), Reynoutria japonica extract (EP 0307510 B1; for example, SC from Marrone BioInnovations, Davis, CA, USA or ) from BioFa AG, Germany ), Steinernema carpocapsae (for example, ) from BASF Agricultural Specialities Limited, UK ), Streptomyces microflavus NRRL B-50550 (WO 2014 / 124369; Bayer CropScience AG, Germany), Trichoderma asperellum JM41R isolated in South Africa (NRRL 50759; also known as Trichoderma harzianum; e.g., from BASF Agricultural Specialities (Pty) Ltd., South Africa ), Trichoderma harzianum T-22 also known as KRL-AG2 (ATCC 20847; BioControl 57, 687-696, 2012; e.g., from BioWorks Inc., USA or SabrEx from Advanced Biological Marketing Inc., Van Wert, Ohio, USA TM ).

[0491] According to another embodiment of the mixture, at least one pesticidal agent II is selected from groups L1) to L5):

[0492] L1) Microbial pest control agents with fungicidal, bactericidal, virucidal and / or plant defense activator activity: Aureobasidium pullulans DSM 14940 and DSM 14941 (L1.1), Bacillus amyloliquefaciens AP-188 (L.1.2), Bacillus amyloliquefaciens subsp. plantarum D747 (L.1.3), Bacillus amyloliquefaciens subsp. plantarum FZB24 (L.1.4), Bacillus amyloliquefaciens subsp. plantarum FZB42 (L.1.5), Bacillus amyloliquefaciens subsp. plantarum MBI600 (L.1.6), Bacillus amyloliquefaciens subsp. QST-713 (L.1.7), Bacillus amyloliquefaciens subsp. TJ1000 (L.1.8), Bacillus pumilus GB34 (L.1.9), Bacillus pumilus GHA 180 (L.1.10), Bacillus pumilus INR-7 (L.1.11), Bacillus pumilus KFP9F (L.1.12), Bacillus pumilus QST 2808 (L.1.13), Bacillus simplex ABU 288 (L.1.14), Bacillus subtilis FB17 (L.1.15), Coniothyrium minitans CON / M / 91-08 (L.1.16), Metschnikowia fructicola NRRL Y-30752 (L.1.17), Paenibacillus alvei NAS6G6 (L.1.18), Paraburkholderia epiphytica Lu17015 (L.1.25), Paenibacillus polymyxa subsp. plantarum Lu16774 (L.1.26), Paenibacillus polymyxa subsp. strain Lu17007 (L.1.27), Penicillium bilaiae ATCC 22348 (L.1.19), Penicillium bilaiae ATCC 20851 (L.1.20), Penicillium bilaiae ATCC 18309 (L.1.21), Streptomyces microflavus NRRLB-50550 (L.1.22), Trichoderma asperelloides JM41R (L.1.23), Trichoderma harzianum T-22 (L.1.24);

[0493] L2) Biochemical pest control agents with fungicidal, bactericidal, virucidal and / or plant defense activator activity: harpins (L.2.1), Reynoutria maxima extract (L.2.2);

[0494] L3) Microbial pesticidal agents with insecticidal, acaricidal, molluscicidal and / or nematicidal activity: Bacillus firmus I-1582 (L.3.1); Bacillus thuringiensis subsp. aizawai ABTS-1857 (L.3.2), Bacillus thuringiensis subsp. kurstaki ABTS-351 (L.3.3), Bacillus thuringiensis subsp. kurstaki SB4 (L.3.4), Bacillus thuringiensis subsp. tenebrionis NB-176-1 (L.3.5), Beauveria bassiana GHA (L.3.6), Beauveria bassiana JW-1 (L.3.7), Beauveria bassiana PPRI 5339 (L.3.8), Burkholderia species A396 (L.3.9), Helicoverpa armigera nucleopolyhedrovirus (HearNPV) (L.3.10), Heliothis zea nucleopolyhedrovirus (HzNPV) ABA-NPV-U (L.3.11), Heliothis zea single nucleocapsid nucleopolyhedrovirus (HzSNPV) (L.3.12), Heterohabditis bacteriophora (L.3.13), Isaria fumosorosea Apopka-97 (L.3.14), Metarhizium anisopliae var. anisopliae F52 (L.3.15), Paecilomyces lilacinus 251 (L.3.16), Pasteuria nishizawae Pn1 (L.3.17), Steinernema carpocapsae (L.3.18), Steinernema feltiae (L.3.19);

[0495] L4) Biochemical pesticidal agents with insecticidal, acaricidal, molluscicidal, pheromonal and / or nematicidal activity: cis-jasmone (L.4.1), methyl jasmonate (L.4.2), Quillaja saponaria extract (L.4.3);

[0496] L5) Microbial pesticidal agents with plant stress reduction, plant growth regulator, plant growth promotion and / or yield increase activity: Azospirillum brasilense Ab-V5 and Ab-V6 (L.5.1), Azospirillum brasilense Sp245 (L.5.2), Bradyrhizobium elkanii SEMIA 587 (L.5.3), Bradyrhizobium elkanii SEMIA 5019 (L.5.4), Bradyrhizobium japonicum 532c (L.5.5), Bradyrhizobium japonicum E-109 (L.5.6), Bradyrhizobium japonicum SEMIA 5079 (L.5.7), Bradyrhizobium japonicum SEMIA 5080 (L.5.8).

[0497] Furthermore, the present invention relates to agrochemical compositions which comprise a mixture of the following: at least one compound I (component 1) and at least one biopesticide selected from group L) (component 2), in particular at least one biopesticide selected from groups L1) and L2) as described above, and (if desired) at least one suitable adjuvant.

[0498] Furthermore, the present invention relates to agrochemical compositions which comprise a mixture of the following: at least one compound I (component 1) and at least one biopesticide selected from group L) (component 2), in particular at least one biopesticide selected from groups L3) and L4) as described above, and (if desired) at least one suitable adjuvant.

[0499] Also preferred are mixtures which comprise as pesticidal agent II (component 2) a biopesticide selected from groups L1), L3) and L5), preferably selected from the strains designated above as (L.1.2), (L.1.3), (L.1.4), (L.1.5), (L.1.6), (L.1.7), (L.1.8), (L.1.10), (L.1.11), (L.1.12), (L.1.13), (L.1.14), (L.1.15), (L.1.17), (L.1.18), (L.1.19), (L.1.20), L.1.21), (L.1.25), (L.1.26), (L.1.27), (L.3.1); (L.3.9), (L.3.16), (L.3.17), (L.5.1), (L.5.2), (L.5.3), (L.5.4), (L.5.5), (L.5.6), (L.5.7), (L.5.8); (L.4.2) and (L.4.1); even more preferably selected from (L.1.2), (L.1.6), (L.1.7), (L.1.8), (L.1.11), (L.1.12), (L.1.13), (L.1.14), (L.1.15), (L.1.18), (L.1.19), (L.1.20), (L.1.21), (L.3.1); (L.3.9), (L.3.16), (L.3.17), (L.5.1), (L.5.2), (L.5.5), (L.5.6); (L.4.2) and (L.4.1). These mixtures are particularly suitable for treating propagation material, i.e. for seed treatment purposes, and are equally suitable for soil treatment. These seed treatment mixtures are particularly suitable for crops such as cereals, maize and leguminous plants such as soybeans.

[0500] Also preferred are mixtures comprising a biopesticide as pesticidal agent II (component 2), which biopesticide is selected from group L1), L3) and L5), preferably selected from the strains designated above as (L1.1), (L1.2), (L1.3), (L1.6), (L1.7), (L1.9), (L1.11), (L1.12), (L1.13), (L1.14), (L1.15), (L1.17), (L1.18), (L1.22), (L1.23), (L1.24), (L1.25), (L1.26), (L1.27), (L2.2); (L3.2), (L3.3), (L3.4), (L3.5), (L3.6), (L3.7), (L3.8), (L3.10), (L3.11), (L3.12), (L3.13), (L3.14), (L3.15), (L3.18), (L3.19); (L4.2), even more preferably selected from (L1.2), (L1.7), (L1.11), (L1.13), (L1.14), (L1.15), (L1.18), (L1.23), (L3.3), (L3.4), (L3.6), (L3.7), (L3.8), (L3.10), (L3.11), (L3.12), (L3.15) and (L4.2). These mixtures are particularly suitable for the foliar treatment of cultivated plants, preferably vegetables, fruits, vines, cereals, maize and leguminous crops such as soybeans.

[0501] Compositions comprising mixtures of active ingredients can be prepared by customary means, for example by the means given for the compositions of compound I.

[0502] When live microorganisms such as the pesticidal agents II from groups L1), L3) and L5) form part of the composition, such compositions can be prepared by customary means (e.g. H.D. Burges: Formulation of Micobial Biopesticides [Formulation of Microbial Biopesticides], Springer, 1998; WO 2008 / 002371, US 6,955,912, US 5,422,107).

[0503] As explained above, the invention also relates to agrochemical compositions which comprise at least one compound of formula I as defined above, its N-oxide or an agriculturally acceptable salt, and adjuvants, for use against DHODH inhibitor-resistant phytopathogenic fungi as described above. Suitable adjuvants are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetting agents, auxiliaries, solubilizers, penetration enhancers, protective colloids, adhesives, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, fungicides, antifreezes, antifoaming agents, colorants, tackifiers and binders. Suitable solvents, carriers etc. are those described above. In a particular embodiment, the composition additionally comprises at least one further active substance. Suitable further active substances correspond to those described above, in particular those of categories A) to O).

[0504] b) Specific biochemical examples of the claimed use

[0505] According to another embodiment, the invention relates to the use of a compound of formula I as mentioned above, wherein the DHODH inhibitor-resistant phytopathogenic fungus contains in its endogenous DHODH gene at least one, for example 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, in particular 1 to 5, more particularly 1 or 2 mutations which induce resistance, in particular resulting in at least one difference in the amino acid sequence of the mutant DHODH protein relative to the non-mutant DHODH protein, such as substitution, deletion, insertion, inversion.

[0506] The DHODH inhibitor-resistant phytopathogenic fungi can be selected from the group consisting of basidiomycetes, ascomycetes and oomycetes.

[0507] In particular, the DHODH inhibitor-resistant plant pathogenic fungi are selected from the genera of the following group: Alternaria, Bipolaris, Botrytis, Cercospora, Colletotrichum, Corynespora, Fusarium, Plenodomus, Parastagonospora, Monographella, Pseudocercospora, Pyricularia, Pyrenophora, Ramularia, Rhynchosporium, Sclerotinia, Zymoseptoria and Venturia, and more particularly selected from Botrytis, Pyricularia, Sclerotinia and Zymoseptoria.

[0508] More particularly, the DHODH inhibitor-resistant phytopathogenic fungi are selected from the species of the following group: Alternaria, Alternaria solani, Bipolaris sorokiniana, Botrytis cinerea, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f.sp. Lycopersici, Plenodomus lingam, Parastagonospora nodorum, Monilinia laxa, Monographella nivale, Pseudocercospora fijiensis, Pyricularia oryzae, Pyrenophora teres, Pyrenophora tritici-repentis, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, Zymoseptoria tritici and Venturia inaequalis, more particularly selected from the species Botrytis cinerea, Pyricularia oryzae, Sclerotinia sclerotiorum and Zymoseptoria tritici.

[0509] According to another embodiment of the claimed use, the DHODH inhibitor-resistant phytopathogenic fungi contain at least one, for example 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, particularly 1 to 5, more particularly 1 or 2 resistance-inducing mutations in at least one sequence portion in the amino acid sequence of their endogenous non-mutated DHODH enzyme corresponding to one of the following non-mutated consensus sequence motifs (CM) 1 to 6:

[0510] a) X 1 X 2 X3 X 4 X 5 X 6 X 7 R

[0511] (Consensus Motif 1) (SEQ ID NO:52)

[0512] wherein X 1 to X 7 each independently represents any natural proteinogenic amino acid residue and, in particular, has the following meanings:

[0513] X 1 = W, F, Y, H or Del, where Del represents a missing amino acid residue

[0514] X 2 = L, A, I, F or V

[0515] X 3 = V, L, S or A

[0516] X 4 = V, T or P

[0517] X 5 = P, A or M

[0518] X 6 = A, L, V, I, T or F

[0519] X 7 = L, V, M or I

[0520] b) D X 2 E X 4 A H X 7 X 8 G

[0521] (Consensus Motif 2) (SEQ ID NO:53)

[0522] wherein X2 to X8 each independently represents any natural proteinogenic amino acid residue and, in particular, has the following meanings:

[0523] X2 = A, G or P

[0524] X4 = D, E

[0525] X7 = H or Q

[0526] X8 = V, A, F, S or M

[0527] c) L X 2 X 3 X 4 G X6 X 7 X 8 V E

[0528] (Consensus motif 3) (SEQ ID NO:54)

[0529] wherein X2 to X8 independently of one another represent any natural proteinogenic amino acid residue and in particular have the following meanings:

[0530] X2 = F, M or L

[0531] X3 = E, A, D or S

[0532] X4 = L, V or M

[0533] X6 = P or A

[0534] X7 = A or G

[0535] X8 = I or V

[0536] d) X 1 Q X 3 G N X 6 X 7 P R X 10 F R

[0537] (Consensus motif 4) (SEQ ID NO:55)

[0538] wherein X1 to X10 independently of one another represent any natural proteinogenic amino acid residue and in particular have the following meanings:

[0539] X1 = P or A

[0540] X3 = D, E, P, A, L or K

[0541] X6 = P or D

[0542] X7 = K, R or Q

[0543] X10 = V or M

[0544] e) N R Y G X 5 N S

[0545] (Consensus motif 5) (SEQ ID NO:56)

[0546] wherein

[0547] X5 represents any natural proteinogenic amino acid residue and in particular represents L or F

[0548] f) X 1 X 2 X3 YGGX 7 GTX 10 X 11 RX 13 K

[0549] (Consensus Motif 6) (SEQ ID NO:57)

[0550] Wherein X1 to X13 each independently represent any natural proteinogenic amino acid residue, and in particular have the following meanings:

[0551] X1 = A, G, S or K

[0552] X2 = M, L, R or I

[0553] X3 = I, V, M or T

[0554] X7 = A, S, V or P

[0555] X10 = I or V

[0556] X11 = T, G or S

[0557] X13 = I, M or V

[0558] In particular, the order of consensus motifs (CM) 1 to 6 within the corresponding amino acid sequence from the N-terminus to the C-terminus is: CM1-CM2-CM3-CM4-CM5-CM6, where "-" represents a peptide bond, or more particularly and independently represents a single peptide, oligopeptide or polypeptide bridge, for example formed by one or more, such as about 1 to 800, about 1 to 600, about 1 to 300 or about 2 to 70 or about 2 to 10 amino acid residues, for example derivable from Figure 1 alignment.

[0559] According to another embodiment of the claimed use, the endogenous non-mutated DHODH enzyme is selected from the following enzymes, which comprise at least one amino acid sequence selected from SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 or 51, or a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity with any of the said sequences, while retaining DHODH enzyme activity.

[0560] According to a particular embodiment of the use claimed, the DHODH inhibitor-resistant phytopathogenic fungus is of the Botrytis cinerea species and contains at least one, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, particularly 1, 2, 3 or 4, more particularly 1 or 2, and most particularly 1 resistance-inducing mutation in at least particularly 1, 2 or 3, more particularly 1 or 2, and most particularly 1 of the following non-mutated sequence motifs (M) 1 to 6 of its non-mutated DHODH, the non-mutated DHODH comprising the amino acid sequence of SEQ ID NO:1 or a sequence having a degree of sequence identity of at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% thereto:

[0561] a) WLVVPALR (motif 1) corresponding to amino acid residues 91 to 98 of SEQ ID NO:1 (SEQ ID NO:58)

[0562] b) DAEDAHHVG (motif 2) corresponding to amino acid residues 103 to 111 of SEQ ID NO:1 (SEQ ID NO:59)

[0563] c) LFALGPAIVE (motif 3) corresponding to amino acid residues 169 to 178 of SEQ ID NO:1 (SEQ ID NO:60)

[0564] d) AQDGNPKPRVFR (motif 4) corresponding to amino acid residues 186 to 197 of SEQ ID NO:1 (SEQ IDNO:61)

[0565] e) NRYGLNS (motif 5) SEQ ID NO:62 corresponding to amino acid residues 206 to 212 of SEQ ID NO:1

[0566] f) AMVYGGAGTITRIK (motif 6) SEQ IDNO:63 corresponding to amino acid residues 492 to 505 of SEQ ID NO:1

[0567] Particularly, the order of motifs (M) 1 to 6 within the corresponding amino acid sequence from the N-terminus to the C-terminus is: M1-M2-M3-M4-M5-M6, where "-" represents a peptide bond, or more particularly, independently of one another, represents a single peptide, oligopeptide or polypeptide bridge, for example formed by one or more, such as about 1 to 800, about 1 to 600, about 1 to 300 or about 2 to 70 or about 2 to 10 amino acid residues, for example derivable from Figure 1 of the alignment.

[0568] For a more particular use according to the present invention, the DHODH inhibitor-resistant phytopathogenic fungus of the Botrytis cinerea species contains:

[0569] at least one resistance-inducing mutation in Motif 4 (SEQ ID NO: 61) of SEQ ID NO: 1; or

[0570] a combination of at least one resistance-inducing mutation in each (Motif 4) (SEQ ID NO: 61) of SEQ ID NO: 1 and at least one resistance-inducing mutation in Motif 6 (SEQ ID NO: 63); or

[0571] a combination of at least one resistance-inducing mutation in each Motif 4 (SEQ ID NO: 61) of SEQ ID NO: 1 and at least one resistance-inducing mutation in Motif 2 (SEQ ID NO: 59).

[0572] For a very particular use according to the present invention, the DHODH inhibitor-resistant phytopathogenic fungus is of the Botrytis cinerea species and contains at least one resistance-inducing mutation in the non-mutated sequence of SEQ ID NO: 1 or in a sequence having at least 70% identity thereto, wherein the mutant is selected from:

[0573] a) single mutants

[0574] V94X, particularly F, I, L, D, A, G, E or M, more particularly I or L

[0575] A104X, particularly T, P, S, D, V, G or E, more particularly D

[0576] A107X, particularly T, P, S, D, V, G or E, more particularly T or V

[0577] H108X, particularly Q, P, R, L, D, Y or N, more particularly P

[0578] Del109,

[0579] G111X, particularly E, A, V, R, D, C, W or S, more particularly R, V or E

[0580] L172X, particularly F, I, S, V, H, P, R, Q or M, more particularly F

[0581] V195X, particularly F, I, L, D, A, G, E or M, more particularly F, E or D, especially F

[0582] Y208X, particularly S, C, F, N, H or D, more particularly H

[0583] V494X, particularly F, I, L, D, A, G, E or M, more particularly G

[0584] G497X, particularly E, A, V, R, D, C, W or S, more particularly V

[0585] wherein

[0586] Del represents a deletion of an amino acid residue, and

[0587] X represents any natural proteinogenic, particularly any natural proteinogenic amino acid residue that induces resistance; and

[0588] b) Multimutants

[0589] Combinations containing at least 2 of the single mutations that induce resistance as defined above under a), particularly double mutants selected from: V195X / A107X, more particularly V195F / A107V and V195F / A107T; and V195X / V494X, more particularly V195F / V494G

[0590] wherein

[0591] X represents any natural proteinogenic, particularly any natural proteinogenic amino acid residue that induces resistance.

[0592] In yet another embodiment of the use according to the invention, the DHODH inhibitor-resistant phytopathogenic fungi are different from Botrytis cinerea and contain at least one mutation that induces resistance at an amino acid sequence position similar to that of the mutant of the non-mutated Botrytis cinerea DHODH amino acid sequence as defined above in the endogenous DHODH amino acid sequence.

[0593] Particularly, the DHODH inhibitor-resistant phytopathogenic fungi different from Botrytis cinerea are selected from the following species, which are selected from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Plenodomus lini, Phaeosphaeria nodorum, Pellicularia nivale, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora tritici-repentis, Sclerotinia sclerotiorum, Septoria tritici, and Venturia inaequalis.

[0594] Mutants of different fungal species similar to the specific Botrytis cinerea mutants described above can be readily derived from sequence alignments of the corresponding non-mutated endogenous DHODH enzymes of Botrytis cinerea and other fungal species, and identification of the corresponding similar positions to be mutated therein. In the specification Figure 1Examples of suitable alignments are described.

[0595] Accordingly, the following non-limiting examples of similar mutants are given:

[0596] a) The V195X-like mutants are selected from

[0597] the V181X mutant of Alternaria alternata DHODH having the non-mutated amino acid sequence of SEQ ID NO:3

[0598] the V187X mutant of Alternaria solani DHODH having the non-mutated amino acid sequence of SEQ ID NO:5

[0599] the V186X mutant of Bipolaris sorokiniana DHODH having the non-mutated amino acid sequence of SEQ ID NO:11

[0600] the V221X mutant of Cercospora sojina DHODH having the non-mutated amino acid sequence of SEQ ID NO:9

[0601] the V221X mutant of Cercospora beticola DHODH having the non-mutated amino acid sequence of SEQ ID NO:7

[0602] the V185X mutant of Colletotrichum graminicola DHODH having the non-mutated amino acid sequence of SEQ ID NO:13

[0603] the V183X mutant of Colletotrichum orbiculare DHODH having the non-mutated amino acid sequence of SEQ ID NO:15

[0604] the V178X mutant of Corynespora cassiicola DHODH having the non-mutated amino acid sequence of SEQ ID NO:17

[0605] the V179X mutant of Fusarium culmorum DHODH having the non-mutated amino acid sequence of SEQ ID NO:19

[0606] the V179X mutant of Fusarium graminearum DHODH having the non-mutated amino acid sequence of SEQ ID NO:23

[0607] the V179X mutant of Fusarium oxysporum f. sp. lycopersici DHODH having the non-mutated amino acid sequence of SEQ ID NO:21

[0608] the V544X mutant of Elsinoe cruciferarum DHODH having the non-mutated amino acid sequence of SEQ ID NO:25

[0609] The V181X mutant of DHODH from Septoria nodorum with the non-mutated amino acid sequence of SEQ ID NO:27

[0610] The M192X mutant of DHODH from Cladosporium nivalem with the non-mutated amino acid sequence of SEQ ID NO:29

[0611] The V176X mutant of DHODH from Monilinia fructicola with the non-mutated amino acid sequence of SEQ ID NO:49

[0612] The V139X mutant of DHODH from Mycosphaerella fijiensis with the non-mutated amino acid sequence of SEQ ID NO:31

[0613] The V184X mutant of DHODH from Magnaporthe oryzae with the non-mutated amino acid sequence of SEQ ID NO:33

[0614] The V175X mutant of DHODH from Pyrenophora teres with the non-mutated amino acid sequence of SEQ ID NO:35

[0615] The V175X mutant of DHODH from Pyrenophora avenae with the non-mutated amino acid sequence of SEQ ID NO:37

[0616] The V198X mutant of DHODH from Ramularia collo-cygni with the non-mutated amino acid sequence of SEQ ID NO:39

[0617] The V185X mutant of DHODH from Rhynchosporium secalis with the non-mutated amino acid sequence of SEQ ID NO:41

[0618] The V176X mutant of DHODH from Sclerotinia sclerotiorum with the non-mutated amino acid sequence of SEQ ID NO:43

[0619] The V246X mutant of DHODH from Septoria tritici with the non-mutated amino acid sequence of SEQ ID NO:45, and

[0620] The V188X mutant of DHODH from Venturia inaequalis with the non-mutated amino acid sequence of SEQ ID NO:47.

[0621] b) The A107X-like mutants are selected from

[0622] The A99X mutant of DHODH from Magnaporthe oryzae with the non-mutated amino acid sequence of SEQ ID NO:33

[0623] A160X mutant of DHODH of Septoria tritici with a non-mutated amino acid sequence of SEQ ID NO: 45

[0624] For this sequence position, additional similar mutants of DHODH from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Placosphaeria brassicae, Septoria nodorum, Cladosporium herbarum, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, and Venturia inaequalis can be readily derived from Figure 1 the sequence alignment depicted in

[0625] c) The H108X-like mutants are selected from

[0626] the H161X mutant of DHODH of Septoria tritici with a non-mutated amino acid sequence of SEQ ID NO: 45

[0627] For this sequence position, additional similar mutants of DHODH from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Placosphaeria brassicae, Septoria nodorum, Cladosporium herbarum, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, and Venturia inaequalis can be readily derived from Figure 1 the sequence alignment depicted in

[0628] d) The Y208X-like mutants are selected from

[0629] the Y197X mutant of DHODH of Magnaporthe oryzae with a non-mutated amino acid sequence of SEQ ID NO: 33

[0630] For this sequence position, additional similar mutants of DHODH from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Placosphaeria brassicae, Septoria nodorum, Cladosporium herbarum, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, and Venturia inaequalis can be readily derived from Figure 1 the sequence alignment depicted in

[0631] c) Specific examples involving the enzyme mutants of the present invention

[0632] The invention also relates to a mutant DHODH inhibitor-resistant DHODH enzyme as defined above.

[0633] In particular, the invention relates to a DHODH inhibitor-resistant DHODH enzyme obtainable from a phytopathogenic fungus which contains in its endogenous DHODH gene at least one, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, in particular 1 to 5, more particularly 1 or 2 resistance-inducing mutations, in particular leading to at least one difference in the amino acid sequence of the mutant DHODH protein relative to the non-mutant DHODH protein, such as a substitution, deletion, insertion, inversion.

[0634] Such mutant enzymes can be obtained from DHODH inhibitor-resistant phytopathogenic fungi selected from the group consisting of Basidiomycetes, Ascomycetes and Oomycetes.

[0635] In particular, such mutant enzymes can be obtained from DHODH inhibitor-resistant phytopathogenic fungi selected from the genera Alternaria, Bipolaris, Botrytis, Cercospora, Colletotrichum, Corynespora, Fusarium, Gibberella, Leptosphaeria, Mycosphaerella, Pseudocercospora, Pyricularia, Pyrenophora, Ramularia, Rhynchosporium, Sclerotinia, Zymoseptoria and Venturia, more particularly selected from the genera Botrytis, Pyricularia, Sclerotinia and Zymoseptoria, and even more particularly selected from the following fungal species: Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Botrytis cinerea, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Plenodomus lini, Leptosphaeria nodorum, Monilinia fructicola, Monographella nivalis, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, Septoria tritici and Venturia inaequalis, even more particularly selected from the species Botrytis cinerea, Magnaporthe oryzae, Sclerotinia sclerotiorum and Septoria tritici.

[0636] According to another embodiment, a DHODH mutant can be obtained, for example, from a DHODH inhibitor-resistant phytopathogenic fungus which contains in at least one sequence portion of one of the following non-mutant consensus sequence motifs (CM) 1 to 6 corresponding to its endogenous non-mutant amino acid sequence at least one, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, in particular 1 to 5, more particularly 1 or 2 resistance-inducing mutations:

[0637] a) X 1 X2 X 3 X 4 X 5 X 6 X 7 R

[0638] (Consensus Motif 1) (SEQ ID NO:52)

[0639] wherein X 1 to X 7 each independently represents any natural proteinogenic amino acid residue and particularly has the following meanings:

[0640] X 1 = W, F, Y, H or Del, where Del represents a missing amino acid residue

[0641] X 2 = L, A, I, F or V

[0642] X 3 = V, L, S or A

[0643] X 4 = V, T or P

[0644] X 5 = P, A or M

[0645] X 6 = A, L, V, I, T or F

[0646] X 7 = L, V, M or I

[0647] b) D X 2 E X 4 A H X 7 X 8 G

[0648] (Consensus Motif 2) (SEQ ID NO:53)

[0649] wherein X 2 to X 8 each independently represents any natural proteinogenic amino acid residue and particularly has the following meanings:

[0650] X 2 = A, G or P

[0651] X 4 = D, E

[0652] X 7 = H or Q

[0653] X 8 = V, A, F, S or M

[0654] c) L X 2 X 3 X 4 G X 6 X 7 X 8 V E

[0655] (Consensus motif 3) (SEQ ID NO:54)

[0656] wherein X 2 to X 8 each independently represents any naturally occurring proteinogenic amino acid residue and in particular has the following meanings:

[0657] X 2 = F, M or L

[0658] X 3 = E, A, D or S

[0659] X 4 = L, V or M

[0660] X 6 = P or A

[0661] X 7 = A or G

[0662] X 8 = I or V

[0663] d) X 1 Q X 3 G N X 6 X 7 P R X 10 F R

[0664] (Consensus motif 4) (SEQ ID NO:55)

[0665] wherein X 1 to X 10 each independently represents any naturally occurring proteinogenic amino acid residue and in particular has the following meanings:

[0666] X 1 = P or A

[0667] X 3 = D, E, P, A, L or K

[0668] X 6 = P or D

[0669] X 7 = K, R or Q

[0670] X10 = V or M

[0671] e) N R Y G X 5 N S

[0672] (Consensus Motif 5) (SEQ ID NO:56)

[0673] wherein

[0674] X 5 = any natural proteinogenic amino acid residue, and in particular L or F

[0675] f) X 1 X 2 X 3 Y G G X 7 G T X 10 X 11 R X 13 K

[0676] (Consensus Motif 6) (SEQ ID NO:57)

[0677] wherein X 1 to X 13 each independently represents any natural proteinogenic amino acid residue, and in particular has the following meanings:

[0678] X 1 = A, G, S or K

[0679] X2 = M, L, R or I

[0680] X3 = I, V, M or T

[0681] X7 = A, S, V or P

[0682] X10 = I or V

[0683] X11 = T, G or S

[0684] X13 = I, M or V

[0685] In particular, the order of Consensus Motifs (CM) 1 to 6 within the corresponding amino acid sequence is from the N-terminus to the C-terminus: CM1-CM2-CM3-CM4-CM5-CM6, where "-" represents a peptide bond, or more particularly, each independently represents an aminopeptide, oligopeptide or polypeptide bridge, for example formed by one or more, such as about 1 to 800, about 1 to 600, about 1 to 300 or about 2 to 70 or about 2 to 10 amino acid residues, for example derivable from Figure 1 alignment.

[0686] According to another more specific embodiment, the endogenous non-mutated DHODH enzyme is selected from enzymes that comprise at least one amino acid sequence selected from SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 or 51, or a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity with any of said sequences, while retaining DHODH enzyme activity.

[0687] According to an even more specific embodiment, the DHODH mutant can be obtained, for example, from a DHODH inhibitor-resistant phytopathogenic fungus of the Botrytis cinerea species. The mutant contains at least one, particularly 1, 2 or 3, more particularly 1 or 2, and most particularly 1, of the following non-mutated sequence motifs of non-mutated DHODH, and particularly 1, 2, 3 or 4, more particularly 1 or 2, and most particularly 1 resistance-inducing mutation, the non-mutated DHODH comprising the amino acid sequence of SEQ ID NO: 1 or a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity therewith:

[0688] a) WLVVPALR (motif 1) corresponding to amino acid residues 91 to 98 of SEQ ID NO: 1 (SEQ ID NO: 58)

[0689] b) DAEDAHHVG (motif 2) corresponding to amino acid residues 103 to 111 of SEQ ID NO: 1 (SEQ ID NO: 59)

[0690] c) LFALGPAIVE (motif 3) corresponding to amino acid residues 169 to 178 of SEQ ID NO: 1 (SEQ ID NO: 60)

[0691] d) AQDGNPKPRVFR (motif 4) corresponding to amino acid residues 186 to 197 of SEQ ID NO: 1 (SEQ ID NO: 61)

[0692] e) NRYGLNS (motif 5) SEQ ID NO: 62 corresponding to amino acid residues 206 to 212 of SEQ ID NO: 1

[0693] f) AMVYGGAGTITRIK (motif 6) SEQ ID NO: 63 corresponding to amino acid residues 492 to 505 of SEQ ID NO: 1

[0694] In particular, the order of motifs (M) 1 to 6 within the corresponding amino acid sequence from the N-terminus to the C-terminus is: M1 - M2 - M3 - M4 - M5 - M6, where "-" represents a peptide bond, or more particularly, independently of one another, represents a single peptide, oligopeptide or polypeptide bridge, for example formed by one or more, such as about 1 to 800, about 1 to 600, about 1 to 300 or about 2 to 70 or about 2 to 10 amino acid residues, and can be derived, for example, from Figure 1 the alignment of

[0695] According to a very particular embodiment of the invention, the DHODH mutant can be obtained, for example, from an inhibitor-resistant phytopathogenic fungus of the Botrytis cinerea species. It contains

[0696] at least one resistance-inducing mutation in motif 4 (SEQ ID NO: 61) of SEQ ID NO: 1; or

[0697] a combination of at least one resistance-inducing mutation in each motif 4 (SEQ ID NO: 61) of SEQ ID NO: 1 and at least one resistance-inducing mutation in motif 6 (SEQ ID NO: 63); or

[0698] a combination of at least one resistance-inducing mutation in each motif 4 (SEQ ID NO: 61) of SEQ ID NO: 1 and at least one resistance-inducing mutation in motif 2 (SEQ ID NO: 59).

[0699] According to a very particular embodiment, the DHODH mutant can be obtained, for example, from an inhibitor-resistant phytopathogenic fungus of the Botrytis cinerea species. The mutant contains at least one resistance-inducing mutation in the non-mutated sequence of SEQ ID NO: 1 or in a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identity thereto, where the mutant is selected from

[0700] a) single mutants

[0701] V94X, in particular F, I, L, D, A, G, E or M, more particularly I or L

[0702] A104X, in particular T, P, S, D, V, G or E, more particularly D

[0703] A107X, in particular T, P, S, D, V, G or E, more particularly T or V

[0704] H108X, in particular Q, P, R, L, D, Y or N, more particularly P

[0705] Del109,

[0706] G111X, particularly E, A, V, R, D, C, W or S, more particularly R, V or E

[0707] L172X, particularly F, I, S, V, H, P, R, Q or M, more particularly F

[0708] V195X, particularly F, I, L, D, A, G, E or M, more particularly F, E or D, especially F

[0709] Y208X, particularly S, C, F, N, H or D, more particularly H

[0710] V494X, particularly F, I, L, D, A, G, E or M, more particularly G

[0711] G497X, particularly E, A, V, R, D, C, W or S, more particularly V

[0712] wherein

[0713] Del represents a deletion of an amino acid residue, and

[0714] X represents any naturally occurring proteogenic, particularly any naturally occurring proteogenic amino acid residue that induces resistance; and

[0715] b) Multimutants

[0716] Containing a combination of at least 2 of the single mutations that induce resistance as defined above under a),

[0717] Particularly double mutants selected from the following:

[0718] V195X / A107X, more particularly V195F / A107V and V195F / A107T; and

[0719] V195X / V494X, more particularly V195F / V494G

[0720] wherein

[0721] X represents any naturally occurring proteogenic, particularly any naturally occurring proteogenic amino acid residue that induces resistance.

[0722] According to yet another embodiment, additional DHODH mutants different from mutants obtainable from Botrytis cinerea are provided. Such additional mutants contain at least one resistance-inducing mutation in the endogenous DHODH amino acid sequence, at an amino acid sequence position analogous to that of the mutant of the non-mutated Botrytis cinerea DHODH amino acid sequence as defined above.

[0723] In particular, such additional DHODHs different from those obtainable from Botrytis cinerea may be derived from the endogenous DHODHs of the following fungal species, which are selected from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Plenodomus lini, Phaeosphaeria nodorum, Pellicularia nivale, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, Septoria tritici, and Venturia inaequalis.

[0724] DHODH mutants of different fungal species, but analogous to the specific Botrytis cinerea mutants described above, can be readily derived from sequence alignments of the corresponding non-mutated endogenous DHODH enzymes of Botrytis cinerea and the non-mutated DHODHs of other fungal species, and identification of the corresponding analogous positions to be mutated therein. Examples of suitable alignments are described in the Figure 1 specification.

[0725] Therefore, the following non-limiting examples of analogous mutants are given:

[0726] a) V195X analogous mutants selected from

[0727] the V181X mutant of Alternaria alternata DHODH having the non-mutated amino acid sequence of SEQ ID NO:3

[0728] the V187X mutant of Alternaria solani DHODH having the non-mutated amino acid sequence of SEQ ID NO:5

[0729] the V186X mutant of Bipolaris sorokiniana DHODH having the non-mutated amino acid sequence of SEQ ID NO:11

[0730] the V221X mutant of Cercospora sojina DHODH having the non-mutated amino acid sequence of SEQ ID NO:9

[0731] the V221X mutant of Cercospora beticola DHODH having the non-mutated amino acid sequence of SEQ ID NO:7

[0732] The V185X mutant of Colletotrichum graminicola DHODH with the non-mutated amino acid sequence of SEQ ID NO:13

[0733] The V183X mutant of Didymella bryoniae DHODH with the non-mutated amino acid sequence of SEQ ID NO:15

[0734] The V178X mutant of Corynespora cassiicola DHODH with the non-mutated amino acid sequence of SEQ ID NO:17

[0735] The V179X mutant of Fusarium culmorum DHODH with the non-mutated amino acid sequence of SEQ ID NO:19

[0736] The V179X mutant of Fusarium graminearum DHODH with the non-mutated amino acid sequence of SEQ ID NO:23

[0737] The V179X mutant of Fusarium oxysporum f. sp. lycopersici DHODH with the non-mutated amino acid sequence of SEQ ID NO:21

[0738] The V544X mutant of Plenodomus lini DHODH with the non-mutated amino acid sequence of SEQ ID NO:25 and the V181X mutant of Pyrenophora tritici-repentis DHODH with the non-mutated amino acid sequence of SEQ ID NO:27

[0739] The M192X mutant of Cladosporium nivaloides DHODH with the non-mutated amino acid sequence of SEQ ID NO:29

[0740] The V176X mutant of Monilinia fructicola DHODH with the non-mutated amino acid sequence of SEQ ID NO:49

[0741] The V139X mutant of Mycosphaerella fijiensis DHODH with the non-mutated amino acid sequence of SEQ ID NO:31 and the V184X mutant of Magnaporthe oryzae DHODH with the non-mutated amino acid sequence of SEQ ID NO:33

[0742] The V175X mutant of Pyrenophora teres DHODH with the non-mutated amino acid sequence of SEQ ID NO:35

[0743] The V175X mutant of Pyrenophora avenae DHODH with the non-mutated amino acid sequence of SEQ ID NO:37

[0744] The V198X mutant of Ramularia collo-cygni DHODH with the non-mutated amino acid sequence of SEQ ID NO:39

[0745] The V185X mutant of DHODH from Rhynchosporium secalis with the non-mutated amino acid sequence of SEQ ID NO:41

[0746] The V176X mutant of DHODH from Sclerotinia sclerotiorum with the non-mutated amino acid sequence of SEQ ID NO:43

[0747] The V246X mutant of DHODH from Septoria tritici with the non-mutated amino acid sequence of SEQ ID NO:45, and

[0748] The V188X mutant of DHODH from Venturia inaequalis with the non-mutated amino acid sequence of SEQ ID NO:47.

[0749] b) The A107X-like mutants are selected from

[0750] The A99X mutant of DHODH from Magnaporthe oryzae with the non-mutated amino acid sequence of SEQ ID NO:33

[0751] The A160X mutant of DHODH from Septoria tritici with the non-mutated amino acid sequence of SEQ ID NO:45

[0752] For this specific sequence, additional similar mutants of DHODH from Alternaria spp., Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Plenodomus lini, Phaeosphaeria nodorum, Pythium nunn, Monilinia fructicola, Pseudocercospora musae, Pyrenophora teres, Rhynchosporium secalis, Sclerotinia sclerotiorum and Venturia inaequalis can be readily derived from Figure 1 the sequence alignment depicted in

[0753] c) The H108X-like mutants are selected from

[0754] The H161X mutant of DHODH from Septoria tritici with the non-mutated amino acid sequence of SEQ ID NO:45.

[0755] For this particular sequence, additional similar mutants of DHODH from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f.sp. lycopersici, Elsinoe cruciferarum, Leptosphaeria nodorum, Cladosporium herbarum, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, and Venturia inaequalis can be readily derived from Figure 1 the sequence alignment depicted in

[0756] d) The Y208X-like mutants are selected from

[0757] the Y197X mutant of Magnaporthe oryzae DHODH having the non-mutated amino acid sequence of SEQ ID NO:45

[0758] For this particular sequence, additional similar mutants of DHODH from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f.sp. lycopersici, Elsinoe cruciferarum, Leptosphaeria nodorum, Cladosporium herbarum, Monilinia fructicola, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, and Venturia inaequalis can be readily derived from Figure 1 the sequence alignment depicted in

[0759] Although the above-mentioned embodiments have been described based on the DHODH enzyme of Botrytis cinerea in the long version according to SEQ ID NO:1, there is also a short version of the enzyme in which the amino-terminal portion of 19 residues is missing and is described herein as SEQ ID NO:51. In this short version, for example, position V195 of the long version corresponds to V176. The numbering of other specific sequence positions will change accordingly.

[0760] Another embodiment of the present invention relates to a nucleic acid molecule comprising at least one nucleotide sequence encoding a mutant DHODH enzyme as defined above, in particular a mutant nucleic acid sequence selected from nucleotide sequences derived from SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 and sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to any of the said sequences, and the nucleic acid molecule comprises at least one mutation in the nucleotide sequence encoding the mutant DHODH enzyme.

[0761] Yet another embodiment of the present invention relates to an expression construct comprising at least one nucleic acid molecule comprising at least one nucleotide sequence encoding a mutant DHODH enzyme as defined above, in particular a mutant nucleic acid sequence selected from nucleotide sequences derived from SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 and sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to any of the said sequences, and the nucleic acid molecule comprises at least one mutation in the nucleotide sequence encoding the mutant DHODH enzyme.

[0762] Another embodiment of the present invention provides a vector comprising at least one nucleic acid molecule comprising at least one nucleotide sequence encoding a mutant DHODH enzyme as defined above, in particular a mutant nucleic acid sequence selected from nucleotide sequences derived from SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 and sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to any of the said sequences, and the nucleic acid molecule comprises at least one mutation in the nucleotide sequence encoding the mutant DHODH enzyme; or at least one expression construct comprising at least one such coding nucleotide sequence.

[0763] Another embodiment of the present invention provides a natural or non-natural recombinant microbial host or host cell comprising at least one such nucleic acid molecule, or at least one such expression construct or at least one vector, each comprising at least one nucleic acid molecule comprising at least one nucleotide sequence encoding a mutant DHODH enzyme as defined above, in particular selected from nucleotide sequences derived from SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 and mutant nucleic acid sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity with any of said sequences

[0764] In another embodiment, the present invention provides a method for combating phytopathogenic fungi selected from the genera Alternaria, Bipolaris, Botrytis, Cercospora, Colletotrichum, Corynespora, Fusarium, Gibberella, Leptosphaeria, Mycosphaerella, Pseudocercospora, Pyricularia, Pyrenophora, Rhynchosporium, Sclerotinia, Zymoseptoria and Venturia, more particularly selected from the genera Botrytis, Pyricularia, Sclerotinia and Zymoseptoria, more particularly the phytopathogenic fungi selected from Alternaria alternata, Alternaria solani, Bipolaris sorokiniana, Botrytis cinerea, Cercospora sojina, Cercospora beticola, Colletotrichum graminicola, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium culmorum, Fusarium graminearum, Fusarium oxysporum f. sp. lycopersici, Plenodomus lini, Leptosphaeria nodorum, Monilinia fructicola, Mycosphaerella nivale, Pseudocercospora musae, Magnaporthe oryzae, Pyrenophora teres, Pyrenophora avenae, Ramularia collo-cygni, Rhynchosporium secalis, Sclerotinia sclerotiorum, Septoria tritici and Venturia inaequalis, more particularly selected from the species Botrytis cinerea, Magnaporthe oryzae, Sclerotinia sclerotiorum and Septoria tritici

[0765] The method comprises:

[0766] treating these phytopathogenic fungi or materials, plants, soil or seeds at risk of being diseased due to said phytopathogenic fungi with an effective amount of at least one compound of formula I as defined above or a composition comprising the same

[0767] More particularly, the method comprises:

[0768] c) identifying said phytopathogenic fungi or materials, plants, soil or seeds at risk of being diseased due to said phytopathogenic fungi;

[0769] and

[0770] d) treating the fungus or the material, plant, soil or seed with an effective amount of at least one compound of formula I as defined above or a composition comprising the same.

[0771] Yet another embodiment of the present invention relates to a screening method for identifying DHODH inhibitor compounds suitable for combating DHODH inhibitor-resistant phytopathogenic fungi, the method comprising contacting a DHODH inhibitor-resistant phytopathogenic fungus or its spores capable of expressing a DHODH enzyme mutant as defined above with at least one chemical or biochemical molecule suspected of exerting inhibitory activity against such a fungus, culturing the fungus or its spores in the presence of the at least one chemical or biochemical molecule, and determining the growth ability of the fungus culture.

[0772] d) Additional more general biochemical examples

[0773] 1. The polypeptides of the present invention

[0774] In this context, the following definitions apply:

[0775] The general terms "polypeptide" or "peptide", which may be used interchangeably, refer to a natural or synthetic linear chain or sequence of amino acid residues with contiguous peptide linkages, containing from about 10 to up to more than 1,000 residues. Short-chain polypeptides with up to 30 residues are also designated as "oligopeptides".

[0776] The term "protein" refers to a macromolecular structure composed of one or more polypeptides. The amino acid sequence of one or more of its polypeptides represents the "primary structure" of the protein. This amino acid sequence also pre-determines the "secondary structure" of the protein by forming special structural elements such as α-helices and β-sheet structures formed within the polypeptide chain. The arrangement of multiple such secondary structural elements defines the "tertiary structure" or spatial arrangement of the protein. If a protein contains more than one polypeptide chain, the chains are arranged in space to form the "quaternary structure" of the protein. The correct spatial arrangement or "folding" of a protein is a prerequisite for protein function. Denaturation or unfolding destroys protein function. If such destruction is reversible, protein function can be restored by refolding.

[0777] A typical protein function mentioned herein is "enzymatic function", i.e., the protein acts as a biocatalyst on a substrate (e.g., a compound) and catalyzes the conversion of the substrate into a product. Enzymes can exhibit a high or low degree of substrate and / or product specificity.

[0778] Thus, a "polypeptide" referred to herein as having a specific "activity" implicitly refers to a correctly folded protein that exhibits the indicated activity (e.g., a specific enzymatic activity).

[0779] Accordingly, unless otherwise indicated, the term "polypeptide" also encompasses the terms "protein" and "enzyme".

[0780] Similarly, the term "polypeptide fragment" encompasses the terms "protein fragment" and "enzyme fragment".

[0781] The term "isolated polypeptide" refers to an amino acid sequence that has been removed from its natural environment by any method or combination of methods known in the art and includes recombinant, biochemical, and synthetic methods.

[0782] The present invention also relates to "functional equivalents" (also designated as "analogs" or "functional mutants") of the polypeptides specifically described herein.

[0783] For example, a "functional equivalent" is a polypeptide that exhibits at least 1% to 10%, or at least 20%, or at least 50%, or at least 75%, or at least 90% higher or lower activity than the polypeptides specifically described herein in a test for determining the enzyme activity (specifically DHODH activity) mentioned herein.

[0784] According to the present invention, "functional equivalents" also encompass specific mutants that have an amino acid different from the specifically stated amino acid at at least one sequence position of the amino acid sequence described herein but still have one of the above-mentioned biological activities (such as enzyme activity). Thus, "functional equivalents" include mutants that can be obtained by one or more, such as 1 to 20, particularly 1 to 15, or 5 to 10 amino acid additions, substitutions (especially conservative substitutions), deletions, and / or inversions, where the alterations can occur at any sequence position, provided that they produce mutants having the characteristic profile according to the present invention. If the activity pattern is qualitatively consistent between the mutant and the unaltered polypeptide, i.e., if, for example, an interaction with the same agonist or antagonist or substrate is observed, but the rate (i.e., represented by the EC 50 or IC 50 value or any other suitable parameter in the art) is different, then functional equivalence is also particularly provided. Examples of suitable (conservative) amino acid substitutions are shown in the following table:

[0785]

[0786]

[0787] "Functional equivalents" in the above sense are also "precursors" of the polypeptides described herein, as well as "functional derivatives" and "salts" of the polypeptides.

[0788] In this case, a "precursor" is a natural or synthetic precursor of a polypeptide that may or may not have the desired biological activity.

[0789] The term "salt" means the salts of the carboxyl groups and the acid addition salts of the amino groups of the protein molecules according to the present invention. The salts of the carboxyl groups can be produced in a known manner and include inorganic salts, such as sodium salts, calcium salts, ammonium salts, iron salts and zinc salts, as well as salts with organic bases, such as amines such as triethanolamine, arginine, lysine, piperidine, etc. The present invention also encompasses acid addition salts, such as salts with inorganic acids (such as hydrochloric acid or sulfuric acid) and salts with organic acids (such as acetic acid and oxalic acid).

[0790] "Functional derivatives" of the polypeptides according to the present invention can also be produced using known techniques on the functional amino acid side groups or at their N-terminus or C-terminus. Such derivatives include, for example, aliphatic esters of carboxylic acid groups, amides of carboxylic acid groups, which can be obtained by reaction with ammonia or with primary or secondary amines; N-acyl derivatives of free amino groups, produced by reaction with acyl groups; or O-acyl derivatives of free hydroxyl groups, produced by reaction with acyl groups.

[0791] "Functionally equivalent" naturally occurring fluids include polypeptides that can be obtained from other organisms, as well as naturally occurring variants. For example, regions of homologous sequence regions can be established by sequence comparison, and equivalent polypeptides can be determined based on the specific parameters of the present invention.

[0792] "Functionally equivalent" also includes "fragments", such as individual domains or sequence motifs of the polypeptides according to the present invention, or N- and / or C-terminal truncated forms, which may or may not exhibit the desired biological function. In particular, such "fragments" retain at least qualitatively the desired biological function.

[0793] Furthermore, "functionally equivalent" are also fusion proteins that have one of the polypeptide sequences described herein or a functionally equivalent derived therefrom and at least one additional functionally different heterologous sequence, which is associated at the functional N-terminus or C-terminus (i.e., without substantial mutual functional impairment of the fusion protein part). Non-limiting examples of such heterologous sequences are, for example, signal peptides, histidine anchors or enzymes.

[0794] "Functionally equivalent" as further included according to the invention are homologs of the specifically disclosed polypeptides. These homologs have at least 60%, particularly at least 75%, particularly at least 80% or 85%, such as 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homology (or identity) with one of the specifically disclosed amino acid sequences, calculated by the algorithm of Pearson and Lipman, Proc. Natl. Acad. Sci. (USA) 85(8), 1988, 2444-2448. The homology or identity (expressed as a percentage) of the homologous polypeptides according to the invention particularly means the identity (expressed as a percentage) of amino acid residues based on the total length of one of the amino acid sequences specifically described herein.

[0795] Identity data expressed as a percentage can also be determined by means of BLAST alignment, the algorithm blastp (protein-protein BLAST) or by applying the Clustal settings specified below.

[0796] In the case of possible protein glycosylation, "functionally equivalent" according to the invention includes polypeptides in deglycosylated or glycosylated form as described herein, as well as modified forms that can be obtained by altering the glycosylation pattern.

[0797] Functionally equivalent or homologous polypeptides according to the invention can be generated by mutagenesis, for example by point mutation, extension or shortening of the protein, or as described in more detail below.

[0798] Functionally equivalent or homologous polypeptides according to the invention can be identified by screening a combinatorial library of mutants (e.g., shortened mutants). For example, a diversified library of protein variants can be generated by combinatorial mutagenesis at the nucleic acid level (e.g., by enzymatic ligation to synthesize a mixture of oligonucleotides). There are many methods available for generating a library of potential homologs from degenerate oligonucleotide sequences. Chemical synthesis of degenerate gene sequences can be carried out in an automated DNA synthesizer, and then the synthetic genes can be ligated into a suitable expression vector. The use of degenerate genomic libraries enables all sequences encoding the desired set of potential protein sequences to be provided in a mixture. Methods for the synthesis of degenerate oligonucleotides are known to those skilled in the art.

[0799] In the prior art, several techniques are known for screening gene products of combinatorial databases generated by point mutations or truncations, and for screening cDNA libraries for gene products with selected properties. These techniques can be adapted to rapidly screen gene libraries generated by combinatorial mutagenesis of homologs according to the present invention. Based on high-throughput analysis, the techniques most commonly used for screening large gene libraries include cloning the gene library in an expression vector that can be replicated, transforming a suitable cell with the resulting vector database, and expressing the combinatorial genes under conditions where the desired activity facilitates isolation of the vector encoding the detected product. Recursive ensemble mutagenesis (REM) is a technique for increasing the frequency of functional mutants in a database and can be used in combination with screening assays to identify homologs.

[0800] The examples provided herein provide orthologs and paralogs of the polypeptides disclosed herein, as well as methods for identifying and isolating such orthologs and paralogs. Definitions of the terms "ortholog" and "paralog" are given below and apply to amino acid and nucleic acid sequences.

[0801] The polypeptides of the present invention include all active forms of the enzymes of the present invention, including active subsequences, such as catalytic domains or active sites. In one aspect, the present invention provides the catalytic domains or active sites set forth below. In one aspect, the present invention provides a peptide or polypeptide that comprises or consists of an active site domain that is predicted using a database such as Pfam (http: / / pfam.wustl.edu / hmmsearch.shtml), which is a large collection of multiple sequence alignments and hidden Markov models covering many common protein families, The Pfam protein families database, A. Bateman, E. Birney, L. Cerruti, R. Durbin, L. Etwiller, S. R. Eddy, S. Griffiths-Jones, K. L. Howe, M. Marshall and E. L. L. Sonnhammer, Nucleic Acids Research, 30(1):276-280, 2002) or equivalents such as the InterPro and SMART databases (http: / / www.ebi.ac.uk / interpro / scan.html, http: / / smart.embl-heidelberg.de / ).

[0802] The invention also encompasses "polypeptide variants" having the desired activity, wherein the variant polypeptide is selected from amino acid sequences having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to a specific (in particular, native) amino acid sequence represented by a specific SEQ ID NO, and containing at least one substitution modification relative to said SEQ ID NO.

[0803] 2. Nucleic Acids and Constructs

[0804] 2.1 Nucleic Acids

[0805] In this context, the following definitions apply:

[0806] The terms "nucleic acid sequence", "nucleic acid", "nucleic acid molecule" and "polynucleotide" are used interchangeably and mean a nucleotide sequence. A nucleic acid sequence can be single-stranded or double-stranded deoxyribonucleotide, or ribonucleotide of any length, and includes genes, exons, introns, sense and antisense complementary sequences, genomic DNA, cDNA, miRNA, siRNA, mRNA, rRNA, tRNA, recombinant nucleic acid sequences, isolated and purified naturally occurring DNA and / or RNA sequences, synthetic DNA and RNA sequences, fragments, primers and nucleic acid probes, both coding and non-coding sequences. As is known to those skilled in the art, the nucleic acid sequence of RNA is the same as the DNA sequence, with the difference that thymine (T) is replaced by uracil (U). The term "nucleotide sequence" should also be understood to include polynucleotide molecules or oligonucleotide molecules in the form of separate fragments or as components of larger nucleic acids.

[0807] "Isolated nucleic acid" or "isolated nucleic acid sequence" refers to a nucleic acid or nucleic acid sequence that is in an environment different from that in which it naturally occurs, and can include those that are substantially free of contaminating endogenous substances.

[0808] As used herein, the term "naturally occurring" when applied to nucleic acids refers to nucleic acids that occur in the cells of organisms in nature and have not been deliberately modified by humans in the laboratory.

[0809] A "fragment" of a polynucleotide or nucleic acid sequence refers to a contiguous nucleotide of the polynucleotides of the embodiments herein that particularly has a length of at least 15 bp, at least 30 bp, at least 40 bp, at least 50 bp, and / or at least 60 bp. In particular, a fragment of a polynucleotide comprises at least 25, more particularly at least 50, more particularly at least 75, more particularly at least 100, more particularly at least 150, more particularly at least 200, more particularly at least 300, more particularly at least 400, more particularly at least 500, more particularly at least 600, more particularly at least 700, more particularly at least 800, more particularly at least 900, more particularly at least 1000 contiguous nucleotides of the polynucleotides of the embodiments herein. Without limitation, fragments of the polynucleotides herein can be used as PCR primers, and / or as probes, or for antisense gene silencing or RNAi.

[0810] As used herein, the term "hybridizes" or hybridizes under certain conditions is intended to describe the conditions of hybridization and washing under which nucleotide sequences that are significantly identical or homologous to each other remain bound to each other. These conditions can be conditions such that sequences having at least about 70%, such as at least about 80% and such as at least about 85%, 90% or 95% identity remain bound to each other. Definitions of low stringency, medium stringency, and high stringency hybridization conditions are provided below. Appropriate hybridization conditions can also be selected by those skilled in the art with a minimum of experimentation, as exemplified by Ausubel et al. (1995, Current Protocols in Molecular Biology, John Wiley & Sons, Sections 2, 4, and 6). Additionally, stringent conditions are described in Sambrook et al. (1989, Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Press, Chapters 7, 9, and 11).

[0811] A "recombinant nucleic acid sequence" is a nucleic acid sequence obtained by bringing together genetic material from more than one source using laboratory methods (e.g., molecular cloning), thereby producing or modifying a nucleic acid sequence that is not naturally occurring and would not otherwise exist in an organism.

[0812] "Recombinant DNA technology" refers to molecular biological procedures for preparing recombinant nucleic acid sequences, such as those described, for example, in Laboratory Manuals, edited by Weigel and Glazebrook, 2002, Cold Spring Harbor Lab Press; and Sambrook et al., 1989, Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press.

[0813] The term "gene" means a DNA sequence operably linked to a suitable regulatory region (e.g., a promoter), which DNA sequence contains a region that is transcribed into an RNA molecule (e.g., mRNA in a cell). Thus, a gene can contain several operably linked sequences, such as a promoter, a 5' leader sequence (containing, for example, sequences involved in translation initiation), a coding region of cDNA or genomic DNA, introns, exons, and / or a 3' untranslated sequence containing, for example, a transcription termination site.

[0814] "Polycistronic" refers to a nucleic acid molecule that can encode more than one polypeptide separately in the same nucleic acid molecule, particularly an mRNA

[0815] A "chimeric gene" is any gene that does not normally exist in a species in nature, particularly a gene in which one or more portions of the nucleic acid sequences present are not related to each other in nature. For example, a promoter is not associated in nature with a portion or all of a transcription region or another regulatory region. The term "chimeric gene" is understood to include expression constructs in which a promoter or transcriptional regulatory sequence is operably linked to one or more coding sequences or antisense sequences (i.e., the reverse complement sequence of the sense strand) or inverted repeat sequences (sense and antisense, whereby the RNA transcript forms double-stranded RNA upon transcription). The term "chimeric gene" also includes genes obtained by combining portions of one or more coding sequences to produce a new gene.

[0816] "3' UTR" or "3' untranslated sequence" (also referred to as "3' untranslated region" or "3' end") refers to a nucleic acid sequence that exists downstream of the coding sequence of a gene and, for example, contains a transcription termination site and (in most but not all eukaryotic mRNAs) a polyadenylation signal, such as AAUAAA or a variant thereof. After transcription termination, the mRNA transcript can be cleaved downstream of the polyadenylation signal, and a poly(A) tail can be added, which poly(A) tail is involved in transporting the mRNA to the translation site (e.g., the cytoplasm).

[0817] The term "primer" refers to a short nucleic acid sequence that hybridizes to a template nucleic acid sequence and is used for the polymerization of a nucleic acid sequence complementary to the template.

[0818] The term "selectable marker" refers to any gene that can be used to select one or more cells containing the selectable marker upon expression. Examples of selectable markers are described below. Those skilled in the art will know that different antibiotic, fungicide, auxotrophic or herbicide selectable markers are applicable to different target species.

[0819] The present invention also relates to nucleic acid sequences encoding polypeptides as defined herein.

[0820] In particular, the present invention also relates to nucleic acid sequences (single-stranded and double-stranded DNA and RNA sequences, such as cDNA, genomic DNA and mRNA) encoding one of the above polypeptides and their functional equivalents, which can be obtained, for example, using artificial nucleotide analogues.

[0821] The present invention relates to isolated nucleic acid molecules encoding a polypeptide according to the present invention or a bioactive segment thereof, and to nucleic acid fragments that can be used, for example, as hybridization probes or primers for identifying or amplifying the encoding nucleic acids according to the present invention.

[0822] The present invention also relates to nucleic acids having a certain degree of "identity" with the sequences specifically disclosed herein. "Identity" between two nucleic acids means nucleotide identity over the entire length of the nucleic acid in each case.

[0823] "Identity" between two nucleotide sequences (similarly applicable to peptide or amino acid sequences) is a function of the number of identical nucleotide residues (or amino acid residues) in the two sequences when the two sequences are aligned. Identical residues are defined as the same residues in the two sequences at a given position in the alignment. As used herein, the percent sequence identity is calculated by taking the number of identical residues between the two sequences, dividing by the total number of residues in the shortest sequence, and multiplying by 100 from the best alignment. The best alignment is the alignment for which the percent identity is the highest possible value. Gaps may be introduced into one or both of the sequences at one or more positions in the alignment to obtain the best alignment. These gaps are then considered non-identical residues for calculating the percent sequence identity. Alignment for the purpose of determining the percent amino acid or nucleic acid sequence identity can be achieved in various ways using computer programs and publicly available computer programs, for example, available on the World Wide Web.

[0824] In particular, the BLAST program (Tatiana et al., FEMS Microbiol Lett. [FEMS Microbiology Letters], 1999, 174:247-250, 1999) set as the default parameter is available from the website of the National Center for Biotechnology Information (NCBI) at ncbi.nlm.nih.gov / BLAST / bl2seq / wblast2.cgi and can be used to obtain the optimal alignment of protein or nucleic acid sequences and calculate the percentage of sequence identity.

[0825] In another example, identity can be calculated using the Vector NTISuite 7.1 program from Informax (USA), the Clustal method (Higgins DG, Sharp PM. ((1989))) and the following settings:

[0826] Multiple sequence alignment parameters:

[0827]

[0828] Pairwise sequence alignment parameters:

[0829]

[0830] Alternatively, identity can be determined according to Chenna et al. (2003), web page: http: / / www.ebi.ac.uk / Tools / clustalw / index.html# and the following settings

[0831]

[0832]

[0833] All nucleic acid sequences (single-stranded and double-stranded DNA and RNA sequences, such as cDNA and mRNA) mentioned herein can be generated from nucleotide building blocks by chemical synthesis in a known manner, for example, by condensation of fragments of single overlapping complementary nucleic acid building blocks of a double helix. Chemical synthesis of oligonucleotides can be carried out, for example, in a known manner by the phosphoramidite method (Voet, Voet, 2nd edition, Wiley Press [Wiley Press], New York, pp. 896-897). The accumulation of synthetic oligonucleotides and the filling of gaps by the Klenow fragment of DNA polymerase and ligation reactions and general cloning techniques are described in Sambrook et al. (1989), see below.

[0834] In addition, the nucleic acid molecules according to the invention may also contain untranslated sequences from the 3' and / or 5' ends of the coding genetic regions.

[0835] The present invention further relates to nucleic acid molecules that are complementary to the specifically described nucleotide sequences or segments thereof.

[0836] The nucleotide sequences according to the invention enable the production of probes and primers that can be used to identify and / or clone homologous sequences in other cell types and organisms. Such probes or primers typically comprise a nucleotide sequence region that hybridizes under "stringent" conditions (as defined elsewhere herein) to at least about 12, particularly at least about 25, for example about 40, 50 or 75 consecutive nucleotides of the sense strand or the corresponding antisense strand of the nucleic acid sequence according to the invention.

[0837] "Homologous" sequences include orthologous or paralogous sequences. Methods for identifying orthologs or paralogs (including phylogenetic methods, sequence similarity and hybridization methods) are known in the art and are described herein.

[0838] "Paralogs" are produced by gene duplication, which results in two or more genes with similar sequences and similar functions. Paralogs typically cluster together and are formed by gene duplication within related plant species. Paralogs are found in groups of similar genes using pairwise Blast analysis or programs such as CLUSTAL during phylogenetic analysis of gene families. Among paralogs, consensus sequences can be identified as sequences that are unique within related genes and have similar gene functions.

[0839] "Orthologs" or orthologous sequences are sequences that are similar to each other because they exist in species that have descended from a common ancestor. For example, plant species known to have a common ancestor contain many enzymes with similar sequences and functions. A person skilled in the art can identify orthologous sequences and predict the functions of orthologs, for example, by constructing a multigene tree of a gene family of a species using programs such as CLUSTAL or BLAST. One method for identifying or confirming similar functions between homologous sequences is by comparing the transcript profiles in host cells or organisms (such as plants or microorganisms) overexpressing or lacking (knockout / knockdown) the relevant polypeptide. A person skilled in the art will understand that genes with similar transcript profiles (sharing more than 50% of the regulated transcripts, or sharing more than 70% of the regulated transcripts, or sharing more than 90% of the regulated transcripts) will have similar functions. It is expected that homologs, paralogs, orthologs and any other variants of the sequences herein will act in a similar manner by preparing host cells, organisms (such as plants or microorganisms) that produce the enzymes of the present invention.

[0840] The term "selectable marker" refers to any gene that can be used to select one or more cells containing the selectable marker upon expression. Examples of selectable markers are described below. Those skilled in the art will know that different antibiotic, fungicide, auxotrophic or herbicide selectable markers are suitable for different target species.

[0841] The nucleic acid molecules according to the invention can be retrieved by standard techniques of molecular biology and according to the sequence information provided by the invention. For example, one of the specifically disclosed complete sequences or a segment thereof can be used as a hybridization probe and standard hybridization techniques (such as those described in Sambrook, (1989)) to isolate cDNA from a suitable cDNA library.

[0842] In addition, nucleic acid molecules containing one of the disclosed sequences or a segment thereof can be isolated by polymerase chain reaction using oligonucleotide primers constructed based on this sequence. The nucleic acid amplified in this way can be cloned into a suitable vector and characterized by DNA sequencing. The oligonucleotides according to the invention can also be produced by standard synthetic methods, for example using an automated DNA synthesizer.

[0843] The nucleic acid sequences according to the invention or their derivatives, homologs or parts of these sequences can be isolated from other bacteria, for example, by conventional hybridization techniques or PCR techniques via genomic or cDNA libraries. These DNA sequences hybridize with the sequences according to the invention under standard conditions.

[0844] "Hybridization" means the ability of a polynucleotide or oligonucleotide to bind to a nearly complementary sequence under standard conditions, and non-specific binding does not occur between non-complementary partners under these conditions. For this purpose, the sequences can be 90%-100% complementary. The property that complementary sequences can specifically bind to each other is used, for example, in RNA blotting or DNA blotting or in primer binding in PCR or RT-PCR.

[0845] Short oligonucleotides of conserved regions are advantageously used for hybridization. However, longer fragments or the complete sequences of the nucleic acids according to the invention can also be used for hybridization. These "standard conditions" vary depending on the nucleic acid used (oligonucleotide, longer fragment or complete sequence) or depending on which type of nucleic acid (DNA or RNA) is used for hybridization. For example, the melting temperature of a DNA:DNA hybrid is approximately 10°C lower than that of a DNA:RNA hybrid of the same length.

[0846] For example, depending on the particular nucleic acid, standard conditions mean a temperature between 42°C and 58°C in an aqueous buffer solution having a concentration between 0.1 and 5x SSC (1X SSC = 0.15 M NaCl, 15 mM sodium citrate, pH 7.2) or alternatively in the presence of 50% formamide (e.g., 42°C, in 5x SSC, 50% formamide). Advantageously, the hybridization conditions for a DNA:DNA hybrid are 0.1x SSC and a temperature between about 20°C and 45°C, particularly between about 30°C and 45°C. For a DNA:RNA hybrid, the hybridization conditions are advantageously 0.1x SSC and a temperature between about 30°C and 55°C, particularly between about 45°C and 55°C. These stated hybridization temperatures are examples of melting temperature values calculated for nucleic acids having a length of approximately 100 nucleotides and a G+C content of 50% in the absence of formamide. The experimental conditions for DNA hybridization are described in relevant genetics textbooks, e.g., Sambrook et al., 1989, and formulas known to those skilled in the art, e.g., based on the length of the nucleic acid, the type of hybrid, or the G+C content, can be used to calculate them. Those skilled in the art can obtain additional information on hybridization from the following textbooks: Ausubel et al. (eds.), (1985), Brown (ed.) (1991).

[0847] "Hybridization" can in particular be carried out under stringent conditions. Such hybridization conditions are described, for example, in Sambrook (1989) or Current Protocols in Molecular Biology, John Wiley & Sons, New York (1989), 6.3.1-6.3.6.

[0848] As used herein, the terms hybridization or hybridizing under certain conditions are intended to describe the conditions of hybridization and washing under which nucleotide sequences that are substantially identical or homologous to each other remain bound to each other. These conditions can be conditions such that sequences having at least about 70%, such as at least about 80% and such as at least about 85%, 90% or 95% identity remain bound to each other. Definitions of low stringency, medium stringency and high stringency hybridization conditions are provided herein.

[0849] Suitable hybridization conditions can be selected by those skilled in the art with a minimum of experimentation, as exemplified by Ausubel et al. (1995, Current Protocols in Molecular Biology, John Wiley & Sons, Sections 2, 4, and 6). Additionally, stringent conditions are described in Sambrook et al. (1989, Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Press, Chapters 7, 9, and 11).

[0850] As used herein, the defined conditions of low stringency are as follows. Filters containing DNA are pre-treated for 6 h at 40 °C in a solution containing 35% formamide, 5x SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.1% PVP, 0.1% Ficoll, 1% BSA, and 500 μg / ml denatured salmon sperm DNA. Hybridization is carried out in the same solution with the following modifications: 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg / ml salmon sperm DNA, 10% (wt / vol) dextran sulfate, and 5 - 20 x 106 32P-labelled probes are used. The filters are incubated in the hybridization mixture at 40 °C for 18 - 20 h and then washed at 55 °C for 1.5 h. In a solution containing 2x SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS. The wash solution is replaced with fresh solution and incubation is continued at 60 °C for 1.5 h. The filters are blotted dry and exposed for autoradiography.

[0851] As used herein, the conditions for medium stringency are as follows. A filter containing DNA is pre-treated for 7 h at 50 °C in a solution containing 35% formamide, 5x SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.1% PVP, 0.1% Ficoll, 1% BSA and 500 μg / ml denatured salmon sperm DNA. Hybridization is carried out in the same solution with the following modifications: 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg / ml salmon sperm DNA, 10% (wt / vol) dextran sulfate and 5 - 20 x 106 32P-labelled probes are used. The filter is incubated in the hybridization mixture at 50 °C for 30 h and then washed at 55 °C for 1.5 h. In a solution containing 2x SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA and 0.1% SDS. The wash solution is replaced with fresh solution and incubation is continued at 60 °C for 1.5 h. The filter is blotted dry and exposed for autoradiography.

[0852] As used herein, the conditions for high stringency are as follows. A filter containing DNA is pre-hybridized at 65 °C for 8 h to overnight in a buffer consisting of 6x SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA and 500 μg / ml denatured salmon sperm DNA. The filter is hybridized at 65 °C for 48 h in a pre-hybridization mixture containing 100 μg / ml denatured salmon sperm DNA and 5 - 20 x 106 cpm of 32P-labelled probe. The filter is washed at 37 °C for 1 h in a solution containing 2x SSC, 0.01% PVP, 0.01% Ficoll and 0.01% BSA. Subsequently, it is washed in 0.1x SSC at 50 °C for 45 minutes.

[0853] If the above conditions are not appropriate (e.g., as used for cross-species hybridization), other low, medium and high stringency conditions well known in the art may be used (e.g., as used for cross-species hybridization).

[0854] A detection kit for the nucleic acid sequence encoding the polypeptide of the present invention may include primers and / or probes specific for the nucleic acid sequence encoding the polypeptide, and related protocols for using these primers and / or probes to detect the nucleic acid sequence encoding the polypeptide in a sample. Such a detection kit can be used to determine whether a plant, organism, microorganism or cell has been modified, i.e., transformed with the sequence encoding the polypeptide.

[0855] To test the function of variant DNA sequences according to the embodiments herein, the sequence of interest is operably linked to a selectable or screenable marker gene and the expression of the reporter gene is tested in a transient expression assay, for example, with microorganisms or with protoplasts or in stably transformed plants.

[0856] The invention also relates to derivatives of the specifically disclosed or derivable nucleic acid sequences.

[0857] Thus, additional nucleic acid sequences according to the invention can be derived from the sequences specifically disclosed herein and can differ therefrom by one or more, such as 1 to 20, especially 1 to 15 or 5 to 10 additions, substitutions, insertions or deletions of one or several (e.g., such as 1 to 10) nucleotides and moreover encode polypeptides having the desired property profile.

[0858] The invention also encompasses nucleic acid sequences that contain so-called silent mutations or have been altered according to the codon usage of a particular original or host organism compared to the specifically stated sequences.

[0859] According to a particular embodiment of the invention, variant nucleic acids can be prepared so that their nucleotide sequences are adapted to a particular expression system. For example, if an amino acid is encoded by a particular codon, it is known that bacterial expression systems express polypeptides more efficiently. Due to the degeneracy of the genetic code, more than one codon can encode the same amino acid sequence, and multiple nucleic acid sequences can encode the same protein or polypeptide, all of these DNA sequences being encompassed by the embodiments herein. Where appropriate, the nucleic acid sequences encoding the polypeptides described herein can be optimized for increased expression in a host cell. For example, the nucleic acids of the embodiments herein can be synthesized using host-specific codons to improve expression.

[0860] The invention also encompasses naturally occurring variants of the sequences described therein, such as splice variants or allelic variants.

[0861] Allelic variants can have at least 60% homology at the derived amino acid level, especially at least 80% homology over the entire sequence range, very especially at least 90% homology (with respect to homology at the amino acid level, reference should be made to the details given above for polypeptides). Advantageously, the homology can be higher in partial regions of the sequence.

[0862] The invention also relates to sequences that can be obtained by conservative nucleotide substitutions (i.e., as a result, the amino acid in question is replaced by an amino acid having the same charge, size, polarity and / or solubility).

[0863] The present invention also relates to molecules derived from specifically disclosed nucleic acids by sequence polymorphisms. Due to natural allelic variations, such genetic polymorphisms may exist in cells from different populations or within a population. Allelic variants may also include functional equivalents. These natural variations typically result in 1% to 5% variation in the nucleotide sequence of the gene. The polymorphisms may lead to changes in the amino acid sequence of the polypeptides disclosed herein. Allelic variants may also include functional equivalents.

[0864] In addition, derivatives should also be understood as homologues of the nucleic acid sequences according to the invention, such as animal, plant, fungal or bacterial homologues, shortened sequences, single-stranded DNA or RNA of coding and non-coding DNA sequences. For example, homologues have at least 40%, particularly at least 60%, especially particularly at least 70%, very particularly at least 80% homology over the entire DNA region given in the sequences specifically disclosed herein at the DNA level.

[0865] In addition, derivatives should be understood as, for example, fusions with promoters. The promoter added to the stated nucleotide sequence may be modified by at least one nucleotide exchange, at least one insertion, inversion and / or deletion, but without impairing the functionality or efficacy of the promoter. In addition, the efficacy of the promoter may be increased by altering its sequence, or it may be completely exchanged with a more effective promoter of an organism even from a different genus.

[0866] 2.2 Constructs for expressing the polypeptides of the present invention

[0867] In this context, the following definitions apply:

[0868] "Gene expression" encompasses "heterologous expression" and "overexpression" and relates to gene transcription and mRNA translation into protein. Overexpression refers to the production of a gene product, as measured by the level of mRNA, polypeptide and / or enzyme activity in transgenic cells or organisms, which exceeds the production level in non-transformed cells or organisms with a similar genetic background.

[0869] As used herein, an "expression vector" means a nucleic acid molecule engineered using molecular biology methods and recombinant DNA techniques for delivering foreign or exogenous DNA into a host cell. An expression vector typically includes the sequences required for proper transcription of a nucleotide sequence. The coding region usually encodes a protein of interest, but may also encode RNA (e.g., antisense RNA, siRNA, etc.).

[0870] As used herein, "expression vector" includes any linear or circular recombinant vector, including but not limited to viral vectors, phages, and plasmids. One skilled in the art can select a suitable vector according to the expression system. In one embodiment, the expression vector includes the nucleic acid of the embodiments herein, which is operably linked to at least one "regulatory sequence" (such as a transcriptional promoter, operon, or enhancer) that controls transcription, translation, initiation, and termination, or an mRNA ribosome binding site, and optionally includes at least one selectable marker. A nucleotide sequence is "operably linked" when the regulatory sequence is functionally related to the nucleic acid of the embodiments herein.

[0871] As used herein, "expression system" encompasses any combination of nucleic acid molecules required for expressing one polypeptide or co-expressing two or more polypeptides in vivo or in vitro in a given expression host. The corresponding coding sequences can be located on a single nucleic acid molecule or vector (e.g., a vector containing multiple cloning sites), or on a polycistronic nucleic acid, or can be distributed on two or more physically distinct vectors. As a particular example, mention may be made of an operon comprising a promoter sequence, one or more operon sequences, and one or more structural genes each encoding an enzyme as described herein.

[0872] As used herein, the terms "amplifying" and "amplification" refer to generating or detecting a recombinant of a naturally expressed nucleic acid using any suitable amplification method, as described in detail below. For example, the present invention provides methods and reagents (e.g., specific degenerate oligonucleotide primer pairs, oligo dT primers) for amplifying (e.g., by polymerase chain reaction, PCR) the naturally expressed (e.g., genomic DNA or mRNA) or recombinant (e.g., cDNA) nucleic acids of the present invention in vivo, ex vivo, or in vitro.

[0873] "Regulatory sequence" refers to a nucleic acid sequence that determines the expression level of the nucleic acid sequence of the embodiments herein and is capable of regulating the transcription rate of the nucleic acid sequence operably linked to the regulatory sequence. Regulatory sequences include promoters, enhancers, transcription factors, promoter elements, etc.

[0874] According to the present invention, a "promoter", "nucleic acid having promoter activity" or "promoter sequence" is understood to mean a nucleic acid that regulates the transcription of a nucleic acid when functionally associated with the nucleic acid to be transcribed. A "promoter" particularly refers to a nucleic acid sequence that controls the expression of a coding sequence by providing binding sites for RNA polymerase and other factors required for correct transcription (including but not limited to transcription factor binding sites, repressor and activator protein binding sites). The meaning of the term promoter also includes the term "promoter regulatory sequence". Promoter regulatory sequences can include upstream and downstream elements that can affect the transcription, RNA processing or stability of the associated coding nucleic acid sequence. Promoters include naturally derived sequences and synthetic sequences. Relative to the direction of transcription starting at the transcription start site, the coding nucleic acid sequence is generally located downstream of the promoter.

[0875] In this context, a "functional" or "operational" linkage is understood to mean, for example, the sequential arrangement of one of the nucleic acids with a regulatory sequence. For example, a sequence having promoter activity and a nucleic acid sequence to be transcribed and optionally additional regulatory elements (such as nucleic acid sequences that ensure the transcription of the nucleic acid and, for example, terminators) are linked in such a way that each regulatory element can perform its function during the transcription of the nucleic acid sequence. This does not necessarily require a direct linkage in the chemical sense. Genetic control sequences (such as enhancer sequences) can even exert their function on the target sequence from more distant positions or even from positions distant from other DNA molecules. A preferred arrangement is one in which the nucleic acid sequence to be transcribed is located behind the promoter sequence (i.e., at the 3' end of the promoter sequence) such that the two sequences are covalently linked together. The distance between the promoter sequence and the nucleic acid sequence to be recombinantly expressed can be less than 200 base pairs, or less than 100 base pairs, or less than 50 base pairs.

[0876] In addition to promoters and terminators, the following can be mentioned as examples of other regulatory elements: targeting sequences, enhancers, polyadenylation signals, selectable markers, amplification signals, origins of replication, etc. Suitable regulatory sequences are described, for example, in Goeddel, Gene Expression Technology: Methods in Enzymology [Gene Expression Technology: Methods in Enzymology] 185, Academic Press, San Diego, CA [Academic Press, San Diego, California] (1990).

[0877] The term "constitutive promoter" refers to an unregulated promoter that permits continuous transcription of a nucleic acid sequence operably linked thereto.

[0878] As used herein, the term "operably linked" refers to a linkage of polynucleotide elements in a functional relationship. A nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, if a promoter (or more precisely, a transcriptional regulatory sequence) affects the transcription of a coding sequence, the promoter is operably linked to the coding sequence. Operably linked means that the DNA sequences being linked are typically contiguous. The nucleotide sequence associated with the promoter sequence may have a homologous origin or a heterologous origin relative to the plant to be transformed. The sequence may also be entirely synthetic or partially synthetic. Regardless of its origin, the nucleic acid sequence associated with the promoter sequence will be expressed or silenced according to the properties of the promoter to which it is linked after binding to the polypeptides of the examples herein. The relevant nucleic acid may encode a protein that is desired to be expressed or inhibited throughout the organism at all times or alternatively at a specific time or in a specific tissue, cell, or cell compartment. Such nucleotide sequences particularly encode proteins that confer the desired phenotypic traits to the host cell or the organism that is altered or transformed therewith. More particularly, the associated nucleotide sequence results in the production of one or more products of interest as defined herein in the cell or organism. In particular, the nucleotide sequence encodes a polypeptide having an enzyme activity as defined herein.

[0879] The nucleotide sequence as described hereinabove may be part of an "expression cassette". The terms "expression cassette" and "expression construct" are used synonymously. The (especially recombinant) expression construct contains a nucleotide sequence that encodes a polypeptide according to the invention and is under the genetic control of regulatory nucleic acid sequences.

[0880] In the methods applied according to the invention, the expression cassette may be part of an "expression vector", especially part of a recombinant expression vector.

[0881] According to the invention, an "expression unit" is understood to mean a nucleic acid having expression activity, which contains a promoter as defined herein and regulates the expression (i.e., transcription and translation) of the nucleic acid or the gene after being functionally linked to the nucleic acid or the gene to be expressed. Thus, in this regard, it is also referred to as a "regulatory nucleic acid sequence". In addition to the promoter, other regulatory elements, such as enhancers, may also be present.

[0882] According to the invention, an "expression cassette" or "expression construct" is to be understood as meaning an expression unit that is functionally linked to the nucleic acid or the gene to be expressed. Compared to the expression unit, the expression cassette thus contains not only the nucleic acid sequences that regulate transcription and translation, but also the nucleic acid sequence that is to be expressed as a protein as a result of transcription and translation.

[0883] In the context of the present invention, the terms "expression" or "overexpression" describe the generation or increase of the intracellular activity of one or more polypeptides encoded by the corresponding DNA in a microorganism. For this purpose, it is possible, for example, to introduce a gene into an organism, replace an existing gene with another gene, increase the copy number of one or more genes, use a strong promoter or use a gene encoding the corresponding polypeptide with high activity; optionally, these measures can be combined.

[0884] In particular, such constructs according to the invention comprise a promoter upstream of the 5'-end of the corresponding coding sequence and a terminator sequence downstream of the 3'-end and optionally other customary regulatory elements, each operably linked to the coding sequence.

[0885] The nucleic acid constructs according to the invention in particular comprise a sequence encoding a polypeptide which is, for example, derived from the amino acid-related SEQ ID NO as described therein or its reverse complement sequence, or derivatives and homologues thereof, and which has been operably or functionally linked to one or more regulatory signals, advantageously for controlling (e.g., increasing) gene expression.

[0886] In addition to these regulatory sequences, the natural regulation of these sequences may still be present before the actual structural gene and may optionally have been genetically modified such that the natural regulation has been switched off and the expression of the gene has been enhanced. However, the nucleic acid construct can also have a simpler construction, i.e., no additional regulatory signals are inserted before the coding sequence and the natural promoter and its regulation are not removed. Instead, the natural regulatory sequences are mutated such that regulation no longer occurs and gene expression increases.

[0887] Preferred nucleic acid constructs also advantageously comprise one or more of the already mentioned "enhancer" sequences functionally linked to the promoter, which sequences enable enhanced expression of the nucleic acid sequence. Additional advantageous sequences can also be inserted at the 3'-end of the DNA sequence, such as additional regulatory elements or terminators. One or more copies of the nucleic acid according to the invention can be present in the construct. In the construct, other markers can also optionally be present, such as genes complementing auxotrophy or antibiotic resistance, in order to select the construct.

[0888] Examples of suitable regulatory sequences are present in promoters such as cos, tac, trp, tet, trp-tet, lpp, lac, lpp-lac, lacI q 、T7、T5、T3、gal、trc、ara、rhaP(rhaP BAD )SP6、lambda-P R or lambda-P LPromoters, and these are advantageously used in Gram-negative bacteria. Additional advantageous regulatory sequences are present, for example, in the Gram-positive promoters amy and SPO2, and in the yeast or fungal promoters ADC1, MFalpha, AC, P-60, CYC1, GAPDH, TEF, rp28, ADH. Artificial promoters can also be used for regulation.

[0889] For expression in a host organism, the nucleic acid construct is advantageously inserted into a vector (such as a plasmid or a phage), which enables optimal expression of the gene in the host. In addition to plasmids and phages, vectors are also understood to mean all other vectors known to the person skilled in the art, namely, for example, viruses (such as SV40, CMV, baculovirus, and adenovirus), transposons, IS elements, plasmids, cosmids, and linear or circular DNA or artificial chromosomes. These vectors are capable of autonomous replication or chromosomal replication in the host organism. These vectors are a further development of the present invention. Binary vectors or cpo-integration vectors are also suitable.

[0890] Suitable plasmids are, for example, in Escherichia coli pLG338, pACYC184, pBR322, pUC18, pUC19, pKC30, pRep4, pHS1, pKK223-3, pDHE19.2, pHS2, pPLc236, pMBL24, pLG200, pUR290, pIN-III 113 -B1, λgt11 or pBdCI, in Streptomyces pIJ101, pIJ364, pIJ702 or pIJ361, in Bacillus pUB110, pC194 or pBD214, in Corynebacterium pSA77 or pAJ667, in fungi pALS1, pIL2 or pBB116, in yeast 2alphaM, pAG-1, YEp6, YEp13 or pEMBLYe23, or in plants pLGV23, pGHlac + , pBIN19, pAK2004 or pDH51. The plasmids mentioned above are a small set of possible plasmids. Additional plasmids are well known to the person skilled in the art and can be found, for example, in the book Cloning Vectors (edited by Pouwels P.H. et al., Elsevier, Amsterdam - New York - Oxford, 1985, ISBN 0 444 904018).

[0891] In a further development of the vector, the vector comprising the nucleic acid construct according to the invention or the nucleic acid according to the invention can also advantageously be introduced into a microorganism in the form of linear DNA and integrated into the genome of the host organism via heterologous or homologous recombination. Such linear DNA can consist of a linearized vector such as a plasmid or only of the nucleic acid construct or nucleic acid according to the invention.

[0892] For optimal expression of a heterologous gene in an organism, it is advantageous to modify the nucleic acid sequence to match the specific "codon usage" employed in the organism. The "codon usage" can be readily determined by computer evaluation of other known genes of the organism in question.

[0893] The expression cassette according to the invention is generated by fusing a suitable promoter with a suitable coding nucleotide sequence and a terminator or polyadenylation signal. Conventional recombinant and cloning techniques are used for this purpose, as described, for example, in: T. Maniatis, E. F. Fritsch and J. Sambrook, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1989) and T. J. Silhavy, M. L. Berman and L. W. Enquist, Experiments with Gene Fusions, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1984) and Ausubel, F. M. et al., Current Protocols in Molecular Biology, Greene Publishing Assoc. and Wiley Interscience (1987).

[0894] For expression in a suitable host organism, the recombinant nucleic acid construct or gene construct is advantageously inserted into a host-specific vector, which enables optimal expression of the gene in the host. Vectors are well known to the person skilled in the art and can be found, for example, in "cloning vectors" (edited by Pouwels P. H. et al., Elsevier, Amsterdam - New York - Oxford, 1985).

[0895] Alternative embodiments of the examples herein provide methods for "altering gene expression" in a host cell. For example, the polynucleotides of the examples herein can be enhanced, overexpressed, or induced in a host cell or host organism under certain contexts (e.g., when exposed to certain temperatures or culture conditions).

[0896] Altering the expression of the polynucleotides provided herein can also result in ectopic expression, which is a different expression pattern in the altered organism and in a control or wild-type organism. The expression alteration occurs due to the interaction of the polypeptides of the examples herein with exogenous or endogenous regulators, or due to chemical modification of the polypeptides. The term also refers to an altered expression pattern of the polynucleotides of the examples herein that alters or completely suppresses activity when below the detection level.

[0897] In one embodiment, the present disclosure also provides an isolated, recombinant, or synthetic polynucleotide encoding a polypeptide or variant polypeptide provided herein.

[0898] In one embodiment, several nucleic acid sequences encoding polypeptides are co-expressed in a single host, particularly under the control of different promoters. In another embodiment, several nucleic acid sequences encoding polypeptides can be present on a single transformation vector, or co-transformed simultaneously using separate vectors and transformants containing both chimeric genes are selected. Similarly, one or more genes encoding polypeptides can be expressed in a single plant, cell, microorganism, or organism together with other chimeric genes.

[0899] Experimental Section

[0900] Examples

[0901] A. Synthesis

[0902] 1. Preparation of Compound I.a

[0903]

[0904] 1.1 Preparation of 4-[6-(difluoromethyl)-5-methyl-3-pyridinyl]spiro[1,3-benzoxazine-2,1'-cyclobutane] (Exemplary Compound 25 in Table I)

[0905] 1.1a) Preparation of spiro[3H-1,3-benzoxazine-2,1'-cyclobutane]-4-one p-Toluenesulfonic acid (98 mg, 0.2 eq) was added to a suspension of 3-fluoro-2-hydroxy-benzamide (400 mg, 1 eq) and cyclobutanone (542 mg, 3 eq) in toluene (30 ml), and the mixture was heated under reflux to remove water azeotropically for 12 h. The reaction solution was cooled and concentrated in vacuo, and the resulting residue was diluted with ethyl acetate, washed successively with 2N HCl, water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give the title compound (526 mg) as a brown powder.

[0906] 1 H NMR(400MHz,CDCl 3 ):δ[ppm]:8.02-7.86(m,1H),7.47(ddd,J=8.3,7.3,1.7Hz,1H),7.10(td,J=7.5,1.1Hz,1H),7.01(ddd,J=8.3,1.1,0.5Hz,1H),6.62(s,1H),2.65-2.50(m,2H),2.34(ddtt,J=12.5,6.4,3.1,1.5Hz,2H),2.07-1.91(m,1H),1.84(dtt,J=11.6,9.3,6.4Hz,1H).

[0907] 1.1b) Preparation of spiro[1,3-benzoxazine-2,1'-cyclobutane]-4-yl trifluoromethanesulfonate Under cooling at -78 °C, trifluoromethanesulfonic anhydride (7.8 g, 2.5 eq) and 2,6-lutidine (2.38 g, 2 eq) were added dropwise to a suspension of spiro[3H-1,3-benzoxazine-2,1'-cyclobutane]-4-one (2.1 g, 1 eq) in dichloromethane (120 mL), and the mixture was stirred at the same temperature for 1.0 h. The reaction mixture was stirred at 0 °C for 20 min, poured into ice water, and the solution was extracted with dichloromethane. The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give the title compound (1.8 g) as a brown oil. The title compound was used directly without further purification.

[0908] 1.1c) Preparation of 4-[6-(difluoromethyl)-5-methyl-3-pyridyl]spiro[1,3-benzoxazine-2,1'-cyclobutane]

[0909] 1.1c) Preparation of 4-[6-(difluoromethyl)-5-methyl-3-pyridyl]spiro[1,3-benzoxazine-2,1'-cyclobutane]

[0910] Add [6-(difluoromethyl)-5-methyl-3-pyridyl]boronic acid (572 mg, 1.1 eq), potassium carbonate (1.54 g, 4 eq), water (2 ml) and dichlorobis(triphenylphosphine)palladium(II) (391 mg, 0.2 eq) to a solution of spiro[1,3-benzoxazine-2,1'-cyclobutane]-4-yl trifluoromethanesulfonate (900 mg, 1 eq) in dimethoxyethane (10 mL), and stir the mixture at 80 °C for 2.5 h under an argon atmosphere. After cooling, dilute the reaction solution with ethyl acetate, and wash the solution successively with water and brine, dry over anhydrous magnesium sulfate, and concentrate in vacuo. Purify the crude product by silica gel high performance liquid chromatography (HPLC - column Kinetex XB C18 1,7 μ (50×2,1 mm); eluent: acetonitrile / water (gradient from 5:95 to 100:0 in 1.5 min at 60 °C, flow rate gradient from 0.8 to 1.0 ml / min in 1.5 min)) to obtain the title compound (97 mg) as a yellowish brown oil.

[0911] 1 H NMR(400MHz,CDCl 3 ):δ[ppm]:8.67–8.60(m,1H),7.90–7.84(m,1H),7.42(td,J=7.8,1.6Hz,1H),7.12(dd,J=7.7,1.6Hz,1H),7.02(d,J=8.2Hz,1H),6.98–6.93(m,1H),6.75(t,J=54.5Hz,1H),2.59(s,3H),2.57–2.46(m,4H),1.99(dddd,J=25.7,15.6,7.8,4.1Hz,2H)。

[0912] The compounds listed in Table I are prepared in a similar manner.

[0913] Table I

[0914]

[0915]

[0916]

[0917]

[0918]

[0919]

[0920]

[0921]

[0922] *HPLC: High Performance Liquid Chromatography; HPLC - column Kinetex XB C18 1,7 μ (50×2,1 mm); Eluent: acetonitrile / water + 0.1% trifluoroacetic acid (gradient from 5:95 to 100:0 in 1.5 min at 60 °C, flow rate gradient from 0.8 to 1.0 ml / min in 1.5 min).

[0923] R t : Retention time in minutes.

[0924] 2. Preparation of Compound I.b

[0925]

[0926] 2.1 Preparation of 4 - [6 - (difluoromethyl) - 5 - methyl - 3 - pyridyl] - 8 - fluoro - 2,2 - dimethyl - 1H - quinazoline (Exemplary Compound 44 in Table II)

[0927] 2.1a) Preparation of 1 - [6 - (difluoromethyl) - 5 - methyl - 3 - pyridyl] - (3 - fluoro - 2 - nitro - phenyl) methanol

[0928] At - 78 °C under N 2 2, a solution of 1 - fluoro - 3 - iodo - 2 - nitrobenzene (1440 mg, 5.3 mmol) in THF (2 mL) was added dropwise with a solution of PhMgBr in THF (3 M) (1.9 mL, 5.6 mmol). The mixture was stirred at - 78 °C for 1 h. Then at - 78 °C under N 2 2, a solution of 6 - (difluoromethyl) - 5 - methyl - pyridine - 3 - carbaldehyde (600 mg, 3.5 mmol) in THF (10 mL) was added dropwise to the mixture, and the mixture was stirred at - 78 °C for 3 h. The mixture was quenched with ice - water (50 mL), and the solution was extracted with EtOAc (15 mL×3). The combined organic layers were successively washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give the title compound as a yellow solid.

[0929] 1 1H NMR (400 MHz, DMSO): δ [ppm]: 8.41 (d, J = 1.5 Hz, 1H), 7.74 - 7.65 (m, 2H), 7.60 - 7.51 (m, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.16 - 6.85 (m, 1H), 6.72 (d, J = 4.8 Hz, 1H), 6.01 (d, J = 4.6 Hz, 1H), 2.42 (s, 3H)

[0930] 2.1 b) Preparation of (2-Amino-3-fluoro-phenyl)-[6-(difluoromethyl)-5-methyl-3-pyridyl]methanol

[0931] A mixture of [6-(Difluoromethyl)-5-methyl-3-pyridyl]-(3-fluoro-2-nitro-phenyl)methanol (550 mg, 1.6 mmol) and Raney Ni (110 mg) in EtOH (10 mL) was stirred at 20 °C under H 2 (15 PSi) for 1 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was triturated with (PE:EtOAc = 10:1) to afford the title compound as a yellow solid.

[0932] 1 H NMR (400 MHz, CDCl 3 ): δ [ppm]: 8.44 (s, 1H), 7.60 (s, 1H), 7.01 (ddd, J = 1.2, 8.2, 10.7 Hz, 1H), 6.85 - 6.55 (m, 3H), 5.94 (br s, 1H), 4.15 (br s, 2H), 2.88 (br d, J = 3.5 Hz, 1H), 2.51 (s, 3H)

[0933] 2.1 c) Preparation of (2-Amino-3-fluoro-phenyl)-[6-(difluoromethyl)-5-methyl-3-pyridyl]methanone

[0934] At 20 °C, K 2 CO 3 (442 mg, 3.2 mmol) and CuCl (31 mg, 0.32 mmol) were added to a solution of (2-Amino-3-fluoro-phenyl)-[6-(difluoromethyl)-5-methyl-3-pyridyl]methanol (450 mg, 1.6 mmol) in DMF (10 mL), and the mixture was stirred at 65 °C under O 2 (15 PSi) for 16 h. The mixture was poured into ice water (30 mL) and filtered. The filtrate was extracted with EtOAc (30 mL × 3), washed with brine (15 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The crude product was purified by silica gel liquid chromatography (PE:EtOAc = 5:1) to afford the title compound as a yellow oil.

[0935] 1 H NMR (400 MHz, CDCl 3): δ [ppm]: 8.65 (s, 1H), 7.85 (s, 1H), 7.23 - 7.16 (m, 2H), 6.90 - 6.61 (m, 1H), 6.58 (dt, J = 4.9, 8.0 Hz, 1H), 6.29 (br s, 2H), 2.60 (s, 3H)

[0936] 2.1d) Preparation of 4-[6-(difluoromethyl)-5-methyl-3-pyridinyl]-8-fluoro-2,2-dimethyl-1H-quinazoline

[0937] A mixture of (2-amino-3-fluoro-phenyl)-[6-(difluoromethyl)-5-methyl-3-pyridinyl]methanone (200 mg, 0.7 mmol) and NH 4 OAc (539 mg, 7.0 mmol) in acetone (7 mL) was stirred at 65 °C for 4 h. The mixture was poured into ice water (15 mL), extracted with EtOAc (10 mL × 3), washed with brine (15 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo. The crude product was purified by silica gel liquid chromatography (PE:EtOAc = 3:1) to give the title compound as a yellow solid.

[0938] 1 1H NMR (400 MHz, CDCl 3 ): δ [ppm]: 8.55 (s, 1H), 7.77 (s, 1H), 7.08 (ddd, J = 1.1, 8.2, 10.4 Hz, 1H), 6.93 - 6.52 (m, 3H), 4.25 (br s, 1H), 2.57 (s, 3H), 1.60 (s, 6H)

[0939] The compounds listed in Table II were prepared in a similar manner.

[0940] Table II

[0941]

[0942]

[0943] * HPLC: High Performance Liquid Chromatography; HPLC - column Kinetex XB C18 1,7 μ (50 × 2,1 mm); Eluent: acetonitrile / water + 0.1% trifluoroacetic acid (gradient from 5:95 to 100:0 in 1.5 min at 60 °C, flow rate gradient from 0.8 to 1.0 ml / min in 1.5 min).

[0944] Rt: Retention time in minutes.

[0945] 3. Preparation of Compound I.c

[0946]

[0947] 3.1 Preparation of 5-[6-(difluoromethyl)-5-methyl-3-pyridyl]-2,2,3-trimethyl-3H-1,4-benzoxazine (Exemplary Compound 58 in Table III)

[0948] 3.1a) Preparation of 2,2,3-trimethylchroman-4-one oxime

[0949] Hydroxylamine hydrochloride (72.87 g, 3 eq) was added to a solution of 2,2,3-trimethylchroman-4-one (1 eq, 66.5 g) in pyridine (423 ml, 15 eq), and the reaction mixture was stirred at 85 °C for 18 h. The reaction solution was poured into water (1000 ml), and the solution was extracted with heptane, washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give the title compound as a brown powder (66.6). The title compound was used directly without further purification.

[0950] 1 H NMR (400 MHz, CDCl 3 ): δ [ppm]: 9.15 (s, 1H), 7.75 (dd, J = 7.9, 1.7 Hz, 1H), 7.26 (dd, J = 7.1, 1.5 Hz, 1H), 6.91 (ddd, J = 8.2, 7.2, 1.2 Hz, 1H), 6.86 (dd, J = 8.3, 1.2 Hz, 1H), 3.39 (q, J = 7.0 Hz, 1H), 1.45 (s, 3H), 1.27 (s, 3H), 1.13 (d, J = 7.0 Hz, 3H).

[0951] 3.1b) Preparation of 2,2,3-trimethyl-3,4-dihydro-1,4-benzoxazin-5-one

[0952] At a temperature below 30 °C, 2,2,3-trimethylchroman-4-one oxime (66 g, 1 eq) was added to thionyl chloride (80, 3.5 eq), and the reaction mixture was stirred at 50 °C for 17 h. After removing thionyl chloride in vacuo, the residue was poured into 1,4-dioxane (500 ml) and water (200 ml), and stirred at 80 °C for 1 h. After removing 1,4-dioxane in vacuo, the resulting residue was extracted with ethyl acetate, washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the crude product was purified by flash column chromatography on silica gel using heptane / MTBE as the eluent to give the title compound as a powder (25.4 g).

[0953] 11H NMR (400 MHz, CDCl 3 ): δ [ppm]: 7.74 (dd, J = 7.7, 1.8 Hz, 1H), 7.44 (td, J = 7.7, 1.8 Hz, 1H), 7.20 (td, J = 7.5, 1.1 Hz, 1H), 6.98 (dd, J = 8.1, 1.1 Hz, 1H), 6.44 (s, 1H), 3.37 (qd, J = 6.9, 5.2 Hz, 1H), 1.39 (s, 3H), 1.29 (s, 3H), 1.20 (d, J = 6.9 Hz, 3H).

[0954] 3.1c) Preparation of 5-chloro-2,2,3-trimethyl-3H-1,4-benzoxazepine

[0955] A mixture of 2,2,3-trimethyl-3,4-dihydro-1,4-benzoxazepin-5-one (10 g, 1 eq) with phosphoryl chloride (100 mL) and phosphorus pentachloride (11.67 g, 1.15 eq) was stirred and heated at 110 °C for 2 h. After cooling, the reaction solution was concentrated in vacuo, diluted with dichloromethane, washed twice with saturated sodium carbonate solution, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give the crude product (10.8 g). The title compound was used directly without further purification.

[0956] 3.1d) 5-[6-(Difluoromethyl)-5-methyl-3-pyridyl]-2,2,3-trimethyl-3H-1,4-benzoxazepin Preparation

[0957] [6-(Difluoromethyl)-5-methyl-3-pyridyl]boronic acid (3.11 g, 1.2 eq), potassium carbonate (3.83 g, 2 eq), silver oxide (1.61, 0.5 eq) and dichlorobis(triphenylphosphine)-palladium(II) (490 mg, 0.05 eq) were added to a solution of 5-chloro-2,2,3-trimethyl-3H-1,4-benzoxazepine (3.1 g, 1 eq) in dry tetrahydrofuran (57 mL), and the mixture was stirred at 80 °C for 18 h under an argon atmosphere. After cooling, the reaction solution was diluted with ethyl acetate, and the solution was washed successively with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The crude product was purified by high performance liquid chromatography on silica RP-18 using acetonitrile / water as the eluent to give the title compound as a white powder (1.5 g).

[0958] 1 1H NMR (400 MHz, CDCl 3): d [ppm]: 8.58 (d, J = 1.9 Hz, 1H), 7.92 (s, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.18 (td, J = 7.5, 1.2 Hz, 1H), 7.09 (td, J = 7.7, 1.4 Hz, 2H), 6.73 (t, J = 54.5 Hz, 1H), 3.28 (d, J = 6.8 Hz, 1H), 2.54 (d, J = 2.2 Hz, 3H), 1.59 (s, 3H), 1.45 (s, 3H), 1.39 (s, 3H).

[0959] The compounds listed in Table III are prepared in a similar manner.

[0960] Table III

[0961]

[0962]

[0963]

[0964]

[0965] B. Fungicidal Activity

[0966] I. General

[0967] Sensitivity test in microtiter format

[0968] The active substances are separately formulated as stock solutions in dimethyl sulfoxide (DMSO) at a concentration of 10,000 ppm.

[0969] Selection of resistant strains

[0970] The active substances are separately formulated as stock solutions in dimethyl sulfoxide (DMSO) at a concentration of 10,000 ppm.

[0971] Botrytis cinerea spores (in the range of 10 7 –10 8 are plated on DOB agar plates (3.4 g / l YNB (Becton Dickinson), 10 g / l ammonium sulfate, 40 g / l glucose, 20 g / l agar) amended with different lethal concentrations of the active ingredient to select for spontaneous mutants. After 7 - 14 days, the growing colonies are transferred to DOB agar plates amended with the same lethal concentration of the active ingredient and then further propagated on oatmeal agar medium (50 g / l oatmeal agar (Sigma), 15 g / l agar (Difco)) for sensitivity testing.

[0972] Detection of mutations

[0973] Mutations in the target genes of resistant strains can be detected by well-known nucleic acid-level methods (e.g., Sanger sequencing and pyrosequencing).

[0974] II. Examples

[0975] 1. Example 1: Activity against Botrytis cinerea in microtiter tests

[0976] 1.1 General procedure for determining antifungal activity

[0977] Fungal strains used:

[0978] a) Botrytis cinerea (sensitive, wild type)

[0979] b) Various mutants of Botrytis cinerea

[0980] Spores of Botrytis cinerea were harvested from oatmeal agar plates (50 g / l oatmeal agar (Sigma, Art. O-3506), 15 g / l agar (Difco)) using a cotton swab, immersed in 3 ml of double-concentrated DOB-medium (3.4 g / l YNB (Becton-Dickinson), 10 g / l ammonium sulfate, 40 g / l glucose, adjusted to pH 7), and the spore suspension was adjusted to a spore density of 3.2×10 4 spores / ml. Before use, the compound solution was serially diluted in several steps from the stock solution in (dimethyl sulfoxide) DMSO. The high test concentration was 50 mg / L (ppm) or 31 mg / L (ppm). The compound solution was transferred to an empty microplate and filled with an equal volume of spore suspension.

[0981] Antifungal activity was determined by measuring the turbidity of the culture at 620 nm in a 96-well microplate in the presence of the test compound after incubation for 7 days. The blank value (growth medium + compound, without spores) was subtracted from each concentration of the spore suspension. The relative antifungal activity was calculated by comparing the effect of the test compound with the effect of the DMSO control. The results are shown in Table IV (for compounds of general formula I.A), Table VI (for compounds of general formula I.B), and Table VIII (for compounds of general formula I.C).

[0982] Showing that the IC 50 value of mutant strain IC 50 (MUT) is equal to or lower than the IC 50 observed for the wild-type strain IC 50Compounds of the value are considered to be particularly active as DHODH inhibitors ("AA") and are thus particularly useful against the corresponding Botrytis cinerea mutant strains.

[0983] Showing IC 50 (MUT) significantly lower than 31 mg / L and IC 50 (MUT) and IC 50 (WT) in the range of 1 to 100 are considered to be active as DHODH inhibitors ("A") and are thus useful against the corresponding Botrytis cinerea mutant strains.

[0984] Showing IC 50 (MUT) higher than IC 50 (WT) and showing IC 50 (MUT) and IC 50 (WT) in the range higher than 100 are considered to be unsuitable as DHODH inhibitors ("I").

[0985] The absolute IC 50 values (concentrations of the test compound that result in 50% inhibition of fungal growth) are calculated from the obtained dose responses of each compound and strain.

[0986] The results are reported in Table V (for compounds of general formula I.A), Table VII (for compounds of general formula I.B), and Table IX (for compounds of general formula I.C).

[0987] The initial concentration of the test compound and several dilution steps allow the evaluation of IC 50 values from 0.0032 to 50 mg / L (ppm) (1:5 dilution) or from 0.0001 to 31 mg / L (ppm) (1:4 dilution), as shown in the table.

[0988] 1.2 Results

[0989] 1.2.1 Results of Compounds of General Formula I.A

[0990]

[0991] 1.2.1.1 Relative Antifungal Activity of Compounds of General Formula I.A

[0992] Table IV: Relative Antifungal Activity Expressed as IC 50 Values (ppm) Obtained for Compounds of General Formula I.A According to the Invention

[0993]

[0994]

[0995]

[0996]

[0997]

[0998]

[0999]

[1000]

[1001]

[1002]

[1003] 1.2.1.2 Absolute Antifungal Activity of Compounds with General Formula I.A

[1004] The following data show the absolute IC obtained when a group of compounds with general formula I.A and comparative compounds (as shown in Table V) were screened for activity according to the general procedure outlined above 50 Comparison between.

[1005]

[1006]

[1007]

[1008]

[1009] 1.2.2 Results of Compounds with General Formula I.B

[1010]

[1011] 1.2.2.1 Relative Antifungal Activity of Compounds with General Formula I.B

[1012] Table VI: Relative antifungal activity obtained for compounds with general formula I.B according to the present invention, expressed as IC 50 (ppm).

[1013]

[1014]

[1015] 1.2.2.2 Absolute Antifungal Activity of Compounds with General Formula I.B

[1016] The following data shows the absolute IC obtained when a group of compounds of general formula I.B and comparative compounds (as shown in Table VII) were screened for activity according to the general procedure outlined above. 50 Comparison between.

[1017]

[1018] 1.2.3 Results for compounds of general formula I.C

[1019]

[1020] 1.2.3.1 Relative antifungal activity of compounds of general formula I.C

[1021] Table VIII: Relative antifungal activity expressed as IC 50 (ppm) obtained for compounds of general formula I.C according to the present invention.

[1022]

[1023]

[1024]

[1025]

[1026]

[1027]

[1028] 1.2.3.2 Absolute antifungal activity of compounds of general formula I.C

[1029] The following data shows the absolute IC obtained when a group of compounds of general formula I.C and comparative compounds (as shown in Table IX) were screened for activity according to the general procedure outlined above. 50 Comparison between

[1030]

[1031] 2. Example 2: Activity against Sclerotinia sclerotiorum in a tissue culture plate assay using mycelial plugs

[1032] 2.1 General procedure for determining antifungal activity

[1033] Fungal strains used:

[1034] a) Sclerotinia sclerotiorum (sensitive, wild type)

[1035] b) Mutants of Sclerotinia sclerotiorum

[1036] The pure culture was grown on DOB-agar medium (3.4 g / l YNB (Becton Dickinson), 10 g / l ammonium sulfate, 40 g / l glucose) at 18 °C for 5 - 7 days. Mycelial plugs (6 mm diameter) taken from the colony edge were used as inoculum for the sensitivity test. 500 μl of fungicide-amended DOB medium (3.4 g / l YNB (Becton Dickinson), 10 g / l ammonium sulfate, 40 g / l glucose, adjusted to pH 7) was added to each well of a 24-well tissue culture plate. Each well was then inoculated with a mycelial plug with the mycelial surface facing upwards. Two replicate wells were used for each isolate and fungicide concentration. After incubation at 18 °C in the dark for 7 days, growth was evaluated by estimating the % growth in the wells. The IC 50 value (the concentration of the test compound that results in 50% inhibition of fungal growth) was calculated from the resulting dose-response for each compound and strain.

[1037] 2.2 Results

[1038] 2.2.1 Absolute antifungal activity of compounds of formula I.A and comparative compounds

[1039]

[1040] The results are shown in Table X.

[1041]

[1042]

[1043] 2.2.2 Absolute antifungal activity of compounds of formula I.B and comparative compounds

[1044]

[1045] The results are shown in Table XI.

[1046]

[1047] 2.2.3 Absolute antifungal activity of compounds of formula I.C and comparative compounds

[1048]

[1049] The results are shown in Table XII.

[1050]

[1051] Sequence summary:

[1052]

[1053]

[1054]

[1055] AA = amino acid

[1056] NA = nucleic acid

[1057] The disclosures of any documents cited above are incorporated by reference.

Claims

1. Use of a compound of formula I or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt against plant pathogenic fungi resistant to dihydroorotate dehydrogenase inhibitors wherein R 1 is hydrogen, halogen, CN, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 2 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyloxy or C 2 -C 6 -alkynyloxy; R 3 is hydrogen, a halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyloxy or C 2 -C 6 -alkynyloxy; R 4 is hydrogen, halogen, CN, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 5 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the last-mentioned eight aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 5a ; wherein Each R 5a independently is halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy; R 6 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 6a ; wherein Each R 6a independently is halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy; or R 5 and R 6 together form an oxo group (=O); or R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing 1, 2 or 3 heteroatoms selected from O and S as ring members; wherein the carbon ring or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 wherein Each R 56 is independently a halogen, C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl; R 7 is hydrogen, a halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 7a ; wherein Each R 7a is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy; R 8 is hydrogen, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, where the last-mentioned 8 aliphatic or aromatic groups are unsubstituted or carry 1, 2 or 3 substituents R 8a ; where Each R 8a is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy; or R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing 1, 2 or 3 heteroatoms selected from O and S as ring members; Each X is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; Y is O when m is 1; and is O or NR when m is 0 9 ; wherein R 9 is hydrogen, CN, CH 2 CN, CH(CH 3 )CN, CH(=O), -C(=O)C 1 -C 6 -alkyl, -C(=O)C 2 -C 6 -alkenyl, -C(=O)C 2 -C 6 -alkynyl, -C(=O)C 3 -C 6 -cycloalkyl, -C(=O)-N(H)C 1 -C 4 -alkyl, -C(=O)-N(C 1 -C 4 -alkyl) 2、 C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 4 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, -S(=O) 2 -R 9a , a five- or six-membered heteroaryl, aryl or benzyl; wherein the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O and S as ring members; wherein the benzene rings in the aryl and benzyl are unsubstituted or carry 1, 2, 3, 4 or 5 substituents selected from the group consisting of: CN, halogen, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy; wherein R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, phenyl or benzyl, wherein the benzene ring in the last two mentioned groups is unsubstituted or bears 1, 2 or 3 substituents each independently selected from the group consisting of: halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl and C 2 -C 6 -haloalkynyl; m is 0 or 1; and n is 0, 1, 2 or 3.

2. Use according to claim 1, wherein one, two, three or all four of the following conditions a), b), c) and / or d) apply: a) R 1 and R 4 are hydrogen; b) R 2 and R 3 are each independently C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; wherein preferably R 2 is C 1 -C 4 -alkyl; and R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; c) R 5 and R 6 each independently is hydrogen, C 1 -C 6 -alkyl or phenyl, wherein preferably when m is 0, at least one of R 5 and R 6 is not hydrogen; or R 5 and R 6 together form an oxo group (=O); or R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbon ring or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 ; wherein each R 56 independently is C 1 -C 4 -alkyl; d) Each X is independently halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy or C 1 -C 6 -haloalkoxy; preferably halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy.

3. Use according to any one of the preceding claims, wherein R 7 and R 8 are each independently hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl; or R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring.

4. Use according to any one of the preceding claims, wherein R 9 is hydrogen, -CH(=O), -C(=O)C 1 -C 6 -alkyl, -C(=O)C 2 -C 6 -alkenyl, -C(=O)C 2 -C 6 -alkynyl, -C(=O)C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, -S(=O) 2 -R 9a , a five- or six-membered heteroaryl or phenyl; wherein the heteroaryl contains 1, 2 or 3 heteroatoms selected from N, O and S as ring members; wherein the phenyl is unsubstituted or bears 1, 2, 3, 4 or 5 substituents selected from the group consisting of: CN, halogen, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy; Preferably, R 9 is hydrogen, C 1 -C 4 -alkyl, -C(=O)C 1 -C 3 -alkyl or -S(=O) 2 -R 9a ; wherein R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents.

5. Use according to any one of the preceding claims, wherein R 1 is hydrogen; R 2 is C 1 -C 4 -alkyl; R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 4 is hydrogen; R 5 is hydrogen, C 1 -C 6 -alkyl or phenyl; R 6 is hydrogen, C 1 -C 6 -alkyl or phenyl; Preferably, when m is 0, at least one of R 5 and R 6 is not hydrogen; or R 5 and R 6 together form an oxo group (=O); or R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbocyclic or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 wherein Each R 56 is independently C 1 -C 4 -alkyl; R 7 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl; R 8 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl; or R 7 and R 8 together with the carbon atoms to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring; Each X is independently a halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy; and R 9 is hydrogen, C 1 -C 4 -alkyl, -C(=O)C 1 -C 3 -alkyl or -S(=O) 2 -R 9a ; wherein R 9a is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents.

6. Use according to any one of the preceding claims, wherein R 1 is hydrogen; R 2 is C 1 -C 4 -alkyl; R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 4 is hydrogen; R 5 is hydrogen, C 1 -C 6 -alkyl or phenyl; R 6 is C 1 -C 6 -alkyl or phenyl; or R 5 and R 6 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbon ring or a 3-, 4-, 5- or 6-membered saturated heterocyclic ring containing one oxygen atom as a ring member; wherein the carbon ring or heterocyclic ring is unsubstituted or bears 1, 2 or 3 substituents R 56 wherein Each R 56 is independently C 1 -C 4 -alkyl; Each X is independently halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy; Y is O; and m is 0; and n is 0, 1 or 2; or R 1 is hydrogen; R 2 is C 1 -C 4 -alkyl; R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 4 is hydrogen; R 5 is C 1 -C 6 -alkyl; R 6 is C 1 -C 6 -alkyl; each X is independently halogen; Y is NR 9 ; R 9 is hydrogen, C 1 -C 4 -alkyl, -C(=O)C 1 -C 3 -alkyl or -S(=O) 2 -R 9a ; wherein R 9a is phenyl, wherein the benzene ring is unsubstituted or bears 1, 2 or 3 C 1 -C 4 -alkyl substituents; m is 0; and n is 0, 1 or 2; or R 1 is hydrogen; R 2 is C 1 -C 4 -alkyl; R 3 is C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl; R 4 is hydrogen; R 5 is hydrogen or C 1 -C 6 -alkyl; R 6 is hydrogen or C 1 -C 6 -alkyl; or R 5 and R 6 together form an oxo group (=O); R 7 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl; R 8 is hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl; or R 7 and R 8 together with the carbon atom to which they are attached form a 3-, 4-, 5- or 6-membered saturated carbocyclic ring; Y is O; m is 1; and n is 0.

7. Use according to any one of the preceding claims, wherein the DHODH inhibitor-resistant plant pathogenic fungus contains at least one, particularly 1 to 5, more particularly 1 or 2 resistance-inducing mutations in its endogenous DHODH gene, particularly resulting in at least one difference (e.g., substitution, deletion, insertion, inversion) in the amino acid sequence of the mutant DHODH protein relative to the non-mutant DHODH protein.

8. Use according to any one of the preceding claims, wherein the DHODH inhibitor-resistant plant pathogenic fungus is selected from the genera Alternaria, Bipolaris, Botrytis, Cercospora, Colletotrichum, Corynespora, Fusarium, Gibellulopsis, Diplocarpon, Phaeoisariopsis, Pseudocercospora, Pyricularia, Pyrenophora, Ramularia, Rhynchosporium, Sclerotinia, Zymoseptoria and Venturia.

9. Use according to any one of the preceding claims, wherein the DHODH inhibitor-resistant plant pathogenic fungus contains at least one resistance-inducing mutation in at least one sequence portion corresponding to one of the following non-mutant consensus sequence motifs in the amino acid sequence of its endogenous DHODH enzyme: a)X 1 X 2 X 3 X 4 X 5 X 6 X 7 R (Consensus motif 1) (SEQ ID NO:52) wherein X 1 to X 7 each independently represents any natural amino acid residue and specifically has the following meanings: X 1 = W, F, Y, H or Del, where Del represents a missing amino acid residue X 2 = L, A, I, F or V X 3 = V, L, S or A X 4 = V, T or P X 5 = P, A or M X 6 = A, L, V, I, T or F X 7 = L, V, M or I b) D X 2 E X 4 A H X 7 X 8 G (Consensus motif 2) (SEQ ID NO:53) wherein X2 to X8 independently of one another represent any natural amino acid residue and particularly have the following meanings: X2 = A, G or P X4 = D, E X7 = H or Q X8 = V, A, F, S or M c) L X2 X3 X4 G X6 X7 X8 V E (Consensus motif 3) (SEQ ID NO:54) wherein X2 to X8 independently of one another represent any natural amino acid residue and particularly have the following meanings: X2 = F, M or L X3 = E, A, D or S X4 = L, V or M X6 = P or A X7 = A or G X8 = I or V d) X 1 Q X 3 G N X 6 X 7 P R X 10 F R (Consensus motif 4) (SEQ ID NO:55) wherein X 1 to X 10 each independently represents any natural amino acid residue and particularly has the following meanings: X 1 = P or A X 3 = D, E, P, A, L or K X 6 = P or D X 7 = K, R or Q X 10 = V or M e)N R Y G X 5 N S (Consensus motif 5) (SEQ ID NO:56) wherein X 5 = any natural amino acid residue, and in particular L or F f)X 1 X 2 X 3 Y G G X 7 G T X 10 X 11 R X 13 K (Consensus motif 6) (SEQ ID NO:57) wherein X 1 to X 13 each independently represents any natural amino acid residue and particularly has the following meanings: X 1 = A, G, S or K X 2 = M, L, R or I X 3 = I, V, M or T X 7 = A, S, V or P X 10 = I or V X 11 = T, G or S X 13 = I, M, or V.

10. Use according to claim 9, wherein the endogenous DHODH enzyme is selected from enzymes comprising at least one amino acid sequence selected from SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 or 51, or a sequence having at least 70% sequence identity with any one of said sequences.

11. Use according to any one of the preceding claims, wherein the DHODH inhibitor-resistant phytopathogenic fungus is a Botrytis cinerea species and contains at least one resistance-inducing mutation in at least one of the following wild-type sequence motifs of its wild-type DHODH comprising the amino acid sequence of SEQ ID NO: 1 a) WLVVPALR (motif 1) (SEQ ID NO: 58) corresponding to amino acid residues 91 to 98 of SEQ ID NO: 1 b) DAEDAHHVG (motif 2) (SEQ ID NO: 59) corresponding to amino acid residues 103 to 111 of SEQ ID NO: 1 c) LFALGPAIVE (motif 3) (SEQ ID NO: 60) corresponding to amino acid residues 169 to 178 of SEQ ID NO: 1 d) AQDGNPKPRVFR (motif 4) (SEQ ID NO: 61) corresponding to amino acid residues 186 to 197 of SEQ ID NO: 1 e) NRYGLNS (motif 5) SEQ ID NO: 62 corresponding to amino acid residues 206 to 212 of SEQ ID NO: 1 f) AMVYGGAGTITRIK (motif 6) SEQ ID NO: 63 corresponding to amino acid residues 492 to 505 of SEQ ID NO: 1; wherein preferably, the DHODH inhibitor-resistant phytopathogenic fungus is a Botrytis cinerea species and contains at least one resistance-inducing mutation in the wild-type sequence of SEQ ID NO: 1 or a sequence having at least 70% identity therewith, wherein the mutant is selected from: a) single mutants V94X, especially F, I, L, D, A, G, E or M, more especially I or L A104X, especially T, P, S, D, V, G or E, more especially D A107X, especially T, P, S, D, V, G or E, more especially T or V H108X, especially Q, P, R, L, D, Y or N, more especially P Del109, G111X, especially E, A, V, R, D, C, W or S, more especially R, V or E L172X, especially F, I, S, V, H, P, R, Q or M, more especially F V195X, especially F, I, L, D, A, G, E or M, more especially F, E or D, especially F Y208X, especially S, C, F, N, H or D, more especially H V494X, particularly F, I, L, D, A, G, E or M, more particularly G G497X, particularly E, A, V, R, D, C, W or S, more particularly V wherein Del represents a deletion of an amino acid residue, and X represents any natural, particularly any naturally induced resistance amino acid residue; and b) multi-mutants comprising a combination of at least 2 of the single mutations of induced resistance as defined above under a), particularly double mutants selected from the following: V195X / A107X, more particularly V195F / A107V and V195F / A107T; and V195X / V494X, more particularly V195F / V494G wherein X represents any natural, particularly any naturally induced resistance amino acid residue.

12. The use according to any one of claims 1 to 10, wherein the DHODH inhibitor-resistant phytopathogenic fungus is different from Botrytis cinerea and contains at least one mutation of induced resistance at an amino acid sequence position similar to that of the mutant of the non-mutated Botrytis cinerea DHODH amino acid sequence as defined in claim 11.

13. A mutant DHODH inhibitor-resistant DHODH enzyme as defined in any one of claims 7 to 12.

14. A nucleic acid molecule comprising at least one nucleotide sequence encoding the mutant DHODH enzyme according to claim 13, particularly selected from mutant nucleic acid sequences derived from nucleotide sequences according to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50 and sequences having at least 70% sequence identity with any of said sequences, the nucleic acid molecule containing at least one mutation in the nucleotide sequence encoding the mutant DHODH enzyme.

15. A method for combating a phytopathogenic fungus as defined in any one of claims 1 and 7 to 12, the method comprising: treating the phytopathogenic fungus as defined in any one of claims 1 or 7 to 12 or a material, plant, soil or seed at risk of being diseased due to a phytopathogenic fungus as defined in any one of claims 1 or 7 to 12 with an effective amount of at least one compound of formula I as defined in any one of claims 1 to 6 or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt, or with an effective amount of a composition comprising at least one compound of formula I as defined in any one of claims 1 to 6 or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt; wherein the method particularly comprises the following steps: a) identifying a phytopathogenic fungus as defined in any one of claims 1 or 7 to 12, or a material, plant, soil or seed at risk of being diseased due to a phytopathogenic fungus as defined in any one of claims 1 or 7 to 12, and b) treating said fungi or these materials, plants, soil or seeds with an effective amount of at least one compound of formula I as defined in any one of claims 1 to 6 or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt, or with an effective amount of a composition comprising at least one compound of formula I as defined in any one of claims 1 to 6 or its N-oxide, tautomer, stereoisomer or agriculturally acceptable salt

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