Pyrido[2,3-E]oxazine derivatives as pesticides

Abstract

The present invention relates to picolinic acid derivatives that are useful for treating fungal diseases, particularly fungal diseases of crop plants. [C1] TIFF2023513464000086.tif42169

Description

Technical Field

[0001] The present invention relates to picolinic acid derivatives useful for treating mycosis.

Background Art

[0002] In view of the increasing global food demand, new treatments for reducing losses of food crops due to diseases, insects, and weeds are internationally required. Worldwide, more than 40% of crops are lost before harvest and 10% are lost after harvest. The losses have actually been increasing since the mid-1990s.

[0003] New threats contributing to this are the emergence of chemically resistant organisms, such as glyphosate-resistant weeds in the United States and strobilurin-resistant strains of Septoria fungal species.

[0004] Recent research also suggests that, probably as a result of global warming, the geographical spread of many crop diseases and pests is increasing.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Non-Patent Document 11

Non-Patent Document 12

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of certain embodiments of the present invention is to provide a pesticide (e.g., a fungicide) that is non-selectively active, i.e., has broad-spectrum activity, or is specifically active against a selected target organism.

[0008] An object of certain embodiments of the present invention is to provide a compound that has lower persistence in the environment after use than compounds of the prior art. Alternatively or additionally, the compounds of the present invention may be less bioaccumulative than compounds of the prior art once they enter the food chain.

[0009] Another object of certain embodiments of the present invention is to provide a compound that is less harmful to humans than compounds of the prior art. Alternatively or additionally, the compounds of the present invention may be less harmful than compounds of the prior art to one or more of the following groups: amphibians, fish, mammals (including domestic animals such as dogs, cats, cows, sheep, pigs, goats, etc.), reptiles, birds, and beneficial invertebrates (e.g., bees and other insects, or worms), beneficial nematodes, beneficial fungi, and nitrogen-fixing bacteria.

[0010] The compounds of the present invention may be as active as compounds of the prior art or more active than compounds of the prior art. They may be active against organisms that have developed resistance to compounds of the prior art. However, the present invention may also relate to compounds having low or equivalent levels of activity compared to the activity of compounds of the prior art. These low-activity compounds are still effective as fungicides but may have other advantages compared to existing compounds, such as reduced environmental impact.

[0011] The compounds of the present invention can be more selective than the compounds of the prior art, i.e., they can have better, equal or slightly lower activity against the target species than the compounds of the prior art, but can have significantly lower activity against non-target species (e.g., protected crops).

[0012] Certain embodiments of the present invention provide compounds that achieve one or more of the above objectives. The compounds may be active per se or may be metabolized or reacted in an aqueous medium to yield an active compound.

Means for Solving the Problems

[0013] In a first aspect of the present invention, a compound of formula I, or an agriculturally acceptable salt or N-oxide thereof:

[0014]

Chemical Formula

[0015] [wherein, X 1 and X 2 are each independently selected from carbon and nitrogen; Y 1 is independently selected from O and S; =Y 2 is independently selected from =O and =S; Z 1 is independently absent or is C(O)O, OC(O), O, S, S(O), S(O)2, C(O)NR 5 , NR 5 C(O), S(O)2NR 5 , NR 5 S(O)2, S(O)NR 5 , NR 5 S(O), CR 6 R 7 , C(O), C(S), C=NOR 8 , C1-C3-alkylene and NR 5 selected from; R 1 and R 12is, in each occurrence independently, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, halogen, nitro, OR 9 、SR 10 、OS(O)2R 10 、S(O)2R 10 、C(O)OR 10 、C(O)NR 10 R 10 、C(O)R 10 、S(O)2NR 10 R 10 、S(O)(NR 10 )R 10 、S(O)R 10 、cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR 10 R 11 selected from; R 2 is, in each occurrence independently, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, halogen, nitro, OR 9 、SR 10 、OS(O)2R 10 、S(O)2R 10 、C(O)OR 10 、C(O)NR 10 R 10 、C(O)R 10 、S(O)2NR 10 R 10 、S(O)(NR 10 )R 10 、S(O)R 10 、cyano, C2-C6-alkenyl, C2-C6-alkynyl, NR 10 R 11 、and phenyl optionally substituted with 1 to 5 R 12 groups; R 3 is, in each occurrence independently, C3-C8-alkyl and C0-C3-alkylene-R 3a selected from; where R 3ais, independently at each occurrence, selected from phenyl, 5- or 6-membered heteroaryl, 5-, 6-, 7- or 8-membered heterocycloalkyl and C3-C8-cycloalkyl; said heterocycloalkyl or cycloalkyl group is monocyclic or bicyclic; said heteroaryl or phenyl group is optionally substituted with 1 to 5 R 12 groups, or said heterocycloalkyl or cycloalkyl group is optionally substituted with 1 to 4 R 13 groups; said heterocycloalkyl or cycloalkyl group may optionally be fused to phenyl or 5- or 6-membered heteroaryl, and said heteroaryl or phenyl group is optionally substituted with 1 to 4 R 12 groups; R 4 is, independently at each occurrence, selected from C1-C6-alkyl, C3-C6-cycloalkyl and C1-C6-haloalkyl; R 5 and R 10 are, each independently at each occurrence, selected from H, C3-C6-cycloalkyl, C1-C6-alkyl and benzyl; or when two R 10 groups are attached to the same nitrogen atom, said R 10 groups together with said nitrogen atom form a 4-, 5-, 6- or 7-membered heterocycloalkyl ring; R 6 is, independently at each occurrence, selected from H, C3-C6-cycloalkyl, C1-C6-alkyl, phenyl and 5- or 6-membered heteroaryl; R 7 is, independently at each occurrence, selected from H, halo and OR 8 ; R 8 is, each independently at each occurrence, selected from H, C3-C6-cycloalkyl, C1-C6-alkyl and C1-C3-alkylene-R 8a wherein R 8a is, independently at each occurrence, selected from phenyl and 5- or 6-membered heteroaryl; R 9is, independently at each occurrence, selected from H, C1-C6-alkyl, C0-C3-alkylene-C3-C6-cycloalkyl, C(O)-C1-C6-alkyl and C1-C6-haloalkyl; R 11 is, independently at each occurrence, selected from H, C1-C6-alkyl, C(O)-C1-C6-alkyl and S(O)2-C1-C6-alkyl; or R 10 group and R 11 group are attached to the same nitrogen atom, said R 10 and R 11 group, together with said nitrogen atom, form a 4-, 5-, 6- or 7-membered heterocycloalkyl ring; R 13 is, independently at each occurrence, =O, =S, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl; halogen, nitro, OR 9 , SR 10 , OS(O)2R 10 , S(O)2R 10 , S(O)2NR 10 R 10 , S(O)(NR 10 )R 10 , S(O)R 10 , cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR 10 R 11 selected from; y is an integer independently selected from 0, 1 and 2; m is an integer independently selected from 0, 1, 2 and 3; wherein any of the foregoing alkyl, alkylene, alkenyl, cycloalkyl, heterocycloalkyl (including the case where two R 10 groups, or an R 10 group and an R 11 group together with the nitrogen to which they are attached form a heterocycloalkyl ring), alkynyl, C(O)-alkyl, S(O)2-alkyl and benzyl, when chemically possible, =O; =NR a , =NOR a, C1-C4-alkyl, halo, nitro, cyano, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-alkynyl, NR a R b , S(O)2R a , S(O)R a , S(O)(NR a )R a , S(O)2NR a R a , CO2R a , C(O)R a , CONR a R a , OR a and SR a optionally substituted by 1 to 4 substituents each independently selected in each occurrence from the group consisting of; wherein R a is independently selected from H and C1-C4-alkyl; R b is independently H, C1-C4-alkyl, C(O)-C1-C4-alkyl, S(O)2-C1-C4-alkyl] is provided.

[0016] In certain embodiments, the compound of formula I is a compound of formula II:

[0017] [Chemical formula]

[0018] [wherein Y 1 , Y 2 , R 1 , R 2 , R 3 , R 4 , m and y are as defined above for formula I] is.

[0019] In certain embodiments, the compound of formula I is a compound of formula III:

[0020] [Chemical formula]

[0021] [wherein, R 2 , R 3 , R 4 and m are as described above for formula I] is as follows.

[0022] In certain embodiments, the compound of formula I is a compound of formula IV:

[0023]

Chemical formula

[0024] [wherein, Z 1 , R 2 , R 3 , R 4 and m are as described above for formula I] is as follows.

[0025] In certain embodiments, the compound of formula I is a compound of formula V:

[0026]

Chemical formula

[0027] [wherein, Z 1 , R 2 , R 4 , R 12 , and m are as described above for formula I; x is an integer selected from 0, 1, 2, 3, 4, and 5] is as follows.

[0028] In certain embodiments, the compound of formula I is a compound of formula VI:

[0029]

Chemical formula

[0030] [wherein, R 2 , R 4 , R12 and m is as described above for formula I; x is an integer selected from 0, 1, 2, 3, 4, and 5] is as follows.

[0031] The following embodiments apply to any of the compounds of formulas (I) - (VI). These embodiments are independent and interchangeable. Any one embodiment can be combined with any other embodiment, if chemically acceptable. In other words, any of the features described in the following embodiments can be combined with the features described in one or more other embodiments (if chemically acceptable). In particular, when a compound is exemplified or described herein, further embodiments can be provided that form part of the present disclosure by combining any two or more of the embodiments listed below, represented at any level of generality and encompassing that compound.

[0032] R 1 is, independently at each occurrence, optionally selected from C1 - C4 - alkyl, halo, and OR 9 may be selected from.

[0033] R 4 is, independently, optionally selected from C1 - C4 - alkyl, C3 - C6 - cycloalkyl, and C1 - C6 - haloalkyl. R 4 is, independently, optionally selected from C1 - C6 - alkyl and C3 - C6 - cycloalkyl. R 4 may be methyl or ethyl. R 4 may be methyl.

[0034] y may be 0.

[0035] Y 1 may be S. Y 1 may be O.

[0036] =Y 2 may be S. =Y 2 may be O.

[0037] X 1 and X 2 may each be carbon. X 1 and X 2 At least one of may be nitrogen. X 1 and X 2 One of may be nitrogen. X 2 may be nitrogen. X 2 is nitrogen, and X 1 may be carbon. X 1 is carbon, and X 2 may be independently selected from carbon and nitrogen.

[0038] m may be 0. m may be 1.

[0039] R 1 , R 2 and R 12 are each independently, in each occurrence, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, halogen, nitro, OR 9 , SR 10 , OS(O)2R 10 , S(O)2R 10 , C(O)OR 10 , C(O)NR 10 R 10 , C(O)R 10 , S(O)2NR 10 R 10 , S(O)(NR 10 )R 10 , S(O)R 10 , cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR 10 R 11 may be selected from. R 2 is independently, in each occurrence, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, halogen, nitro, OR 9 , SR 10 , OS(O)2R 10 , S(O)2R 10 , C(O)OR 10 , C(O)NR 10 R 10, C(O)R 10 , S(O)2NR 10 R 10 , S(O)(NR 10 )R 10 , S(O)R 10 , cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR 10 R 11 may be selected from.

[0040] R 2 is, in each occurrence independently, cyano, nitro, C1-C4-alkyl, halo, O-R 9 , and phenyl optionally substituted with 1 to 5 R 12 groups. R 2 is, in each occurrence independently, cyano, nitro, C1-C4-alkyl, halo and O-R 9 may be selected from.

[0041] R 2 is, in each occurrence independently, phenyl optionally substituted with 1 to 5 R 12 groups.

[0042] R 2 is phenyl substituted with one R 12 group. R 2 is R 12 substituted phenyl, where R 12 is halogen.

[0043] R 2 may be unsubstituted phenyl.

[0044] Z 1 may not be present, or may independently be selected from C(O)O, OC(O), O, S, S(O), S(O)2, C1-C3-alkylene and N(C1-C4-alkyl). Z 1 may not be present, or may independently be selected from C(O)O, OC(O), O, S, C1-C3-alkylene and N(C1-C4-alkyl). Z1 may independently be selected from C1-C3-alkylene, S, N(C1-C4-alkyl), and O. Z 1 may independently be selected from C1-alkylene, S, N(C1-C4-alkyl), and O. Z 1 may independently be selected from S, N(C1-C4-alkyl), and O. Z 1 may independently be selected from C1-alkylene, S, and O. Z 1 may be absent or may independently be selected from C1-C3-alkylene and O. Z 1 may be absent or may be O. Z 1 may be O. Z 1 may be a group selected from S and O. Z 1 may be absent. Z 1 may be C(O)O. Z 1 may be S. Z 1 may be C1-C3-alkylene. Z 1 may be C1-alkylene. Z 1 may be N(C1-C4-alkyl), for example N-Me. Exemplary C1-alkylene groups that Z1 may be include CH2, CH(OH), C(NHOR a ) and C(O).

[0045] R 3 may be CH2R 3a Alternatively, R 3 may be R 3a

[0046] R 3a may be phenyl which may optionally be substituted, for example unsubstituted phenyl. R 3 may be phenyl which may optionally be substituted, for example unsubstituted phenyl.

[0047] R 3 has the structure:

[0048] ​ [Chemical formula]

[0049] [wherein, x is an integer selected from 0, 1, 2, 3, 4, and 5] may have.

[0050] Z 1 -R 3 has the structure:

[0051] [Chemical formula]

[0052] [wherein, x is an integer selected from 0, 1, 2, 3, 4, and 5] may have.

[0053] x may be at least 1. x may be 0. x may be 1. x may be 2 or 3.

[0054] R 12 is, in each occurrence, independently, cyano, nitro, C1-C4-alkyl, C1-C4-haloalkyl, halo, and S-R 10 , O-R 9 and may be selected from. R 12 is, in each occurrence, independently, cyano, nitro, C1-C4-alkyl, halo, and S-R 10 , O-R 9 and may be selected from. R 12 is, in each occurrence, independently, C1-C4-alkyl, C1-C4-haloalkyl, and halo and may be selected from. R 12 is, in one occurrence, para to Z 1 and may be located at. R 12 is, for example, chloro and may be halo. R 12 is, in one occurrence, ortho to Z 1 and may be located at. R 12 is, in one occurrence, ortho to Z 1It may be located at the meta position with respect to it.

[0055] R 9 may, in each occurrence, independently be selected from H, C1-C6-alkyl, C3-C6-cycloalkyl, C(O)-C1-C6-alkyl, and C1-C6-haloalkyl. R 9 may, in each occurrence, independently be selected from C1-C6-alkyl and C0-C3-alkylene-C3-C6-cycloalkyl. R 3 may be a heteroaryl which may optionally be substituted, for example, a 6-membered heteroaryl which may optionally be substituted. R 3 may be a pyridine which may optionally be substituted. R 3 may independently be selected from phenyl which may optionally be substituted and pyridine which may optionally be substituted.

[0056] R 3 may be a 5-, 6-, 7-, or 8-membered heterocycloalkyl which may optionally be substituted. R 3 may be a 6-membered heterocycloalkyl which may optionally be substituted, for example, piperidine or piperazine.

[0057] R 3 may be selected from C3-C8-alkyl and C0-C3-alkylene-R 3a wherein R 3a is C3-C8-cycloalkyl. R 3 may be C3-C8-alkyl. R 3 may be C3-C6-alkyl. R 3 may be C5-C8-alkyl. R 3 may be C4-alkyl. R 3 may be selected from butyl, isobutyl, sec-butyl, and tert-butyl. R 3 may be selected from isobutyl and sec-butyl. R 3 may be isobutyl. R 3is C0-C3-alkylene-R 3a may be, where R 3a is C3-C8-cycloalkyl. R 3 may be C1-C3-alkylene-R 3a where R 3a is C3-C8-cycloalkyl. R 3 is CH2-R 3a where R 3a is C3-C8-cycloalkyl. R 3 may be C3-C8-cycloalkyl. The said R 3 group may be unsubstituted. The said R3 group may be substituted with 1 to 4 groups selected from F and C1-C2-alkyl.

[0058] R 3 is

[0059]

Chemical formula

[0060] may have a structure selected from

[0061] The compound of formula (I) is

[0062]

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0063] may be selected from

[0064] The present invention is further defined by the following numbered clauses: 1. A compound of formula I, or an agriculturally acceptable salt or N-oxide thereof:

[0065] [Chem.]

[0066] [wherein, X 1 and X 2 are each independently selected from carbon and nitrogen; Y 1 is independently selected from O and S; =Y 2 is independently selected from =O and =S; Z 1 is independently absent or is selected from C(O)O, OC(O), O, S, S(O), S(O)2, C(O)NR 5 , NR 5 C(O), S(O)2NR 5 , NR 5 S(O)2, S(O)NR 5 , NR 5 S(O), CR 6 R 7 , C(O), C(S), C=NOR 8 , C1-C3-alkylene and NR 5 ; R 1 , R 2 and R 12 are each independently, in each occurrence, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, halogen, nitro, OR 9 , SR 10 , OS(O)2R 10 , S(O)2R 10 , C(O)OR 10 , C(O)NR 10 R 10 , C(O)R 10 , S(O)2NR 10 R 10 , S(O)(NR 10 )R10 、 S(O)R 10 、 cyano, C2-C6 alkenyl, C2-C6 alkynyl, and NR 10 R 11 selected from; R 3 is, independently at each occurrence, C3-C8 alkyl and C0-C3 alkylene-R 3a selected from; where R 3a is, independently at each occurrence, selected from phenyl, 5- or 6-membered heteroaryl, 5-, 6-, 7- or 8-membered heterocycloalkyl and C3-C8 cycloalkyl; the heterocycloalkyl or cycloalkyl group is monocyclic or bicyclic; the heteroaryl or phenyl group may optionally be substituted with 1-5 R 12 groups, or the heterocycloalkyl or cycloalkyl group may optionally be substituted with 1-4 R 13 groups; the heterocycloalkyl or cycloalkyl group may optionally be fused to phenyl or 5- or 6-membered heteroaryl, and the heteroaryl or phenyl group may optionally be substituted with 1-4 R 12 groups; R 4 is, independently at each occurrence, selected from C1-C6 alkyl, C3-C6 cycloalkyl and C1-C6 haloalkyl; R 5 and R 10 are, independently at each occurrence, each selected from H, C3-C6 cycloalkyl, C1-C6 alkyl and benzyl; or when two R 10 groups are attached to the same nitrogen atom, the R 10 groups together with the nitrogen atom form a 4-, 5-, 6- or 7-membered heterocycloalkyl ring; R 6 is, independently at each occurrence, selected from H, C3-C6 cycloalkyl, C1-C6 alkyl, phenyl and 5- or 6-membered heteroaryl; R 7 is, independently at each occurrence, selected from H, halo and OR 8selected from; R 8 is, in each occurrence independently, H, C3-C6-cycloalkyl, C1-C6-alkyl and C1-C3-alkylene-R 8a selected from; where R 8a is, in each occurrence independently, selected from phenyl and 5- or 6-membered heteroaryl; R 9 is, in each occurrence independently, selected from H, C1-C6-alkyl, C3-C6-cycloalkyl, C(O)-C1-C6-alkyl and C1-C6-haloalkyl; R 11 is, in each occurrence independently, selected from H, C1-C6-alkyl, C(O)-C1-C6-alkyl and S(O)2-C1-C6-alkyl; or R 10 groups and R 11 groups are attached to the same nitrogen atom, said R 10 and R 11 groups together with said nitrogen atom form a 4-, 5-, 6- or 7-membered heterocycloalkyl ring; R 13 is, in each occurrence independently, =O, =S, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl; halogen, nitro, OR 9 , SR 10 , OS(O)2R 10 , S(O)2R 10 , S(O)2NR 10 R 10 , S(O)(NR 10 )R 10 , S(O)R 10 , cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR 10 R 11 selected from; y is an integer independently selected from 0, 1 and 2; m is an integer independently selected from 0, 1, 2 and 3; wherein any of the foregoing alkyl, alkylene, alkenyl, cycloalkyl, heterocycloalkyl (two R 10 groups, or R 10 groups and R11 (including the case where the groups together with the nitrogen to which they are attached form a heterocycloalkyl ring), alkynyl, C(O)-alkyl, S(O)2-alkyl and benzyl, when chemically possible, =O; =NR a , =NOR a , C1-C4-alkyl, halo, nitro, cyano, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-alkynyl, NR a R b , S(O)2R a , S(O)R a , S(O)(NR a )R a , S(O)2NR a R a , CO2R a , C(O)R a , CONR a R a , OR a and SR a and may be optionally substituted by 1 to 4 substituents each independently selected from the group consisting of; wherein R a is independently selected from H and C1-C4-alkyl; R b is independently H, C1-C4-alkyl, C(O)-C1-C4-alkyl, S(O)2-C1-C4-alkyl]. 2. The compound according to clause 1, wherein R 4 is independently selected from C1-C6-alkyl and C3-C6-cycloalkyl. 3. The compound according to clause 1 or 2, wherein y is 0. 4. The compound according to any one of clauses 1 to 3, wherein Y 1 is O. 5. The compound according to any one of clauses 1 to 4, wherein =Y 2 is =S. 6. The compound according to any one of clauses 1 to 5, wherein X 1 is carbon. 7. The compound according to clause 6, wherein X 2 is carbon. 8. X 2The compound according to clause 6, wherein Z is nitrogen. 9. Z 1 is, independently at each occurrence, O, S, C1-alkylene and NR 5 selected from, wherein R 5 is C1-C3-alkyl, the compound according to any one of clauses 1 to 8. 10. Z 1 is O, the compound according to clause 9. 11. R 3 is R 3a is, the compound according to any one of clauses 1 to 10. 12. R 3a is optionally substituted phenyl, the compound according to any one of clauses 1 to 11. 13. R 3 is C3-C8-alkyl, the compound according to any one of clauses 1 to 10. 14. The compound according to any one of clauses 1 to 13, wherein m is 0. 15. The compound of formula (I) is

[0067]

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0068] selected from, the compound according to clause 1. 16. A method for controlling mycosis, comprising applying an agriculturally effective and substantially non-phytotoxic amount of the compound according to any one of clauses 1 to 15 to plant seeds, the plants themselves, or the area where the plants are intended to grow. 17. Use of a compound according to any one of claims 1 to 15 for controlling fungal diseases of plants. 18. A fungicidal composition comprising an active compound according to any one of claims 1 to 15 in an effective and non-phytotoxic amount.

DETAILED DESCRIPTION OF THE INVENTION

[0069] C m ~C n The term refers to a group having m to n carbon atoms.

[0070] The term "alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon chain. For example, C1-C6-alkyl may refer to methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl and n-hexyl. The alkyl group may be unsubstituted or substituted by one or more substituents. Specific substituents for each alkyl group may independently be fluorine, OR a or NHR a and may be.

[0071] The term "alkylene" refers to a straight-chain saturated divalent hydrocarbon chain. The alkylene group may be unsubstituted or substituted by one or more substituents. Specific substituents for each alkylene group may independently be C1-C4-alkyl, fluorine, OR a or NHR a and may be.

[0072] The term "haloalkyl" refers to a hydrocarbon group substituted with at least one halogen atom independently selected in each occurrence from fluorine, chlorine, bromine, and iodine. The halogen atom may be present at any position on the hydrocarbon chain. For example, C1-C6-haloalkyl may refer to chloromethyl, fluoromethyl, trifluoromethyl, chloroethyl, such as 1-chloroethyl and 2-chloroethyl, trichloroethyl, such as 1,2,2-trichloroethyl and 2,2,2-trichloroethyl, fluoroethyl, such as 1-fluoroethyl and 2-fluoroethyl, trifluoroethyl, such as 1,2,2-trifluoroethyl and 2,2,2-trifluoroethyl, chloropropyl, trichloropropyl, fluoropropyl, trifluoropropyl. The haloalkyl group may be a fluoroalkyl group, i.e., a hydrocarbon chain substituted with at least one fluorine atom. Thus, the haloalkyl group may have any amount of halogen substituents. This group may contain a single halogen substituent, which may have two or three halogen substituents, or it may be saturated with halogen substituents.

[0073] The term "alkenyl" refers to a branched or straight-chain hydrocarbon group containing at least one double bond. The double bond may exist as an E or Z isomer. The double bond may be at any possible position in the hydrocarbon chain. For example, "C2-C6-alkenyl" may refer to ethenyl, propenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl, and hexadienyl. The alkenyl group may be unsubstituted or substituted with one or more substituents. The specific substituent for any saturated carbon atom in each alkenyl group may independently be fluorine, OR a or NHR a and may be.

[0074] The term "alkynyl" refers to a branched or straight-chain hydrocarbon chain containing at least one triple bond. The triple bond can be at any possible position in the hydrocarbon chain. For example, "C2-C6-alkynyl" can refer to ethynyl, propynyl, butynyl, pentynyl, and hexynyl. The alkynyl group may be unsubstituted or substituted by one or more substituents. The specific substituents for any saturated carbon atom in each alkynyl group are independently fluorine, OR a or NHR a and can be.

[0075] The term "cycloalkyl" refers to, for example, a saturated hydrocarbon ring system containing 3, 4, 5, or 6 carbon atoms. For example, "C3-C6-cycloalkyl" can refer to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The cycloalkyl group may be unsubstituted or substituted by one or more substituents. The specific substituents for each cycloalkyl group are independently fluorine, OR a or NHR a and can be.

[0076] The term "heterocycloalkyl" can refer to a monocyclic or bicyclic saturated or partially saturated group having the number of atoms shown in the ring system and containing one or two heteroatoms independently selected from O, S, and N (in other words, one or two of the atoms forming the ring system are selected from O, S, and N). Partially saturated means that the ring can contain one or two double bonds. This particularly applies to 5- to 6-membered monocyclic rings. The double bond is typically between two carbon atoms, but can also be between a carbon atom and a nitrogen atom. Examples of heterocycloalkyl groups include piperidine, piperazine, morpholine, thiomorpholine, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, dihydrofuran, tetrahydropyran, dihydropyran, dioxane, azepine. The heterocycloalkyl group may be unsubstituted or substituted by one or more substituents. Specific substituents for any saturated carbon atom in each heterocycloalkyl group are independently fluorine, OR a or NHR a and can be.

[0077] An aryl group can be any aromatic carbocyclic ring system (i.e., a ring system containing 2(2n + 1) π electrons). The aryl group can have 6 to 12 carbon atoms in the ring system. The aryl group is typically a phenyl group. The aryl group can also be a naphthyl group or a biphenyl group.

[0078] In any of the above-described aspects and embodiments, the heteroaryl group may be a 5- to 10-membered ring system of any aromatic (i.e., a ring system containing 2(2n + 1) π electrons), containing 1 to 4 heteroatoms independently selected from O, S, and N (in other words, 1 to 4 of the atoms forming the ring system are selected from O, S, and N). Thus, any heteroaryl group may be a 5-membered heteroaryl group in which the heteroaromatic ring is substituted with 1 to 4 heteroatoms (14 heteroatoms) independently selected from O, S, and N; a 6-membered heteroaryl group in which the heteroaromatic ring is substituted with 1 to 3 (e.g., 1 to 2) nitrogen atoms; a 9-membered bicyclic heteroaryl group in which the heteroaromatic system is substituted with 1 to 4 heteroatoms independently selected from O, S, and N; or a 10-membered bicyclic heteroaryl group in which the heteroaromatic system is substituted with 1 to 4 nitrogen atoms. Specifically, the heteroaryl group may independently be selected from pyrrole, furan, thiophene, pyrazole, imidazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, indazole, benzimidazole, benzoxazole, benzothiazole, benzoisoxazole, purine, quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline, pteridine, phthalazine, naphthyridine.

[0079] In any group that is an aryl or heteroaryl group, the aryl or heteroaryl group may be unsubstituted or, where chemically possible, halo, nitro, cyano, NR a R a 、NR a S(O)2R a 、NR a C(O)R a 、NR a CONR a R a 、NR a CO2R a 、OR a 、SR a 、S(O)Ra 、 S(O)2OR a 、 S(O)2R a 、 S(O)2NR a R a 、 CO2R a C(O)R a 、 CONR a R a 、 CR b R b NR a R a 、 CR b R b OR a 、 C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl and C1-C4 haloalkyl, each independently selected in each occurrence from 1 to 5 substituents which may optionally be substituted; where R a and R b are as described above for formula I.

[0080] Compounds of the present invention containing one or more asymmetric carbon atoms can exist as two or more stereoisomers. When the compounds of the present invention contain a double bond such as a C=C or C=N group, geometric cis / trans (or Z / E) isomers are possible. When structural isomers are interconvertible via a low energy barrier, tautomeric isomerism ("tautomerism") can occur. This can take the form of proton tautomerism, for example, in compounds of the present invention containing an imino, keto, or oxime group, or can take the form of so-called valence tautomerism in compounds containing an aromatic moiety. As a result, a single compound can exhibit more than one type of isomerism.

[0081] Within the scope of the present invention, all stereoisomers, geometric isomers and tautomeric forms of the compounds of the present invention are included, compounds exhibiting more than one type of isomerism, and one or more mixtures thereof.

[0082] The compounds of the present invention can be obtained, stored, and / or used in the form of agriculturally acceptable salts. Suitable salts include, but are not limited to, salts of acceptable inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid, boric acid, sulfamic acid, and hydrobromic acid, or agriculturally acceptable organic acids such as acetic acid, propionic acid, butyric acid, tartaric acid, maleic acid, hydroxymaleic acid, fumaric acid, malic acid, citric acid, lactic acid, mucic acid, gluconic acid, benzoic acid, succinic acid, oxalic acid, phenylacetic acid, methanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, salicylic acid, sulfanilic acid, aspartic acid, glutamic acid, edetic acid, stearic acid, palmitic acid, oleic acid, lauric acid, pantothenic acid, tannic acid, ascorbic acid, and valeric acid. Suitable salts also include salts of inorganic bases and organic bases, for example, salts of counterions such as Na, Ca, K, Li, Mg, ammonium, trimethylsulfonium, etc. The compounds can also be obtained, stored, and / or used in the form of N-oxides. Acid addition salts or base salts in which the counterion is optically active; for example, d-lactate or l-lysine, or racemates; for example, dl-tartrate or dl-arginine are also included.

[0083] Cis / trans isomers can be separated by conventional techniques well known to those skilled in the art, such as chromatography and fractional crystallization.

[0084] Conventional techniques for preparing / isolating individual enantiomers as needed include chiral synthesis from suitable optically pure precursors, or resolution of racemates (or racemates of salts or derivatives) using, for example, chiral high performance liquid chromatography (HPLC). Thus, the chiral compounds (and their chiral precursors) of the present invention can be obtained in enantiomerically enriched form using chromatography, typically HPLC, on an asymmetric resin using a mobile phase consisting of a hydrocarbon, typically heptane or hexane, containing 0 to 50% by volume, typically 2% to 20% isopropanol, and, as a specific example, 0 to 5% by volume of an alkylamine, such as 0.1% diethylamine. By concentrating the eluate, an enriched mixture is obtained.

[0085] Alternatively, the racemate (or racemic precursor) may be reacted with a suitable optically active compound, for example, an alcohol, or if the compound of the invention contains an acidic or basic moiety, with a base or acid such as 1-phenylethylamine or tartaric acid. The resulting mixture of diastereomers may be separated by chromatography and / or fractional crystallization, and one or both of the diastereoisomers may be converted to the corresponding pure enantiomers by means well known to those skilled in the art.

[0086] If any racemate crystallizes, two different types of crystals are possible. The first type is the above-mentioned racemic compound (true racemate) in which one homogeneous form of crystals containing both enantiomers in equimolar amounts is produced. The second type is a racemic mixture or conglomerate in which two forms of crystals each containing a single enantiomer are produced in equimolar amounts.

[0087] Both crystal forms present in the racemic mixture have the same physical properties, but they may have different physical properties compared to the true racemate. The racemic mixture can be separated by conventional techniques known to those skilled in the art - see, for example, "Stereochemistry of Organic Compounds" by E. L. Eliel and S. H. Wilen (Wiley, 1994).

[0088] The activity of the compounds of the invention can be evaluated by various in silico, in vitro and in vivo assays. In silico analysis of various compounds has been demonstrated to predict the final in vitro activity and further the in vivo activity.

[0089] The invention also includes all environmentally acceptable isotope-labeled compounds of Formulas I - VI and their synthesis, in which one or more atoms are replaced by atoms having the same atomic number but a different atomic mass or mass number than is usually found in nature.

[0090] Examples of isotopes suitable for inclusion in the compounds of the present invention include isotopes of hydrogen, such as 2 H and 3 H, isotopes of carbon, such as 11 C, 13 C and 14 C, isotopes of chlorine, such as 36 Cl, isotopes of fluorine, such as 18 F, isotopes of iodine, such as 123 I and 125 I, isotopes of nitrogen, such as 13 N and 15 N, isotopes of oxygen, such as 15 O, 17 O and 18 O, isotopes of phosphorus, such as 32 P, and isotopes of sulfur, such as 35 S.

[0091] Isotopically labeled compounds can generally be prepared by processes similar to the described processes by conventional techniques known to those skilled in the art or by using appropriate isotopically labeled reagents in place of the unlabeled reagents previously used.

[0092] Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of those words, such as "comprising" and "comprises", mean "include but are not limited to", and are not intended to (and do not) exclude other moieties, additives, components, integers or steps.

[0093] Throughout the description and claims of this specification, unless the context otherwise requires, the singular form includes the plural. In particular, when an indefinite article is used, the specification is to be understood as considering not only the singular but also the plural, unless the context otherwise requires.

[0094] Features, integers, characteristics, compounds, chemical moieties or groups described in connection with a particular embodiment, embodiment or example of the invention are to be understood as applicable to any other embodiment, embodiment or example described herein, unless incompatible.

[0095] Where appropriate, the compounds of the invention can be used as fungicides at a particular concentration or application rate.

[0096] According to another aspect of the invention, there is provided a method for controlling a fungal disease, comprising applying an agriculturally effective and substantially non-phytotoxic (to crop plants) amount of a compound of the invention to the seeds of a plant, to the plant itself, or to the area in which the plant is intended to grow.

[0097] The agrochemical can be applied as a seed treatment, foliar spray, stem spray, perfusion or drip irrigation (chemical solution irrigation) to seeds, plants or plant fruits, or to soil or an inert substrate (e.g., inorganic substrates such as sand, rock wool, glass wool; expanded minerals such as perlite, vermiculite, zeolite or expanded clay), pumbe, frangible materials or substances, synthetic organic substrates (e.g., polyurethane), organic substrates (e.g., peat, compost, coir, wood waste such as wood fibers or chips, bark), or liquid substrates (e.g., floating hydroponic systems, nutrient film technology, aeroponics).

[0098] In a further aspect, the invention also relates to a fungicidal composition comprising an effective and non-phytotoxic amount of an active compound of the invention. The composition may further comprise one or more additional fungicides.

[0099] The term "effective and non-phytotoxic amount" means an amount of the pesticidal agent according to the invention which is sufficient to control or destroy any of the target diseases present in or likely to appear in the crop and which does not exert a significant harmful effect on the crop, or actually has a beneficial effect on the plant vigor and yield in the absence of the target organisms. This amount will vary depending on the disease to be controlled, the type of crop, the climatic conditions and the compounds contained in the pesticidal composition. This amount can be determined by systematic field trials within the capabilities of a person skilled in the art.

[0100] Depending on their specific physical and / or chemical properties, the active compounds of the present invention can be formulated as solutions, emulsions, suspension concentrates, powders, foams, pastes, granules, aerosols, microcapsules in polymeric substances and coating materials for seeds, and also as ULV cold and warm spray formulations.

[0101] The active compounds can be used as such or in the form of formulations, for example, ready-to-use solutions, emulsions, aqueous or oily suspension concentrates, powders, wettable powders, pastes, soluble powders, dusts, soluble granules, spreading granules, suspoemulsion concentrates, natural substances impregnated with the active compound, synthetic substances impregnated with the active compound, fertilizers, and also in the form of microcapsules in polymeric substances. Application can be carried out, for example, by watering, spraying, atomizing, spreading, dusting, foaming, diffusion, etc. It is also possible to apply the active compound by the ultra-low volume method or to inject a preparation of the active compound or the active compound itself into the soil. It is also possible to treat the seeds of plants.

[0102] The formulations containing the compounds of the present invention are prepared by known methods, for example, by mixing the compounds with extenders (for example, liquid solvents and / or solid carriers), optionally using surfactants (for example, emulsifiers and / or dispersants and / or foam formers). The formulations are prepared either in a factory / manufacturing plant or either before or during application.

[0103] An adjuvant is a substance suitable for imparting specific properties such as certain technical properties and / or more specific biological properties to the composition itself and / or preparations derived therefrom (e.g., spray liquids, seed coatings). Typical suitable adjuvants are extenders, solvents, and carriers.

[0104] Suitable extenders are, for example, water, polar and non-polar organic chemical liquids such as aromatic and non-aromatic hydrocarbons (e.g., paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes), alcohols and polyols (which may be substituted, etherified and / or esterified where appropriate), ketones (e.g., acetone, cyclohexanone), esters (including fats and oils) and (poly)ethers, unsubstituted and substituted amines, amides, lactams (e.g., N-alkylpyrrolidone) and lactones, sulfones, and sulfoxides (e.g., dimethyl sulfoxide) from the class of substances.

[0105] When the extender used is water, for example, it is also possible to use an organic solvent as a co-solvent. Essentially, suitable liquid solvents are aromatic compounds such as xylene, toluene or alkylnaphthalene; chlorinated aromatic compounds and chlorinated aliphatic hydrocarbons such as chlorobenzene, chloroethylene or methylene chloride; aliphatic hydrocarbons such as cyclohexane or paraffins such as petroleum fractions; alcohols such as butanol or glycol, and also their ethers and esters; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; strongly polar solvents such as dimethylformamide and dimethyl sulfoxide.

[0106] Suitable solid carriers are, for example, ammonium salts and ground natural minerals such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals such as micronized silica, alumina and silicates; suitable solid carriers for granules are, for example, ground and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, and also synthetic granules of inorganic and organic powders, and granules of organic materials such as paper, sawdust, coconut shells, corn cobs and tobacco stalks; suitable emulsifiers and / or foam formers are, for example, nonionic and anionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene aliphatic alcohol ethers such as alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, and furthermore protein hydrolysates; suitable dispersants are nonionic and / or ionic substances such as alcohol-POE and / or -POP ethers, acids and / or POP-POE esters, alkylaryl and / or POP-POE ethers, fatty- and / or POP-POE adducts, POE- and / or POP-polyol derivatives, POE- and / or POP-sorbitan- or -sugar adducts, alkyl or aryl sulfates, alkyl- or aryl sulfonates, and alkyl or aryl phosphates, or those from the class of the corresponding PO-ether adducts. Furthermore, suitable oligomers or polymers are, for example, those derived from vinyl monomers, from acrylic acid, from EO and / or PO, alone or in combination, for example, with (poly)alcohols or (poly)amines. It is also possible to use lignin and its sulfonic acid derivatives, unmodified and modified cellulose, aromatic and / or aliphatic sulfonic acids, and their adducts with formaldehyde.

[0107] Adhesion promoters such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or latexes such as gum arabic, polyvinyl alcohol and polyvinyl acetate, and natural phospholipids such as cephalin and lecithin, and synthetic phospholipids can be used in the formulation.

[0108] Further additives can be mineral and vegetable oils. It is also possible to add colorants such as inorganic pigments such as iron oxide, titanium oxide and Prussian blue, and organic dyes such as alizarin dyes, azo dyes and metal phthalocyanine dyes, and micronutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc. Other possible additives are fragrances, minerals or plants, optionally modified oils and waxes.

[0109] The formulations can also contain stabilizers such as low-temperature stabilizers, preservatives, antioxidants, light stabilizers or other agents which improve chemical and / or physical stability.

[0110] The formulations generally contain from 0.01 to 98% by weight, preferably from 0.1 to 95% by weight, particularly preferably from 0.5 to 90% by weight of the active compound.

[0111] The active compounds according to the invention can also be used, for example, as mixtures with other known fungicides in order to improve the activity spectrum or to reduce or delay the development of resistance. Mixtures with other known active compounds such as nematicides, herbicides, insecticides, acaricides or bactericides are also possible, or mixtures with fertilizers and growth regulators, phytotoxicity reducers or semiochemicals.

[0112] Exemplary application rates of the active compounds according to the invention are, when treating leaves: 0.1 to 10,000 g / ha, preferably 10 to 1000 g / ha, particularly preferably 50 to 300 g / ha (when the application is carried out by spraying or dripping, in particular when an inert substrate such as rock wool or perlite is used, it is also possible to reduce the application rate); when treating seeds: 2 to 200 g per 100 kg of seeds, preferably 2.5 to 150 g per 100 kg of seeds, particularly preferably 2.5 to 25 g per 100 kg of seeds, very particularly preferably 2.5 to 12.5 g per 100 kg of seeds; when treating soil: 0.1 to 10,000 g / ha, preferably 1 to 5000 g / ha.

[0113] The compositions according to the invention are suitable for protecting any plant variety used in agriculture, greenhouses, forests or horticulture, in particular cereals (such as wheat, barley, rye, millet and oats), maize, cotton, soybeans, rice, potatoes, sunflowers, legumes, coffee, beet (such as sugar beet and fodder beet), peanuts, vegetables (such as tomatoes, cucumbers, onions and lettuce), lawns, fruit and nut trees (such as apples, pears, peaches, nectarines, apricots, hazelnuts, pecans, macadamias, pistachios), soft fruits (such as strawberries, raspberries, blackberries, redcurrants), grapes, bananas, cocoa, as well as ornamental plants.

[0114] The active compounds of the invention, in combination with good plant tolerance, favorable toxicity to warm-blooded animals and better environmental tolerance, are suitable for protecting plants and plant organs, increasing yields, improving the quality of harvested products, and controlling diseases encountered in agriculture, horticulture, animal husbandry, forests, gardens and leisure facilities, in the protection of stored products and materials, and also in the health sector, in particular fungal diseases. They can preferably be used as crop protection agents.

[0115] Use as a fungicide The compounds of the invention have activity as fungicides.

[0116] The following are examples of agricultural diseases that can be controlled by the fungicidal compounds: Powdery mildew diseases, for example: diseases caused by Blumeria, for example Blumeria graminis; diseases caused by Podosphaera, for example Podosphaera leucotheca; diseases caused by Sphaerotheca, for example Sphaerotheca fuliginea; diseases caused by Uncinula, for example Uncinula necator; rust diseases, for example: diseases caused by Gymnosporangium, for example Gymnosporangium sabinae; diseases caused by Hemileia, for example Hemileia vastatrix; diseases caused by Phakopsora, for example Phakopsora pachyrhizi or Phakopsora meibomiae; diseases caused by Puccinia, for example Puccinia recondita; diseases caused by Uromyces, for example Uromyces appendiculatus; oomycete diseases, for example: diseases caused by Albugo, for example Albugo Candida; Diseases caused by Bremia, e.g., Bremia lactucae; diseases caused by Peronospora, e.g., Peronospora pisi or Peronospora brassicae; diseases caused by Phytophthora, e.g., Phytophthora infestans; diseases caused by Plasmopara, e.g., Plasmopara viticola; diseases caused by Pseudoperonospora, e.g., Pseudoperonospora humuli or Pseudoperonospora cubensis; diseases caused by Pythium, e.g., Pythium ultimum; Leaf spot diseases, leaf blotch diseases and leaf blight diseases, for example: those caused by Alternaria diseases, such as Alternaria solani; Cercospora diseases, such as Cercospora beticola; Cladiosporum diseases, such as Cladiosporium cucumerinum; Cochliobolus diseases, such as Cochliobolus sativus; Colletotrichum diseases, such as Colletotrichum lindemuthanium; Cycloconium diseases, such as Cycloconium oleaginum; Diaporthe diseases, such as Diaporthe citri; Drechslera, synonym: Helminthosporium or Cochliobolus miyabeanus; Elsinoe diseases, such as those caused by Elsinoe fawcettii; Gloeosporium diseases, such as Gloeosporium laeticolor; Glomerella diseases, such as Glomerella cingulata; Guignardia diseases, such as Guignardia bidwelli; Leptosphaeria diseases, such as Leptosphaeria maculans; Leptosphaeria nodorum;Diseases caused by Magnaporthe, such as those caused by Magnaporthe grisea; diseases caused by Mycosphaerella, such as Mycosphaerella graminicola; Mycosphaerella arachidicola; Mycosphaerella fibensis; diseases caused by Phaeosphaeria, such as those caused by Phaeosphaeria nodorum; diseases caused by Pyrenophora, such as those caused by Pyrenophora teres; diseases caused by Ramularia, such as those caused by Ramularia collo-cygni; diseases caused by Rhynchosporium, such as those caused by Rhynchosporium secalis; diseases caused by Septoria, such as those caused by Septoria apii or Septoria lycopercisi; diseases caused by Typhula, such as those caused by Typhula incarnata; diseases caused by Venturia, such as those caused by Venturia inaequalis; Root and stem diseases, such as: Corticium diseases, such as those caused by Corticium graminearum; Fusarium diseases, such as those caused by Fusarium oxysporum; Gaeumannomyces diseases, such as those caused by Gaeumannomyces graminis; Rhizoctonia diseases, such as those caused by Rhizoctonia solani; Sarocladium diseases, such as those caused by Sarocladium oryzae; Sclerotium diseases, such as those caused by Sclerotium oryzae; Tapesia diseases, such as those caused by Tapesia acuformis; Thielaviopsis diseases, such as those caused by Thielaviopsis basicola; Ear and panicle diseases, including those of maize ear axes, such as: diseases caused by Alternaria, e.g., those caused by Alternaria spp.; diseases caused by Aspergillus, e.g., those caused by Aspergillus flavus; diseases caused by Cladosporium, e.g., those caused by Cladosporium spp.; diseases caused by Claviceps, e.g., those caused by Claviceps purpurea; diseases caused by Fusarium, e.g., those caused by Fusarium culmorum; diseases caused by Gibberella, e.g., those caused by Gibberella zeae; diseases caused by Monographella, e.g., those caused by Monographella nivalis; Smut and bunt diseases, such as: diseases caused by Sphacelotheca, e.g., those caused by Sphacelotheca reiliana; diseases caused by Tilletia, e.g., those caused by Tilletia caries; diseases caused by Urocystis, e.g., those caused by Urocystis occulta; diseases caused by Ustilago, e.g., those caused by Ustilago nuda; Fruit rot and mold diseases, such as those caused by Aspergillus diseases, such as Aspergillus flavus; Botrytis diseases, such as Botrytis cinerea; Penicillium diseases, such as Penicillium expansum; Rhizopus diseases, such as Rhizopus stolonifer; Sclerotinia diseases, such as Sclerotinia sclerotiorum; Verticillium diseases, such as those caused by Verticilium alboatrum; Decay, mold, withering, putrefaction, and damping-off of seeds and soil, for example: those caused by Alternaria diseases, such as Alternaria brassicicola; Aphanomyces diseases, such as Aphanomyces euteiches; Ascochyta diseases, such as Ascochyta lentis; Aspergillus diseases, such as Aspergillus flavus; Cladosporium diseases, such as Cladosporium herbarum; Cochliobolus diseases, such as Cochliobolus sativus (conidial form: Drechslera, Bipolaris, synonym: Helminthosporium); Colletotrichum diseases, such as Colletotrichum coccodes; Fusarium diseases, such as Fusarium culmorum; Gibberella diseases, such as Gibberella zeae; Macrophomina diseases, such as Macrophomina phaseolina; Monographella diseases, such as Monographella nivalis; Penicillium diseases, such as Penicillium expansum; Phoma diseases, such as Phoma lingam; Phomopsis diseases, such as Phomopsis sojae; Phytophthora diseases, such as Phytophthora cactorum; Pyrenophora diseases, such as Pyrenophora graminea; Pyricularia diseases, such as Pyricularia oryzae; Pythium diseases, such as Pythium ultimum; Rhizoctonia diseases, such as Rhizoctonia solani; Rhizopus diseases, such as Rhizopus oryzae;Diseases caused by Sclerotium, such as those caused by Sclerotium rolfsii; Septoria diseases, such as those caused by Septoria nodorum; Tifula diseases, such as those caused by Tifula incarnata; Verticillium diseases, such as those caused by Verticillium dahliae; Cancerous diseases, tengu nest diseases and branch blight diseases, such as: Nectria diseases, such as those caused by Nectria galligena; Sheath blight diseases, such as: Monilinia diseases, such as those caused by Monilinia laxa; Leaf swelling diseases or leaf curl diseases, such as: Exobasidium diseases, such as those caused by Exobasidium vexans; Taphrina diseases, such as those caused by Taphrina deformans; Decline diseases of woody plants, such as: Esca diseases, such as those caused by Phaeomoniella clamydospora, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and Fomitiporia mediterranea; Eutypa dieback, such as those caused by Eutypa lata; Dutch elm disease, such as those caused by Ceratocystis ulmi; Ganoderma diseases, such as those caused by Ganoderma boninense; Diseases of flowers and seeds, such as: Botrytis diseases, such as those caused by Botrytis cinerea; Tuber diseases, for example: Rhizoctonia diseases, for example those caused by Rhizoctonia solani; Helminthosporium diseases, for example those caused by Helminthospohum solani. Clubroot diseases, for example: Plasmodiophora diseases, for example those caused by Plasmodiophora brassicae.

[0117] The compounds of the present invention can be active against a wide range of fungal diseases of plants. Alternatively, they can be specifically active against certain specific fungal diseases.

[0118] Specific fungal diseases against which the compounds of the present invention can be useful include Septoria tritici leaf blotch of wheat, Puccinia triticina leaf rust of wheat, Puccinia striiformis stripe rust of wheat, Venturia inaequalis apple scab, Uncinula necator powdery mildew of grapevine, Rhynchosporium secalis barley leaf blotch, Magnaporthe grisea rice blast, Phakopsora pachyrhizi soybean rust, Leptosphaeria nodorum wheat glume blotch, Blumeria graminis f. sp. tritici powdery mildew of wheat, Blumeria graminis f. sp. hordei powdery mildew of barley, Erysiphe dehor acearum powdery mildew of cucurbitaceae plants, Glomerella lagenarium anthracnose of cucurbitaceae plants, Cercospora beticola leaf spot of beet, Alternaria solani early blight of tomato, and Cochliobolus sativus spot blotch of barley.

[0119] In addition to their fungicidal activity, the compounds of the present invention may also be active against other microorganisms, such as bacteria.

[0120] The fungicidal compounds of the present invention may also be used in the treatment of fungal diseases in humans and animals (e.g., mammals). Similarly, the bactericidal compounds of the present invention may be used in the treatment of bacterial diseases in humans and animals. Accordingly, the present invention includes methods of treating fungal or bacterial diseases, including methods comprising administering a therapeutically effective amount of an antifungal agent of the present invention to a subject in need thereof (e.g., a human subject). The compounds may be formulated for topical administration to the infected area of the body, or may be formulated for oral or parenteral administration.

[0121] Synthesis One skilled in the art will understand that the adaptation of methods known in the art can be applied in the manufacture of the compounds of the present invention.

[0122] For example, those skilled in the art will be immediately familiar with standard textbooks such as "Comprehensive Organic Transformations - A Guide to Functional Group Transformations", RC Larock, Wiley-VCH (since the 1999 edition); "March's Advanced Organic Chemistry - Reactions, Mechanisms and Structure", MB Smith, J. March, Wiley, (since the 5th edition); "Advanced Organic Chemistry, Part B, Reactions and Synthesis", FA Carey, RJ Sundberg, Kluwer Academic / Plenum Publications, (since the 2001 edition); "Organic Synthesis - The Disconnection Approach", S Warren (Wiley), (since the 1982 edition); "Designing Organic Syntheses", S Warren (Wley) (since the 1983 edition); "Heterocyclic Chemistry", J. Joule (Wley since the 2010 edition); ("Guidebook To Organic Synthesis", RK Mackie and DM Smith (Longman) (since the 1982 edition), etc., as well as the references therein.

[0123] Those skilled in the art are familiar with a series of strategies for synthesizing organic and especially heterocyclic molecules, which are common general knowledge as described in textbooks such as Warren's "Organic Synthesis: The Disconnection Approach"; Mackie and Smith's "Guidebook to Organic Chemistry"; and Clayden, Greeves, Warren and Wothers' "Organic Chemistry".

[0124] One of ordinary skill in the art will exercise their judgment and skill regarding the most efficient sequence of reactions for the synthesis of a given target compound and use protecting groups as necessary. This will depend, inter alia, on factors such as the nature of other functional groups present in a particular substrate. Clearly, the type of chemistry involved will affect the choice of reagents used in the synthetic process, the need for and type of protecting groups employed, and the sequence for achieving the protection / deprotection steps. These and other reaction parameters will be apparent to one of ordinary skill in the art by reference to standard textbooks and the examples provided herein.

[0125] Sensitive functional groups may need to be protected and deprotected during the synthesis of the compounds of the present invention. This can be achieved by conventional methods such as those described in, for example, “Protective Groups in Organic Synthesis” by TW Greene and PGM Wuts, John Wiley & Sons Inc. (1999), and references therein.

[0126] Throughout this specification, these abbreviations have the following meanings: TFAA - Trifluoroacetic anhydride NaHMDS - Sodium bis(trimethylsilyl)amide DMSO - Dimethyl sulfoxide aq. - Aqueous conc. - Concentrated DCM - Dichloromethane DMF - N,N-Dimethylformamide h - Hour quant. - Quantitative HPLC - High performance liquid chromatography min - Minute PE - Petroleum ether r.t. - Room temperature sat. - Saturated TFA - Trifluoroacetic acid THF - Tetrahydrofuran

[0127] Certain compounds of the present invention can be accessed according to or similar to the following general synthetic schemes. Certain compounds of the present invention can be accessed according to or similar to Examples 1 to 50 below.

[0128] General synthetic scheme The compounds of formula I can be prepared according to Schemes A - D. Reacting alcohol A with triphosgene (e.g., in the presence of pyridine and DCM at room temperature) can afford the compounds of formula B (a subset of the compounds of formula I).

[0129]

Chemical formula

[0130] Reacting alcohol A with thiophosgene (e.g., in the presence of pyridine and DCM at room temperature) can afford the compounds of formula C (a subset of the compounds of formula I).

[0131]

Chemical formula

[0132] The compounds of formula A can be prepared according to the method described in WO2019 / 141980 and according to Scheme C. Reacting carboxylic acid D with a ketone, such as acetone or benzophenone (e.g., in the presence of TFA and TFAA), can afford ketal E. Compound A can be obtained by reaction of the anion of amine F (e.g., the anion formed by deprotonating F with NaHMDS) under suitable conditions (e.g., THF at - 40 °C to 0 °C).

[0133]

Chemical formula

[0134] Several routes to amine F can be envisioned. Some of these are shown in Schemes D - H. Aminobromide G can be converted to thiourea H (e.g., using benzoyl chloride, NH4SCN, Br2 in refluxing acetone, followed by refluxing 10% aqueous NaOH), which can then be converted to amine F, for example, using CuI, Cs2CO3, 1,10 - phenanthroline in refluxing dioxane.

[0135]

Chem.

[0136] Thiourea J can be converted to amine F, for example, using Br2 in CHCl3 from 0 °C to reflux, or using Br2, AcOH, and LiBr.

[0137]

Chem.

[0138] Thiocyanate K can be converted to amine F, for example, using H2, Pd / C in acetic acid at room temperature, or using Fe / AcOH at room temperature.

[0139]

Chem.

[0140] Bicyclic L can be aminated to form amine F, for example, using tBu2Zn(TMP)Li, THF at room temperature, followed by copper cyanide and BnONH2 at room temperature.

[0141]

Chem.

[0142] Aminothiol M can be reacted with compound N, for example, in refluxing THF, to form amine F.

[0143] [Chemical formula]

[0144] The amine of formula R, which is a subset of amine F (where x is an integer from 0 to 5), can be formed according to Scheme I. Ether Q can be obtained by the reaction of nitrof luoro compound O and phenol P in the presence of a base (e.g., K2CO3 or NaH in DMF). Reduction (e.g., by Pd / C and H2 in ethanol at room temperature, or by Fe and NH4Cl in THF / methanol at 60 °C), followed by reaction with KSCN or NaSCN (e.g., in the presence of Br2 in AcOH or methanol at 0 °C to room temperature), can give amine R (a subset of amine F).

[0145] [Chemical formula] [Examples]

[0146] General method Flash chromatography was performed using a Biotage (registered trademark) SNAP KP-Sil cartridge filled with 50 μm silica particles having a surface area of 500 m 2 / g, or Biotage Isolera 4 using an alternative cartridge (e.g., Puriflash manufactured by Interchim) if described, or using silica gel (40 - 63 μm particles). Visualization was carried out using UV light (254 nm) and staining with either potassium permanganate, phosphomolybdic acid (PMA), or ninhydrin solution.

[0147] All 1 1H NMR spectra were acquired on a Bruker AVIII 400 equipped with a 5 mm QNP, or a Bruker AVI 500 equipped with a 5 mm QNP. Chemical shifts are expressed in parts per million (δ) with the solvent as the reference. Coupling constants J are expressed in Hertz (Hz).

[0148] MS was performed on a Waters Alliance ZQ MS using a YMC-Triart C18 50×2 mm, 5 micron LC column, either by Method A (solvent: acetonitrile gradient of 5 - 90% in water (containing 1 volume % of 28 (mass) % aqueous ammonia solution)) or by Method B (solvent: acetonitrile gradient of 5 - 90% in water (containing 1% formic acid)). Flow rate: 0.8 mL / min. Wavelengths were 254 and 210 nm.

[0149] Method A (basic pH for 5 minutes) Column: YMC-Triart C18 50×2 mm, 5 μm. Flow rate: 0.8 mL / min. Injection volume: 5 μL. Mobile phase A H2O B CH3CN C 50%H2O / 50%CH3CN + 1.0% ammonia (aqueous solution)

[0150]

Table 1

[0151] Method B (acidic pH for 5 minutes) Column: YMC-Triart C18 50×2 mm, 5 μm. Flow rate: 0.8 mL / min. Injection volume: 5 μL. Mobile phase A H2O B CH3CN C 50%H2O / 50%CH3CN + 1.0% formic acid

[0152]

Table 2

[0153] Alternatively, MS was performed on a Waters Acquity UPLC-QDA UV-MS system using Method C (high pH) or Method D (low pH):

[0154] Method C (basic pH for 3.5 minutes)

[0155] [Table 3]

[0156] Method D (acidic pH for 3.5 minutes)

[0157] [Table 4]

[0158] All reagents were obtained from commercial suppliers and used as received unless otherwise stated.

[0159] All compounds were named using ChemBioDraw Ultra 14.0.

[0160] Intermediate A: 2-chloro-1-(2-chlorophenoxy)-4-nitrobenzene

[0161] [Chemical Structure]

[0162] 3-Chloro-4-fluoronitrobenzene (4.0 g, 23 mmol) and 2-chlorophenol (2.36 mL, 22.8 mmol) were dissolved in DMF (10 mL). Potassium carbonate (3.15 g, 22.8 mmol) was added and the reaction mixture was heated at 80 °C for 48 h. The suspension was cooled to room temperature and water was added. The mixture was extracted with EtOAc, the combined extracts were dried (MgSO4) and evaporated in vacuo to give the title compound as a yellow solid (6.47 g, quantitative). 1 H NMR δ H (500 MHz, DMSO-d 6) 8.48 (d, J = 2.8 Hz, 1H), 8.17 (dd, J = 9.1, 2.8 Hz, 1H), 7.70 (dd, J = 8.3, 1.6 Hz, 1H), 7.55 - 7.46 (m, 1H), 7.40 (ddd, J = 8.3, 6.7, 1.6 Hz, 2H), 6.89 (d, J = 9.1 Hz, 1H).

[0163] Intermediates B - I: The following intermediates were prepared from commercially available substances using the general method described for Intermediate A.

[0164]

Table 5A

[0165]

Table 5B

[0166] Intermediate J: 2 - Chloro - N - methyl - N - (4 - nitrophenyl)aniline

[0167]

Chemical formula

[0168] Sodium hydride (60% in mineral oil) (198 mg, 4.96 mmol) was suspended in DMF (5 mL) under nitrogen and cooled to 0 °C. 2 - Chloro - N - methylamine (0.436 g, 3.54 mmol) was added, followed by 4 - fluoronitrobenzene (0.50 g, 3.54 mmol) in DMF (5 mL). The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was added to water (ca. 25 mL), the suspension was stirred for 15 min, and filtered. The solid was washed with water and dried under vacuum to give the title compound as an orange solid (1.13 g, quantitative). 1 H NMR δ H(500 MHz, CDCl3) 8.11 (d, J = 9.5 Hz, 2H), 7.58 (dd, J = 7.6, 1.9 Hz, 1H), 7.45 - 7.30 (m, 3H), 6.52 (d, J = 9.1 Hz, 2H), 3.38 (s, 3H); LCMS (Method A): 3.65 min (263.1, MH + ).

[0169] Intermediates K - P: The following intermediates were prepared from commercially available substances using the general method described for Intermediate J.

[0170]

Table 6A

[0171]

Table 6B

[0172] Intermediate Q: 2-(Cyclopropylmethoxy)phenol

[0173]

Chem.

[0174] A solution of 1,2-dihydroxybenzene (5.0 g, 45.4 mmol) in DMF (20 mL) was treated with potassium carbonate (7.53 g, 54.5 mmol) and (bromomethyl)cyclopropane (4.40 mL, 45.4 mmol) and stirred at 60 °C overnight. The reaction was cooled to room temperature, then quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and concentrated under reduced pressure to give an oil. The residue was purified by chromatography (SiO2, 0 - 5% EtOAc in PE) to give the title compound as a pale yellow oil (2.2 g, 30%). 1 H NMR δ H(500 MHz, CDCl3) δ 6.96 - 6.92 (m, 1H), 6.92 - 6.80 (m, 3H), 5.78 (s, 1H), 3.87 (d, J = 7.1 Hz, 2H), 1.36 - 1.22 (m, 1H), 0.70 - 0.60 (m, 2H), 0.35 (q, J = 5.2 Hz, 2H); LCMS (Method B): 2.54 min, not ionized

[0175] Intermediate R: 5-Chloro-N-methyl-N-(4-nitrophenyl)pyridin-3-amine

[0176]

Chem.

[0177] A solution of Intermediate L (754 mg, 3.02 mmol) in THF (10 mL) was treated with sodium hydride (60% in mineral oil) (145 mg, 3.62 mmol) under ice-cooling. The reaction mixture was stirred for 15 min, then iodomethane (0.282 mL, 4.53 mmol) was added. The reaction mixture was stirred at room temperature for 2 h, then quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and concentrated under reduced pressure to give the title compound as a red solid (773 mg, 97%). LCMS (Method A): 3.10 min (264.1, MH + +).

[0178] Intermediate S: 3-Chloro-4-(2-chlorophenoxy)aniline

[0179]

Chem.

[0180] Intermediate A (6.47 g, 23.5 mmol) was dissolved in EtOH (20 mL). A saturated aqueous solution of ammonium chloride (5 mL) was added to the reaction mixture together with iron (6.65 g, 117 mmol). The reaction mixture was heated at 80 °C for 18 h. After cooling to room temperature, the mixture was filtered through dicalite (registered trademark), washed with EtOAc, and the filtrate was concentrated under reduced pressure. The residue was partitioned between water and DCM. The organic extract was dried (MgSO4) and concentrated under reduced pressure to give the title compound as a brown solid (5.37 g, 90%). 1 H NMR δ H (500 MHz, DMSO-d 6 ) 7.51 (dd, J = 7.9, 1.5 Hz, 1H), 7.26 - 7.20 (m, 1H), 7.04 (td, J = 7.9, 1.4 Hz, 1H), 6.91 (d, J = 8.7 Hz, 1H), 6.74 (d, J = 2.6 Hz, 1H), 6.61 (dd, J = 8.3, 1.4 Hz, 1H), 6.57 (dd, J = 8.7, 2.6 Hz, 1H), 5.38 (s, 2H); LCMS (Method A): 3.35 min (254.0, MH + ).

[0181] Intermediates T - AH: The following intermediates were prepared from the appropriate intermediates using the general method described for Intermediate S.

[0182]

Table 7A

[0183]

Table 7B

[0184]

Table 7C

[0185]

Table 7D

[0186] Intermediate AI: N6-(2-Chlorophenyl)-N6-methylbenzo[d]thiazole-2,6-diamine

[0187]

Chem.

[0188] Sodium thiocyanate (575 mg, 7.09 mmol) was dissolved in MeOH (10 mL) and cooled to 0 °C. Bromine (0.219 mL, 4.25 mmol) was added dropwise and the reaction mixture was stirred for 5 minutes. Intermediate Y (825 mg, 3.55 mmol) in MeOH (10 mL) was added and the reaction mixture was warmed to room temperature and stirred for 48 hours. The reaction mixture was concentrated under reduced pressure and partitioned between DCM and saturated aqueous NaHCO3. The aqueous layer was further extracted with DCM, the combined organics were dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography (SiO2, 0 - 50% EtOAc in PE) to give the title compound as a grey foam (719 mg, 70%). 1 H NMR δ H (500 MHz, DMSO-d 6 ) 7.55 (dd, J = 8.0, 1.6 Hz, 1H), 7.43 - 7.38 (m, 1H), 7.34 (dd, J = 8.0, 1.6 Hz, 1H), 7.30 - 7.24 (m, 1H), 7.14 (d, J = 8.7 Hz, 3H), 6.98 (d, J = 2.5 Hz, 1H), 6.45 (dd, J = 8.7, 2.5 Hz, 1H), 3.19 (s, 3H); LCMS (Method A): 3.05 min (290.0 MH + ).

[0189] Intermediates AJ - AY: The following intermediates were prepared from the appropriate intermediates or commercially available materials using the general method described for Intermediate AI.

[0190]

Table 8A

[0191]

Table 8B

[0192]

Table 8C

[0193]

Table 8D

[0194] Intermediate AZ: N-(6-((2-Chlorophenyl)(methyl)amino)benzo[d]thiazol-2-yl)-3-hydroxy-4-methoxypicolinamide

[0195]

Chemical Structure

[0196] A mixture of Intermediate AI (250 mg, 0.863 mmol) and 8-methoxy-2,2-dimethyl-4H-[1,3]dioxino[5,4-b]pyridin-4-one 2,2,2-trifluoroacetate (418 mg, 1.29 mmol) was dissolved in DMF (3 mL). A solution of NaHMDS in THF (2 M) (2.16 mL, 4.31 mmol) was added, and the reaction mixture was stirred at room temperature for 7 days. The reaction was quenched with water and stirred for 30 minutes. The resulting solid was filtered, washed with water, slurried in EtOH, and dried under vacuum to give the title compound as a brown solid (224 mg, 59%). 1 H NMR δ H (500 MHz, DMSO-d 6) 7.63 (d, J = 4.6 Hz, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.49 - 7.36 (m, 3H), 7.35 - 7.28 (m, 1H), 7.15 (d, J = 2.2 Hz, 1H), 6.74 (d, J = 4.7 Hz, 1H), 6.54 (dd, J = 8.8, 2.3 Hz, 1H), 3.76 (s, 3H), 3.25 (s, 3H). NH / OH was not observed; LCMS (Method A): 1.88 min (441.0, MH + ).

[0197] Intermediates BA - BP: The following intermediates were prepared from the appropriate intermediates using the general method described for Intermediate AZ.

[0198]

Table 9A

[0199]

Table 9B

[0200]

Table 9C

[0201]

Table 9D

[0202]

Table 9E

[0203] (Example 1) 3-(6-(2-Chloro-4-fluorophenoxy)benzo[d]thiazol-2-yl)-8-methoxy-2H-pyrido[2,3-e][1,3]oxazine-2,4(3H)-dione

[0204]

Chem.

[0205] Triphosgene (53.2 mg, 0.179 mmol) was added to a solution of N-(6-(2-chloro-4-fluorophenoxy)benzo[d]thiazol-2-yl)-3-hydroxy-4-methoxypicolinamide (40 mg, 0.09 mmol) in DCM (1.5 mL). Pyridine (0.109 mL, 1.35 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was purified by column chromatography (SiO2, 0 - 100% EtOAc in PE) to isolate the title compound as a yellow gum (10 mg, 25%). 1 1H NMR δ H (500 MHz, DMSO-d 6 ) 8.58 (d, J = 5.4 Hz, 1H), 8.10 (d, J = 8.9 Hz, 1H), 7.75 - 7.69 (m, 2H), 7.59 (d, J = 5.5 Hz, 1H), 7.38 (d, J = 5.3 Hz, 1H), 7.33 - 7.29 (m, 2H), 4.06 (s, 3H); LCMS (Method B): 3.72 min (472.1, MH + ).

[0206] (Examples 2 - 5) The following examples were prepared using the general method described in Example 1 from the appropriate intermediates (preparation described above or in WO2019 / 141980).

[0207]

Table 10A

[0208]

Table 10B

[0209] (Example 6) 3-(6-(2-Chloro-4-fluorophenoxy)benzo[d]thiazol-2-yl)-8-methoxy-2-thioxo-2,3-dihydro-4H-pyrido[2,3-e][1,3]oxazin-4-one

[0210]

Chemical Structure

[0211] Thiophosgene (20.6 mg, 0.179 mmol) was added to a solution of N-(6-(2-chloro-4-fluorophenoxy)benzo[d]thiazol-2-yl)-3-hydroxy-4-methoxypicolinamide (40 mg, 0.09 mmol) in DCM (1 mL). Pyridine (0.109 mL, 1.35 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was purified by column chromatography (SiO2, 0 - 100% EtOAc in PE) to isolate the title compound as a pale orange solid (22 mg, 50%). 1 H NMR δ H (500 MHz, DMSO-d 6 ) 8.61 (d, J = 5.4 Hz, 1H), 8.09 (d, J = 8.8 Hz, 1H), 7.74 - 7.69 (m, 2H), 7.62 (d, J = 5.5 Hz, 1H), 7.40 (dd, J = 9.1, 5.3 Hz, 1H), 7.37 - 7.31 (m, 1H), 7.30 (dd, J = 8.9, 2.6 Hz, 1H), 4.09 (s, 3H); LCMS (Method B): 4.05 min (488.1, MH + ).

[0212] (Examples 7 - 50) The following examples were prepared from the appropriate intermediates using the general method described in Example 6 (preparation described above or in WO / 2019 / 141980).

[0213]

Table 11A

[0214]

Table 11B

[0215]

Table 11C

[0216]

Table 11D

[0217]

Table 11E

[0218]

Table 11F

[0219]

Table 11G

[0220]

Table 11H

[0221]

Table 11I

[0222]

Table 11J

[0223]

Table 11K

[0224]

Table 11L

[0225]

Table 11M

[0226]

Table 11N

[0227]

Table 11O

[0228] (Example 51) To test the fungicidal activity of the compounds of the present invention The compounds were screened in 96-well plates using 10 compounds per plate. Each compound was screened using agar amended with test substances at 20, 2, 0.2, and 0.02 ppm. 50 and 10 ppm of proline and 0.2% DMSO were used as positive and negative controls, respectively. Each test concentration and standard was tested twice on the plate.

[0229] The compounds were screened against the following three fungal pathogens - Botrytis cinerea, Alternaria alternata, and Zymoseptoria tritici. The agar used in the test was changed according to the pathogen, medium N was used for B. cinerea and A. alternata, and 1% potato dextrose agar was used for Z. tritici. For each pathogen, sufficient spores were added to the appropriate agar to obtain agar with 1,000 spores / mL of A. alternata, 5,000 spores / ml of B. cinerea, and 10,000 spores / mL of Z. tritici.

[0230] A 10× stock solution in 2% DMSO was generated for each dosage, i.e., 200, 20, 2, and 0.2 ppm, and 10 μl of this was added to the appropriate wells on the plate. Equal volumes of 2% DMSO and 500 and 100 ppm proline stock were added as controls. To each well, 90 μl of the appropriate agar spore suspension was added to obtain the final well concentrations outlined in the first paragraph.

[0231] The plates were incubated at room temperature (18 °C), a) for A. alternata and B. cinerea after 3 - 4 days b) for Z. tritici after 7 days and were evaluated.

[0232] The amount of fungal growth in each well was compared to the DMSO control and scored according to the following legend: A - EC50 < 2 ppm B - 2 ≤ EC50 < 20 C - EC50 ≥ 20 D - No activity detected at the maximum dosage tested NT - Not tested

[0233] The ranking in the table is as follows:

[0234]

Table 12A

[0235]

Table 12B

Claims

1. A compound of formula I, or an agriculturally acceptable salt or N-oxide thereof: 【Chemical 1】 [wherein, X 1 and X 2 are each independently selected from carbon and nitrogen; Y 1 is independently selected from O and S; =Y 2 is independently selected from =O and =S; Z 1 is, independently, absent, or selected from C(O)O, OC(O), O, S, S(O), S(O) 2 , C(O), C 1 ~C 3 -alkylene and N(C1-C4-alkyl); R1, independently at each occurrence, is selected from C 1 ~C4-alkyl, halogen, and OR9; R 2 is, independently at each occurrence, cyano, nitro, C 1 to C4-alkyl, halogen, OR 9 , and phenyl optionally substituted with from 1 to 5 R 12 groups; R 3 is, independently at each occurrence, C 3 to C 8 -alkyl and C 0 to C 3 -alkylene-R 3a selected from; wherein R 3a is, independently at each occurrence, phenyl, 5- or 6-membered heteroaryl, 5-, 6-, 7- or 8-membered heterocycloalkyl and C 3 to C 8 -cycloalkyl selected from; said heterocycloalkyl or cycloalkyl group is monocyclic or bicyclic; said heteroaryl or phenyl group may optionally be substituted with 1 to 5 R 12 groups, or said heterocycloalkyl or cycloalkyl group may optionally be substituted with 1 to 4 R 13 groups; R 4 is, independently at each occurrence, C 1 to C 6 -alkyl, C 3 to C 6 -cycloalkyl and C 1 to C 6 -haloalkyl; R 10 is, independently at each occurrence, selected from H, C 3 to C 6 -cycloalkyl, C 1 to C 6 -alkyl and benzyl; R 9 is, independently at each occurrence, H, C 1 to C 6 -alkyl, C 0 to C 3 -alkylene-C 3 to C 6 -cycloalkyl, C(O)-C 1 to C 6 -alkyl and C 1 to C 6 -haloalkyl; R 12 is, in each occurrence, independently selected from cyano, nitro, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, halogen, SR 10, and OR 9; R 13 is, independently at each occurrence, =O, =S, C 1 to C 6 -alkyl, C 1 to C 6 -haloalkyl, C 3 to C 6 -cycloalkyl; halogen, nitro, OR 9 , SR 10 and selected from cyano; y is an integer independently selected from 0, 1, and 2; m is an integer independently selected from 0, 1, 2, and 3; Here, any of the aforementioned alkyl, alkylene, alkenyl, cycloalkyl, heterocycloalkyl, and benzyl may, when chemically possible, be substituted with one to four substituents independently selected in each occurrence from the group consisting of =O; =NR a 、=NOR a 、C 1 ~C 4 -alkyl, halo, nitro, cyano, C 1 ~C 4 -haloalkyl, C 2 ~C 4 -alkenyl, C 2 ~C 4 -alkynyl, NR a R b 、S(O) 2 R a 、S(O)R a 、S(O)(NR a )R a 、S(O) 2 NR a R a 、CO 2 R a 、C(O)R a 、CONR a R a 、OR a and SR a and may be optionally substituted by one to four substituents independently selected in each occurrence from the group consisting of; Here, R a is independently selected from H and C 1 ~C 4 -alkyl; R b is independently H, C 1 ~C 4 -alkyl, C(O)-C 1 ~C 4 -alkyl, or S(O) 2 -C 1 ~C 4 -alkyl].

2. R 4 is independently C 1 to C 6 -alkyl and C 3 to C 6 -cycloalkyl, and the compound according to claim 1

3. The compound according to claim 1 or 2, wherein y is 0.

4. Y 1 The compound according to any one of claims 1 to 3, wherein Y is O.

5. =Y 2 The compound according to any one of claims 1 to 4, wherein =S is =S.

6. X 1 The compound according to any one of claims 1 to 5, wherein 1 is carbon.

7. X 2 The compound according to claim 6, wherein 2 is carbon.

8. X 2 The compound according to claim 6, wherein 2 is nitrogen.

9. Z 1 is, independently at each occurrence, O, S, C 1 -alkylene and NR 5 selected from, where R 5 is C 1 to C 3 -alkyl, a compound according to any one of claims 1 to 8.

10. Z 1 The compound according to claim 9, wherein Z is O.

11. R 3 is R 3a The compound according to any one of claims 1 to 10, which is

12. R 3a The compound according to any one of claims 1 to 11, wherein R is phenyl which may optionally be substituted.

13. R 3 is C 3 to C 8 -alkyl, a compound according to any one of claims 1 to 10.

14. The compound according to any one of claims 1 to 13, wherein m is 0.

15. The compound of formula (I) is ​ 【Chemical 2B】 【Chemical 2C】 【Chemical 2D】 【Chemical 2E】 selected from

16. A method for controlling a fungal disease, comprising applying an agriculturally effective and substantially non-phytotoxic amount of the compound according to any one of claims 1 to 15 to plant seeds, the plants themselves, or the area where the plants are intended to grow.

17. Use of the compound according to any one of claims 1 to 15 for controlling a fungal disease of plants.

18. A fungicidal composition comprising an effective and non-phytotoxic amount of the active compound according to any one of claims 1 to 15.

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