GB2587787A - Agricultural chemicals - Google Patents

Abstract

A compound of formula (I), or an agronomically acceptable salt or N-oxide thereof: wherein a single one of X1 and X2 is S and a single one of X1 and X2 is N; Y1 is independently selected from O and S; R1, R5 and R15 are each independently a substituent; R2 and R3 are each independently selected from: H and a substituent; R4 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, C1-C6-alkyl and benzyl; or R3 and R4 together form a group independently selected from C1-C2-alkylene, -C(O)- and -C(S)-; R6 is a substituent; n is independently an integer selected from 0, 1 and 2; m is independently an integer selected from 0, 1, 2 and 3. The compounds of formula (I) are useful in the treatment of fungal diseases in plants. Preferably, Y1 is O, R2 is Me, R3 is H or acetyl, R4 is H and R6 is 4-fluorophenyloxy, 4-fluorophenylthio or 4-fluorophenyl-N-methylamino; or Y1 is O, R2 is Me, R6 is 4-fluorophenylthio or 4-fluorophenyl-N-methylamino, and R3 and R4 together form -C(S)-.

Description

Agricultural Chemicals The present invention relates to picolinic acid derivatives that are useful in treating fungal disease.

Given the global increase in demand for food, there is an international need for new treatments to reduce food crop losses to disease, insects and weeds. Over 40% of crops are lost before harvest, and 10% post harvest, worldwide. Losses have actually increased since the mid-1990s.

A new threat contributing to this is the emergence of chemical-resistant organisms, for example, glyphosate-resistant weeds in the USA and strobilurin-resistant strains of septoria fungal species.

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

Certain picolinic acid derivatives are shown to be useful in treating fungal disease in PCT/GB2019/050111 and GB1900696.4 (both unpublished).

An aim of certain embodiments of the present invention is to provide pesticides (e.g. fungicides) which have activity either non-selectively, i.e. broad spectrum activity, or which are active specifically against selective target organisms.

An aim of certain embodiments of the present invention is to provide compounds which are less persistent in the environment after use than prior art compounds. Alternatively or additionally, the compounds of the present invention may be less prone to bioaccumulafion

once in the food chain than prior art compounds.

Another aim of certain embodiments of the invention is to provide compounds which are less harmful to humans than prior art compounds. Alternatively or additionally, the compounds of the invention may be less harmful than prior art compounds to one or more of the following groups: amphibians, fish, mammals (including domesticated 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.

The compounds of the invention may be as active as or more active than prior art compounds. They may have activity against organisms which have developed a resistance to prior art compounds. However, the present invention may also concern compounds which have a lower or similar level of activity relative to that of the prior art compounds. These lower activity compounds are still effective as fungicides but may have other advantages relative to existing compounds such as, for example, a reduced environmental impact.

The compounds of the invention may be more selective than prior art compounds, i.e. they may have better, similar or even slightly lower activity than prior art compounds against target species but have a significantly lower activity against non-target species (e.g. the crops which are being protected).

Certain embodiments of the invention provide compounds that achieve one or more of the above aims. The compounds may be active in their own right or may metabolise or react in aqueous media to yield an active compound.

Summary of the Invention

In a first aspect of the invention is provided a compound of formula I, or an agronomically acceptable salt or N-oxide thereof: R20 OR3 R4 (R5)m (R)n N(y1 Rei wherein a single one of X1 and X2 is S and a single one of X1 and X2 is N; Y1 is independently selected from 0 and S; 21 is independently absent or is CR8R9; Z2 is independently absent or is selected from C(0)0, OC(0), 0, S, S(0), 5(0)2, C(0)N1R7, NIR7C(0), S(0)2N1R7, NIR7S(0)2, S(0)NIR7, NIR7S(0), CIR51R5, CIR5R50, CIR51R5NR7, C(0), C(S), C=NOR15 and NW; R1, R5 and R15 are each independently at each occurrence selected from Ci-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, halogen, nitro, OR11, SR12, OS(0)2R12, S(0)2R12, C(0)0R12, C(0)NR12R12, C(0)R12, S(0)2NR12R12, S(0)(NR12)R12, S(0)R12, cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR121R13; R2 and R3 are each independently selected from: H, C3-C6-cycloalkyl, C(0)R14, C(0)0R14, CH20C(0)R14 and CH20C(0)0R14; R4 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, Ci-C6-alkyl and benzyl; or IR2 and R4 together form a group independently selected from C1-C2-alkylene, -C(0)-and -C(S)- R6 is selected from R5 and -Z1-Z2-R64; wherein R64 is selected from Cs-Ca-alkyl and Co-C3-alkylene-R69; wherein R69 is independently at each occurrence selected from phenyl, 5-or 6-membered heteroaryl, 5-, 6-, 7-or 8-membered heterocycloalkyl and Cs-Ca-cycloalkyl; said heterocycloalkyl or cycloalkyl group being monocyclic or bicyclic; said heteroaryl or phenyl group being optionally substituted with from 1 to 5 R18 groups or said heterocycloalkyl or cycloalkyl group being optionally substituted with from 1 to 4 R16 groups; Z1 is independently absent or is CIR8R9; Z2 is independently absent or is selected from C(0)0, OC(0), 0, S, 5(0), 5(0)2, C(0)NR', NR7C(0), S(0)2NR7, NR7S(0)2, S(0)NIR7, NR7S(0), CR8R9, CR8R90, CR8R9NR7, C(0), C(S), C=NOR19 and NIR7; R18 is independently at each occurrence selected from: =0, =S, C1C6-haloalkyl, C3-C6-cycloalkyl; halogen, nitro, OR11, 5R12, OS(0)2R12, S(0)2R12, S(0)2NR12R12, S(0)(NR12)R12, S(0)R12, cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NIR12R12; R7 and R12 are each independently at each occurrence selected from: H, C3-C6-cycloalkyl, CiC6-alkyl and benzyl; or where two R12 groups are attached to the same nitrogen atom, said IR12 groups, together with said nitrogen atom form a 4-, 5-, 6-or 7-membered heterocycloalkyl ring; R8 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, Ci-C6-alkyl, phenyl and 5-or 6-membered heteroaryl; R9 is independently at each occurrence selected from: H, halo and OR16; or R8 and R9 together with the carbon atom to which they are attached may form a C3-C6-cycloalkyl ring or a 3-, 4-, 5-or 6-membered heterocycloalkyl ring; R19 is each independently at each occurrence selected from: H, Ca-C6-cycloalkyl, and Ci-C3-alkylene-R164; wherein R194 is independently at each occurrence selected from phenyl and 5-or 6-membered heteroaryl; R11 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, C(0)-C1-C6-alkyl and Ci-C6-haloalkyl; R13 is independently at each occurrence selected from; H, C(0)-Ci-C6-alkyl and S(0)2-C1-C6-alkyl; or where an R12 group and an R13 group are attached to the same nitrogen atom, said R12 and R13 groups, together with said nitrogen atom form a 4-, 5-, 6-or 7-membered heterocycloalkyl ring; R14 is independently at each occurrence selected from: Ci-C6-alkyl, phenyl, benzyl and 03-C6-cycloalkyl n is independently an integer selected from 0, 1 and 2, m is independently an integer selected from 0, 1, 2 and 3; and wherein any aforementioned alkyl, alkylene, alkenyl, cycloalkyl (including where an R8 and an R9 group together with an atom to which they are attached form a cycloalkyl ring), heterocycloalkyl (including where two R12 groups or an R12 group and an R13 group or an R8 and an IR9 group together with an atom to which they are attached form a heterocycloalkyl ring), alkynyl, C(0)-alkyl, S(0)2-alkyl and benzyl is optionally substituted, where chemically possible, by 1 to 4 substituents which are each independently selected at each occurrence from the group consisting of: =0; =NRa, =NORa, C1-C4-alkyl, halo, nitro, cyano, Cl-C4-haloalkyl, C2-C4-alkenyl, C2C4-alkynyl, NRaRb, S(0)2R8, S(0)R8, S(0)(NRa)Ra, S(0)2NRaR8, CO2Ra, C(0)R8, CONRaRa, ORa and SRa; wherein Ra is independently selected from H and Ci-04-alkyl; and IR9 is independently selected from H, Ci-C4-alkyl, C(0)-C1-04-alkyl and S(0)2-CrC4-alkyl.

In certain embodiments, the compound of formula I is a compound of formula II: R20 OR3 R4 (R5)m (R1)n -N yl Reb II wherein R1, R2, R3, R4, IR5, n, m, X1, X2, Z2 and Re9 are as described above for formula I. It may be that Z2 is selected from 0, S and NW.

In certain embodiments, the compound of formula I is a compound of formula III: wherein R1, R2, R3, R4, R5, n, m, X1, X2, Z2 and R15 are as described above for formula I, and x is an integer selected from 0, 1, 2, 3, 4 and 5. It may be that Z2 is selected from 0, S and NR7.

In certain embodiments, the compound of formula I is a compound of formula IV: (R5)m

R

wherein R1, R2, R3, R4, R5, n, m, and R6 are as described above for formula I. wherein R1, R2, R3, R4, R5, n, m, and R6 are as described above for formula I. In certain embodiments, the compound of formula I is a compound of formula VI: (R5)m R20 OR3 R4 Ni (R1)n -N wherein R1, R2, R3, R4, R5, n, m, Z2 and R65 are as described above for formula I. It may be that Z2 is selected from 0, S and NR7.

In certain embodiments, the compound of formula I is a compound of formula VII: In certain embodiments, the compound of formula I is a compound of formula V: (R5)m R20 yl _R6b

VII

wherein R1, R2, R3, R4, R5, n, m, Z2 and R66 are as described above for formula I. It may be that Z2 is selected from 0, S and NR'.

)n -N Y1 (R15)x VIII In certain embodiments, the compound of formula I is a compound of formula VIII: (R5)m R20 OR3 R4 c <NI wherein R1, R2, R2, R4, R5, n, m, Z2 and R16 are as described above for formula I; and x is an integer selected from 0, 1,2, 3,4 and 5. It may be that Z2 is selected from 0, S and NIR7.

In certain embodiments, the compound of formula I is a compound of formula IX: (R5)m R20 OR3 R4 (NI wherein R1, R2, R3, R4, R5, n, m, Z2 and R15 are as described above for formula I; and x is an integer selected from 0, 1,2, 3,4 and 5. It may be that Z2 is selected from 0,S and NR7. In certain embodiments, the compound of formula I is a compound of formula X: (R5)m R20 OR3a

HN yl

(R1)n -N wherein R1, R2, R5, n, m, X1, X2 and R6 are as described above for formula I; and R3a is independently selected from: H, Ci-C4-alkyl, C3-C6-cycloalkyl, C(0)R14, C(0)0R14, CH20C(0)R14 and CH200(0)0R14.

In certain embodiments, the compound of formula I is a compound of formula XI: )n -N yl S Z

IX

(R15)x wherein R1, R2, R5, n, m, X1, X2 and R6 are as described above for formula I; and Y2 is independently selected from 0 and S. wherein R1, R2, R3, R4, R5, n, m, X1, X2, r and IR66 are as described above for formula I; and R" is independently selected from: H, C1-C4-alkyl, C3-C6-cycloalkyl, C(0)R14, C(0)0R14, CH20C(0)R14 and CI-120C(0)0R14. It may be that 72 is selected from 0, S and NW.

In certain embodiments, the compound of formula I is a compound of formula XIII: In certain embodiments, the compound of formula I is a compound of formula XII: (R5)m R20 OR" y2 (R5)m Rab y 1 X1 Z2' XIII wherein R1, R2, R5, n, m, X1, X2, 72 and R66 are as described above for formula I; and Y2 is independently selected from 0 and S. It may be that Z2 is selected from 0, S and NW.

wherein R1, R2, R5, n, m, X1, X2, Z2 and R15 are as described above for formula I; R3a is independently selected from: H, Ci-C4-alkyl, C3-C6-cycloalkyl, C(0)R14, C(0)0R14, R2o In certain embodiments, the compound of formula I is a compound of formula XIV: (R5)m (W)n CH20C(0)R14 and CH200(0)0R14; and x is an integer selected from 0, 1, 2, 3, 4 and 5. It may be that Z2 is selected from 0, S and NIR7.

In certain embodiments, the compound of formula I is a compound of formula XV: wherein R1, rc ^2, R5, n, m, X1, X2, Z2 and R15 are as described above for formula I; Y2 is independently selected from 0 and S; and x is an integer selected from 0, 1, 2, 3, 4 and 5. It may be that Z2 is selected from 0, S and NIR7.

The following embodiments apply to compounds of any of formulae (I)-(XV). These embodiments are independent and interchangeable. Any one embodiment may be combined with any other embodiment, where chemically allowed. In other words, any of the features described in the following embodiments may (where chemically allowable) be combined with the features described in one or more other embodiments. In particular, where a compound is exemplified or illustrated in this specification, any two or more of the embodiments listed below, expressed at any level of generality, which encompass that compound may be combined to provide a further embodiment which forms part of the present disclosure.

It may be that IR1 is independently at each occurrence selected from C1-C4-alkyl, halo and OR". It may be that n is 1 or 2. Preferably, however, it may be that n is 0.

R2 may be independently selected from H, C1-C4-alkyl and C3-C6-cycloalkyl. R2 may be independently selected from Ci-C4-alkyl and C3-C6-cycloalkyl. R2 may be methyl or ethyl R2 may be methyl.

IR' may be independently selected from H, C1-C4-alkyl, C3-C6-cycloalkyl, C(0)R14, C(0)0R14, CH20C(0)R14 and CH20C(0)0R14. IR' may be independently selected from H, C(0)R14, C(0)0R14, CH20C(0)R14 and CH20C(0)0R14. IR3 may be independently selected from H, and C(0)R14. IR3 may be H. IR3 may be C(0)R14, e.g. C(0)Me. y2

R20 0 ( (N )n'N y1 (R5), R4 may be selected from Ca-C6-cycloalkyl, C-C6-alkyl and benzyl. R4 may be Ci-04-alkyl, e.g. methyl. R4 may be H. It may be that R3 and 54 together form a group independently selected from C1-02-alkylene, -C(0)-and -C(S)-. It may be that R3 and R4 together form a group -C(=Y2)-; wherein Y2 is independently selected from 0 and S. y2 may be S. Y2 may be 0.

It may be that 53 and R4 together form a Ci-C2-alkylene. It may be that R3 and 54 together form a Ci alkylene, e.g. CH2 or CMe2 It may be that R3 and R4 together form a C2 alkylene, e.g. CH2CMe2, CMe2CH2 or 0H20H2.

Y1 may be S. Y1 may be O. m may be O. m may be 1.

R5 may be independently at each occurrence selected from. cyano, nitro, Ci-04-alkyl, halo and OR11.

It may be that X1 is S and X2 is N. It may be that X1 is N and X2 is S. R6 may be R5.

R6 may be Z1-Z2-R6.

Z1 may be CR6R6. Preferably, however, Z1 is absent. R6 may be Z2-R6a.

Z2 may independently be absent or selected from 0(0)0, 00(0), 0, S, S(0), S(0)2, Ci-Caalkylene and NR7. Z2 may be independently absent or selected from 0(0)0, 00(0), 0, S, CIR856, and NR7. Z2 may independently be selected from CR8R6, S, NR and 0. Z2 may independently be selected from NR7, S, and 0. Z2 may be selected from 0 and S Z2 may be 0. Z2 may be S. Z2 may be R7.

57 may be H. Preferably, however 57 is Ci-C4-alkyl, e.g. methyl. Z2 may be absent. 56 may be 56a.

R6a may be CH2R6b. Alternatively, 56a may be 56b.

56 may be zi_z2_566. R6 may be Z2-R6b. R6 may be 56b.

R65 may be optionally substituted phenyl, e.g. unsubstituted phenyl. R63 may be optionally substituted phenyl, e.g. unsubstituted phenyl 6b r< may have the structure: (R15)x wherein x is an integer selected from 0, 1, 2, 3, 4 and 5.

x may be at least 1. x may be 1, 2 or 3. x may be 1 or 2. x may be 1. x may be O. R15 may in a single occurrence be situated para to Z2. R.61) may have the structure: es (R15)y R wherein y is an integer selected from 0, 1,2, 3 and 4.

y may be at least 1. y may be 1 or 2. y may be 1. y may be O. R65 may have the structure: R15 R15 may be independently at each occurrence selected from: cyano, nitro, C1-C4-alkyl, Cl-C4-haloalkyl, halo, S-R12 and 0-R11. R15 may be independently at each occurrence selected from: C1-C4-alkyl, Ci-C4-haloalkyl and halo.

rc6b may be a 6-membered heteroaryl, e.g. a pyridine. Cl n6b

r< may have a structure selected from: L'n Cl CF3, Cl

F and

/-C F3 /5-...",...",/,...,...,,,,,...""..CI 1 1 Cl The compound of formula (I) may be selected from: Me0 OH

HN S ' b

-N

Me0 OH

S

-N

Me0 OH S '

HN -N b

Me0 OH S '

HN -N b

Me0 OH

S

-N

Me0 OH

S

-N

Me0 OAc

S

-N

Me0 OAc

S

-N

Me() OAc S 1-1KN N \O Me0 OAc

S

-N OMe

Detailed Description

The term Cni-Cn refers to a group with m to n carbon atoms.

The term "alkyl" refers to a linear or branched saturated monovalent hydrocarbon chain. For example, C1_C6-alkyl may refer to methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tett-butyl, n-pentyl and n-hexyl. The alkyl groups may be unsubstituted or substituted by one or more substituents. Specific subsfituents for each alkyl group independently may be fluorine, OR or NHIRa.

Me0 OAc

-N

Me() OAc (o

-N

HN OMe F and OMe

S

The term "alkylene" refers to a linear saturated divalent hydrocarbon chain. The alkylene groups may be unsubstituted or substituted by one or more substituents. Specific substituents for each alkylene group independently may be Ci-C4-alkyl, fluorine, ORa or N H Ra.

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

The term "alkenyl" refers to a branched or linear hydrocarbon group containing at least one double bond. The double bond(s) may be present as the E or Z isomer. The double bond may be at any possible position of the hydrocarbon chain; for example, "C2-C6-alkenyl" may refer to ethenyl, propenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl and hexadienyl. The alkenyl groups may be unsubstituted or substituted by one or more substituents. Specific substituents for any saturated carbon atom in each alkenyl group independently may be fluorine, ORa or NHRa.

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

The term "cycloalkyl" refers to a saturated hydrocarbon ring system containing, for example, 3, 4, 5 or 6 carbon atoms. For example, "C3-C6-cycloalkyl" may refer to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. The cycloalkyl groups may be unsubstituted or substituted by one or more substituents. Specific substituents for each cycloalkyl group independently may be fluorine, OR' or N H Ra.

The term heterocycloalkyl may refer to a monocyclic or bicyclic saturated or partially saturated group having the indicated number of atoms in the ring system and comprising 1 or 2 heteroatoms independently selected from 0, S and N in the ring system (in other words 1 or 2 of the atoms forming the ring system are selected from 0, S and N). By partially saturated it is meant that the ring may comprise one or two double bonds. This applies particularly to monocyclic rings with from 5 to 6 members. The double bond will typically be between two carbon atoms but may 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. A heterocycloalkyl group may be unsubstituted or substituted by one or more substituents. Specific substituents for any saturated carbon atom in each heterocycloalkyl group may independently be fluorine, OR' or NHIRa.

Aryl groups may be any aromatic carbocyclic ring system (i.e. a ring system containing 2(2n + 1)7 electrons). Aryl groups may have from 6 to 12 carbon atoms in the ring system. Aryl groups will typically be phenyl groups. Aryl groups may be naphthyl groups or biphenyl groups.

In any of the above aspects and embodiments, heteroaryl groups may be any aromatic (i.e. a ring system containing 2(2n + 1)7 electrons) 5-10 membered ring system comprising from 1 to 4 heteroatoms independently selected from 0, S and N On other words from 1 to 4 of the atoms forming the ring system are selected from 0, S and N). Thus, any heteroaryl groups may be independently selected from: 5 membered heteroaryl groups in which the heteroaromatic ring is substituted with 14 heteroatoms independently selected from 0, S and N; and 6-membered heteroaryl groups in which the heteroaromatic ring is substituted with 1-3 (e.g.1-2) nitrogen atoms; 9-membered bicyclic heteroaryl groups in which the heteroaromatic system is substituted with 1-4 heteroatoms independently selected from 0, S and N; 10- membered bicyclic heteroaryl groups in which the heteroaromatic system is substituted with 1- 4 nitrogen atoms. Specifically, heteroaryl groups may be independently 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, benzisoxazole, purine, quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline, pteridine, phthalazine, naphthyridine.

It may be that, in any group which is an aryl or heteroaryl group, that aryl or heteroaryl group is unsubstituted or is optionally substituted, where chemically possible, by 1 to 5 substituents which are each independently selected at each occurrence from: halo, nitro; cyano, NRalRa, NR'S(0)2Ra, NRaC(0)Ra, NIRaCONIRaRa, NIRaCO2Ra, OR', SRa, S(0)Ra, S(0)20Ra, S(0)2Ra, S(0)2NR3Ra,CO21R3 C(0)Ra, CONRaRa, cRbRbNRaRa, cRbRbona, Ci-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl and Cl-C4-haloalkyl; wherein IR and Rb are as described above for formulal.

Compounds of the invention containing one or more asymmetric carbon atoms can exist as two or more stereoisomers. Where a compound of the invention contains a double bond such as a C=C or C=N group, geometric cis/trans (or ZIE) isomers are possible. Where structural isomers are interconvertible via a low energy barrier, tautomeric isomerism ('tautomerism') can occur. This can take the form of proton tautomerism in compounds of the invention containing, for example, an imino, keto, or oxime group, or so-called valence tautomerism in compounds which contain an aromatic moiety. It follows that a single compound may exhibit more than one type of isomerism.

Included within the scope of the present invention are all stereoisomers, geometric isomers and tautomeric forms of the compounds of the invention, including compounds exhibiting more than one type of isomerism, and mixtures of one or more thereof.

The compounds of the invention may be obtained, stored and/or used in the form of an agronomically acceptable salt. Suitable salts include, but are not limited to, salts of acceptable inorganic acids such as hydrochloric, sulfuric; phosphoric, nitric, carbonic, boric, sulfamic, and hydrobromic acids, or salts of agronomically acceptable organic acids such as acetic, propionic, butyric, tartaric, maleic, hydroxymaleic, fumaric, malic, citric, lactic, mucic, gluconic, benzoic, succinic, oxalic, phenylacetic, methanesulfonic, toluenesulfonic, benzenesulfonic, salicylic, sulfanilic, aspartic, glutamic, edetic, stearic, palmitic, oleic, lauric, pantothenic, tannic, ascorbic and valeric acids. Suitable salts also include salts of inorganic and organic bases, e.g. counterions such as Na, Ca, K, Li, Mg, ammonium, trimethylsulfonium. The compounds may also be obtained, stored and/or used in the form of an N-oxide. Also included are acid addition salts or base salts wherein the counter ion is optically active; for example, d-lactate or 1-lysine, or racemic; for example, dl-tartrate or dl-arginine.

Cis/trans isomers may be separated by conventional techniques well known to those skilled in the art, for example, chromatography and fractional crystallisation.

Conventional techniques for the preparation/isolation of individual enantiomers when necessary include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC). Thus, chiral compounds of the invention (and chiral precursors thereof) may be obtained in enantiomerically-enriched form using chromatography, typically HPLO, on an asymmetric resin with a mobile phase consisting of a hydrocarbon, typically heptane or hexane, containing from 0 to 50% by volume of isopropanol, typically from 2% to 20%, and for specific examples, 0 to 5% by volume of an alkylamine e.g. 0.1% diethylamine. Concentration of the eluate affords the enriched mixture.

Alternatively, the racemate (or a racemic precursor) may be reacted with a suitable optically active compound, for example, an alcohol, or, in the case where the compound of the invention contains an acidic or basic moiety, a base or acid such as 1-phenylethylamine or tartaric acid. The resulting diastereomeric mixture may be separated by chromatography and/or fractional crystallisation and one or both of the diastereoisomers converted to the corresponding pure enantiomer(s) by means well known to a skilled person.

When any racemate crystallises, crystals of two different types are possible. The first type is the racemic compound (true racemate) referred to above wherein one homogeneous form of crystal is produced containing both enantiomers in equimolar amounts. The second type is the racemic mixture or conglomerate wherein two forms of crystal are produced in equimolar amounts each comprising a single enantiomer.

While both of the crystal forms present in a racemic mixture have identical physical properties, they may have different physical properties compared to the true racemate. Racemic mixtures may be separated by conventional techniques known to those skilled in the art -see for example, "Stereochemistry of Organic Compounds" by E. L. Elie! and S. H. Wilen (Wiley, 1994).

The activity of the compounds of the present invention can be assessed by a variety of in silico, in vitro and in vivo assays. In silico analysis of a variety of compounds has been demonstrated to be predictive of ultimate in vitro and even in vivo activity.

The present invention also includes all environmentally acceptable isotopically-labelled compounds of formulae Ito XV and their syntheses, wherein one or more atoms are replaced by atoms having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature.

Examples of isotopes suitable for inclusion in the compounds of the invention include isotopes of hydrogen, such as 2H and 3H, carbon, such as 11-u, 13C and 14C, chlorine, such as 'CI, fluorine, such as 18F, iodine, such as 1231 and 1251, nitrogen, such as 13N and 15N, oxygen, such as '50, 170 and 180, phosphorus, such as 32P, and sulfur, such as 35S.

Isotopically-labelled compounds can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described using an appropriate isotopically-labelled reagent in place of the non-labelled reagent previously employed.

Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of the words, for example "comprising" and "comprises", means "including but not limited to", and is not intended to (and does not) exclude other moieties, additives, components, integers or steps.

Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith.

If appropriate, the compounds of the invention can, at certain concentrations or application rates, be used as fungicides.

According to another aspect of the present invention, there is provided a method for controlling fungal diseases, the method comprising the application of an agronomically effective and substantially non-phytotoxic (to the crop plant) quantity of a compound of the invention to the seeds of the plants, to the plants themselves or to the area where it is intended that the plants will grow.

The pesticide may be applied as a seed treatment, foliar application, stem application, drench or drip application (chemigation) to the seed, the plant or to the fruit of the plant or to soil or to inert substrate (e.g. inorganic substrates like sand, rockwool, glasswool; expanded minerals like perlite, vermiculite, zeolite or expanded clay), Pumbe, Pyroclastic materials or stuff, synthetic organic substrates (e.g. polyurethane) organic substrates (e.g. peat, composts, tree waste products like coir, wood fibre or chips, tree bark) or to a liquid substrate (e.g. floating hydroponic systems, Nutrient Film Technique, Aeroponics).

In a further aspect, the present 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.

The term "effective and non-phytotoxic amount" means an amount of pesticide according to the invention which is sufficient to control or destroy any of the targeted pests present or liable to appear in the crops and which does not have any significant detrimental effect on the crops or indeed has a positive effect on plant vigour and yield in the absence of target organism. The amount will vary depending on the pest to be controlled, the type of crop, the climatic conditions and the compounds included in the pesticidal composition. This amount can be determined by systematic field trials, which are within the capabilities of a person skilled in the art.

Depending on their particular physical and/or chemical properties, the active compounds of the invention can be formulated as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, microencapsulations in polymeric substances and in coating materials for seed, and also as ULV cold and warm fogging formulations.

The active compounds can be used neat, or in the form of a formulation, e.g. ready-to-use solutions, emulsions, water-or oil-based suspensions, powders, wettable powders, pastes, soluble powders, dusts, soluble granules, granules for broadcasting, suspoemulsion concentrates, natural substances impregnated with active compound, synthetic substances impregnated with active compound, fertilizers and also microencapsulations in polymeric substances. Application may be carried out, for example, by watering, spraying, atomising, broadcasting, dusting, foaming, spreading, etc. It is also possible to apply the active compounds by the ultra-low volume method or to inject the preparation of active compound or the active compound itself into the soil. It is also possible to treat the seed of the plants.

Formulations containing the compounds of the invention are produced in a known manner, for example by mixing the compounds with extenders (e.g. liquid solvents and/or solid carriers), optionally with the use of surfactants (e.g. emulsifiers and/or dispersants and/or foam-formers). The formulations are prepared either in factories/production plants or alternatively before or during the application.

Auxiliaries are substances which are suitable for imparting to the composition itself and/or to preparations derived therefrom (for example; spray liquors, seed dressings) particular properties such as certain technical properties and/or also particular biological properties. Typical suitable auxiliaries are: extenders, solvents and carriers.

Suitable extenders are, for example, water, polar and nonpolar organic chemical liquids, for example from the classes of the aromatic and non-aromatic hydrocarbons (such as paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes), the alcohols and polyols (which, if appropriate, may also be substituted, etherified and/or esterified), the ketones (such as acetone, cyclohexanone), esters (including fats and oils) and (poly)ethers, the unsubsfituted and substituted amines, amides, lactams (such as N-alkylpyrrolidones) and lactones, the sulfones and sulfoxides (such as dimethyl sulfoxide).

If the extender used is water, it is also possible to use, for example, organic solvents as auxiliary solvents. Essentially, suitable liquid solvents are: aromatics such as xylene, toluene or alkylnaphthalenes; chlorinated aromatics and chlorinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride; aliphatic hydrocarbons such as cyclohexane or paraffins, for example 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.

Suitable solid carriers are: for example, ammonium salts and ground natural minerals such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as finely divided silica, alumina and silicates; suitable solid carriers for granules are: for example, crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, and also synthetic granules of inorganic and organic meals, and granules of organic material such as paper, sawdust, coconut shells, maize cobs and tobacco stalks; suitable emulsifiers and/or foam-formers are: for example, nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers, alkylsulfonates, alkyl sulfates, arylsulfonates and also protein hydrolysates; suitable dispersants are nonionic and/or ionic substances, for example from the classes of the alcohol-POE and/or -POP ethers, acid and/or POP-POE esters, alkylaryl and/or POP-POE ethers, fat-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 arylsulfonates and alkyl or aryl phosphates or the corresponding PO-ether adducts. Furthermore, suitable oligo-or polymers, for example those derived from vinylic monomers, from acrylic acid, from EO and/or PO alone or in combination with, for example, (poly)alcohols or (poly)amines. It is also possible to employ lignin and its sulfonic acid derivatives, unmodified and modified celluloses, aromatic and/or aliphatic sulfonic acids and their adducts with formaldehyde.

Tackifiers such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or lattices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, as well as natural phospholipids such as cephalins and lecithins, and synthetic phospholipids, can be used in the formulations.

Further additives may be mineral and vegetable oils. It is also possible to add colourants such as inorganic pigments, for example iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs and metal phthalocyanine dyestuffs, and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc. Other possible additives are perfumes, mineral or vegetable, optionally modified oils and waxes.

The formulations may also comprise stabilizers, e.g. low-temperature stabilizers, preservatives, antioxidants, light stabilizers or other agents which improve chemical and/or physical stability.

The formulations generally comprise between 0.01 and 98% by weight of active compound, preferably between 0.1 and 95% and particularly preferably between 0.5 and 90%.

The active compounds of the invention can also be used as a mixture with other known fungicides, for example, to improve the activity spectrum or to reduce or slow the development of resistance. A mixture with other known active compounds such as nematicides, herbicides, insecticides, acaricides, or bactericides, or with fertilizers and growth regulators, safeners or semiochemicals is also possible.

Exemplary application rates of the active compounds according to the invention are: when treating leaves: from 0.1 to 10 000 g/ha, preferably from 10 to 1000 g/ha, particularly preferably from 50 to 300 g/ha (when the application is carried out by watering or dripping, it is even possible to reduce the application rate, especially when inert substrates such as rock wool or perlite are used); when treating seed: from 2 to 200 g per 100 kg of seed, preferably from 2.5 to 150 g per 100 kg of seed, and particularly preferably from 2.5 to 25 g per 100 kg of seed, very particularly preferably from 2.5 to 12.5 g per 100 kg of seed; when treating the soil: from 0.1 to 10000 g/ha, preferably from 1 to 5000 g/ha.

The compositions according to the invention are suitable for protecting any plant variety which is employed in agriculture, in the greenhouse, in forests or in horticulture and, in particular, cereals (e.g. wheat, barley, rye, millet and oats), maize, cotton, soya beans, rice, potatoes, sunflowers, beans, coffee, beet (for example sugar beet and fodder beet), peanuts, vegetables (e.g. tomatoes, cucumbers, onions and lettuce), lawns, fruit and nut trees (e.g. apples, pears, peaches, nectarines, apricots, hazelnut, pecan, macadamia, pistachio), soft fruit (e.g. strawberries, raspberries, blackcurrants, redcurrants), grapevines, bananas, cocoa and ornamental plants.

The active compounds of the invention, in combination with good plant tolerance and favourable toxicity to warm-blooded animals and being tolerated well by the environment, are suitable for protecting plants and plant organs, for increasing the harvest yields, for improving the quality of the harvested material and for controlling pests, in particular fungal diseases, which are encountered in agriculture, in horticulture, in animal husbandry, in forests, in gardens and leisure facilities, in the protection of stored products and of materials, and in the hygiene sector. They may be preferably employed as crop protection agents.

Use as fungicides The compounds of the invention have activity as fungicides.

The following are illustrative examples of agricultural pests that may be controlled by fungicidal compounds: Powdery mildew diseases such as: Blumeria diseases, caused for example by Blumeria graminis; Podosphaera diseases, caused for example by Podosphaera leucotheca; Sphaerotheca diseases, caused for example by Sphaerotheca fuliginea; Uncinula diseases, caused for example by Uncinula necator; Rust diseases such as: Gymnosporangium diseases, caused for example by Gymnosporangium sabinae. Hemileia diseases, caused for example by Hemileia vastafix; Phakopsora diseases, caused for example by Phakopsora pachyrhizi or Phakopsora meibomiae; Puccinia diseases, caused for example by Puccinia recondita; Uromyces diseases, caused for example by Uromyces appendiculatus; Oomycete diseases such as: Albugo diseases caused for example by Albugo Candida; Bremia diseases, caused for example by Bremia lactucae; Peronospora diseases, caused for example by Peronospora pisi or P. brassicae; Phytophthora diseases, caused for example by Phytophthora infestans; Plasmopara diseases, caused for example by Plasmopara vificola; Pseudoperonospora diseases, caused for example by Pseudoperonospora humuli or Pseudoperonospora cubensis; Pythium diseases, caused for example by Pythium ultimum; Leafspot, leaf blotch and leaf blight diseases such as: Alternaria diseases, caused for example by Alternaria solani; Cercospora diseases, caused for example by Cercospora beticola; Cladiosporum diseases, caused for example by Cladiosporium cucumerinum; Cochliobolus diseases, caused for example by Cochliobolus sativus; Colletotrichum diseases, caused for example by Colletotrichum lindemuthanium; Cycloconium diseases, caused for example by Cycloconium oleaginum; Diaporthe diseases, caused for example by Diaporthe citri; Drechslera, Syn: Helminthosporium) or Cochliobolus miyabeanus; Elsinoe diseases, caused for example by Elsinoe fawcettii; Gloeosporium diseases, caused for example by Gloeosporium laeticolor; Glomerella diseases, caused for example by Glomerella cingulata; Guignardia diseases, caused for example by Guignardia bidwelli; Leptosphaeria diseases, caused for example by Leptosphaeria maculans; Leptosphaeria nodorum; Magnaporthe diseases, caused for example by Magnaporthe grisea; Mycosphaerella diseases, caused for example by Mycosphaerella graminicola; Mycosphaerella arachidtola; Mycosphaerella fibensis; Phaeosphaeria diseases, caused for example by Phaeosphaera nodorum; Pyrenophora diseases, caused for example by Pyrenophora teres; Ramularia diseases, caused for example by Ramularia collo-cygni; Rhynchosporium diseases, caused for example by Rhynchosporium secalis; Septoria diseases, caused for example by Septoria apii or Septoria lycopercisi; Typhula diseases, caused for example by Typhula incarnate; Venturia diseases, caused for example by Venturia inaequalis; Root and stem diseases such as: Corticium diseases, caused for example by Corticium graminearum; Fusarium diseases, caused for example by Fusarium oxysporum; Gaeumannomyces diseases, caused for example by Gaeumannomyces graminis; Rhizoctonia diseases, caused for example by Rhizoctonia solani; Sarocladium diseases caused for example by Sarocladium oryzae; Sclerotium diseases caused for example by Sclerotium oryzae; Tapesia diseases, caused for example by Tapesia acuformis; Thielavbpsis diseases, caused for example by Thielaviopsis basicola; Ear and panicle diseases including maize cob, such as: Alternaria diseases, caused for example by Alternaria spp.; Aspergillus diseases, caused for example by Aspergillus flavus; Cladosporium diseases, caused for example by Cladosporium spp.; Claviceps diseases, caused for example by Claviceps purpurea; Fusarium diseases, caused for example by Fusarium culmorum; Gibberella diseases, caused for example by Gibberella zeae; Monographella diseases, caused for example by Monographella nivalis; Smut and bunt diseases such as: Sphacelotheca diseases, caused for example by Sphacelotheca reiliana; Tilletia diseases, caused for example by Tilletia caries; Urocystis diseases, caused for example by Urocystis occulta; Ustilago diseases, caused for example by Usfilago nuda; Fruit rot and mould diseases such as: Aspergillus diseases, caused for example by Aspergillus flavus; Botrytis diseases, caused for example by Botrytis cinerea; Penicillium diseases, caused for example by Penicillium expansum; Rhizopus diseases caused for example by Rhizopus stolonifer; Sclerofinia diseases, caused for example by Sclerotinia sclerotiorum; Verticilium diseases, caused for example by Verticilium alboatrum; Seed and soil borne decay, mould, wilt, rot and damping-off diseases such as: Alternaria diseases, caused for example by Alternaria brassicicola; Aphanomyces diseases, caused for example by Aphanomyces euteiches; Ascochyta diseases, caused for example by Ascochyta lentis; Aspergillus diseases, caused for example by Aspergillus flavus; Cladosporium diseases, caused for example by Cladosporium herbarum; Cochliobolus diseases, caused for example by Cochliobolus safivus (Conidiaform: Drechslera, Bipolaris Syn: Helminthosporium); Colletotrichum diseases, caused for example by Colletotrichum coccodes; Fusarium diseases, caused for example by Fusarium culmorum; Gibberella diseases, caused for example by Gibberella zeae; Macrophomina diseases, caused for example by Macrophomina phaseolina; Monographella diseases, caused for example by Monographella nivalis; Penicillium diseases, caused for example by Penicillium expansum; Phoma diseases, caused for example by Phoma lingam; Phomopsis diseases, caused for example by Phomopsis sojae; Phytophthora diseases, caused for example by Phytophthora cactorum; Pyrenophora diseases, caused for example by Pyrenophora graminea; Pyricularia diseases, caused for example by Pyricularia oryzae; Pythium diseases, caused for example by Pythium ultimum; Rhizoctonia diseases, caused for example by Rhizoctonia solani; Rhizopus diseases, caused for example by Rhizopus oryzae; Sclerotium diseases, caused for example by Sclerotium rolfsii; Septoria diseases, caused for example by Septoria nodorum; Typhula diseases, caused for example by Typhula incarnata; Verticillium diseases, caused for example by Verticillium dahliae; Canker, broom and dieback diseases such as: Nectria diseases, caused for example by Nectria galligena; Blight diseases such as: Monilinia diseases, caused for example by Monilinia laxa; Leaf blister or leaf curl diseases such as: Exobasidium diseases caused for example by Exobasidium vexans; Taphrina diseases, caused for example by Taphrina deformans; Decline diseases of wooden plants such as: Esca diseases, caused for example by Phaemoniella clamydospora, Phaeomoniella clamydospora, Phaeoacremonium aleophilum and Fomitiporia mediterranea; Eutypa dyeback, caused for example by Eutypa lata; Dutch elm disease, caused for example by Ceratocystsc ulmi; Ganoderma diseases caused for example by Ganoderma boninense; Diseases of flowers and seeds such as: Botrytis diseases, caused for example by Botrytis cinerea; Diseases of tubers such as: Rhizoctonia diseases, caused for example by Rhizoctonia solani Helminthosporium diseases, caused for example by Helminthospohum solani.

Diseases of Tubers such as: Rhizoctonia diseases caused for example by Rhizoctonia solani Helminthosporium diseases caused for example by Helminthospohum solani; Club root diseases such as: Plasmodiophora diseases, caused for example by Plamodiophora brassicae.

The compounds of the invention may be active against a broad spectrum of fungal diseases of plants. Alternatively, they may be active specifically against certain specific fungal diseases.

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

In additional to their fungicidal activity, the compounds of the invention may also have activity against other microbes, e.g. bacteria.

The fungicidal compounds of the invention may also be used in the treatment of fungal diseases of humans and animals (e.g. mammals). Likewise, the bactericidal compounds of the invention may be used in the treatment of bacterial diseases of humans and animals.

Thus, the invention includes a method of treating a fungal or bacterial disease, the method comprising of administering a therapeutic amount of an antifungal agent of the invention to a subject (e.g. a human subject) in need thereof The compound may be formulated for topical administration to the infected area of the body or it may be formulated for oral or parenteral administration.

Synthesis The skilled person will appreciate that adaptation of methods known in the art could be applied in the manufacture of the compounds of the present invention.

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

The skilled person is familiar with a range of strategies for synthesising organic and particularly heterocyclic molecules and these represent common general knowledge as set out in text books such as Warren "Organic Synthesis: The Disconnection Approach"; Mackie and Smith "Guidebook to Organic Chemistry"; and Clayden, Greeves, Warren and Wothers "Organic Chemistry".

The skilled person will exercise his/her judgement and skill as to the most efficient sequence of reactions for the synthesis of a given target compound and will employ 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 influence the choice of reagent that is used in the said synthetic steps, the need, and type, of protecting groups that are employed, and the sequence for accomplishing the protection/deprotection steps. These and other reaction parameters will be evident to the skilled person by reference to standard textbooks and to the examples provided herein.

Sensitive functional groups may need to be protected and deprotected during synthesis of a compound of the invention. This may be achieved by conventional methods, for example as described in "Protective Groups in Organic Synthesis" by TW Greene and PGM Wuts, John Wiley & Sons Inc. (1999), and references therein.

Throughout this specification these abbreviations have the following meanings: Throughout this specification these abbreviations have the following meanings: PyBOP -benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate HATU - (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate DI PEA -N,N-diisopropylethylamine DMSO -dimethylsulfoxide aq. -aqueous conc. -concentrated DCM -dichloromethane DMF -N,N-dimethylformamide h -hour mm-minute LCMS -liquid chromatography mass spectrometry r.t. -room temperature PE -petroleum ether THF -tetrahydrofuran Et0Ac -ethyl acetate Me0H -methanol Certain compounds of the invention can be accessed according to or analogously to the general synthetic schemes below. Certain compounds of the invention can be accessed via the synthetic intermediates described in Examples 1 to 15 below.

General Synthetic Schemes Compounds of formula I can be made according to scheme A or scheme B. Benzothiazoles of formula A are commercially available. Activating group X on benzothiazole A can be used as a handle to introduce R6 and provide benzothiazole B. R6 can be introduced using coupling reactions (e.g. Buchwald-Hartwig, Suzuki) with a suitable coupling partner in which case X may be a halogen, e.g. bromide, or a boronic ester. Alternatively, R6 can be introduced using an addition elimination reaction, in which case X may be a leaving groups, such as a halogen, e.g chloro, or a sulfonate, e.g. methylsulfonate. Addition/elimination reactions are particularly appropriate where R6 is Z2R6a and Z2 is 0, S or NR7. In these reactions, benzothiazole A is typically treated with R63-Z2-H in the presence of a base (e.g. NaH or Na2CO3). Reduction of the nitro group, e.g. using Fe and NH4CI, or Pd/C and H2, then provides amine C. Where R4 is not H, R4 can be introduced at this stage, e.g. using an alkyl halide. Amide formation with picolinic acid derivative D (e.g. using HATU) forms compounds of formula E, a subset of compounds of the invention.

(R5)," (R5)," 02N Scheme A Compounds of formula E can be converted to compounds of formula F (e.g. using Ac20) or G (e.g. using either thiophosgene where Y2 is S or triphosgene where Y2 is 0), two further subsets of compounds of the invention.

Scheme B

EXAMPLES

General Methods Flash chromatography was carried out using a Biotage Isolera 4, with Biotage® SNAP KP-Sil cartridges, packed with 50 pm silica particles with a surface area of 500 m2/g, or alternative cartridges (e.g. Puriflash, produced by Interchim) where stated, or using silica gel (40-63 pm particles). Visualisation was carried out with UV light (254 nm) and by staining with either potassium permanganate, phosphomolybdic acid (PMA) or ninhydrin solutions.

All 1H NMR spectra were obtained on a Bruker AVIII 400 with 5mm QNP or Bruker AVI 500 with 5mm QNP. Chemical shifts are expressed in parts per million (5) and are referenced to the solvent. Coupling constants J are expressed in Hertz (Hz).

LCMS was carried out on a Waters Alliance ZQ MS, using a YMC-Triart C18 50 x 2 mm, 5 micron LC column (solvent: 5-90% gradient of acetonitrile in water (with 1% by volume of 28% (by weight) aqueous ammonia solution)) by Method A, or (solvent: 5-90% gradient of acetonitrile in water (with 1% formic acid)) by Method B. Flow rate: 0.8 mUmin. Wavelengths were 254 and 210 nm.

Method A (5 minute basic pH) Column: YMC-Triart C18 50 x 2 mm, 5 pm. Flow rate: 0.8 mUmin. Injection volume: 5 pL. OAc H(N

)n-N 0 (R5), R20 Mobile Phase A H20 CH3CN 50% H20 / 50% CH3CN + 1.0% ammonia (aq.) Time A (%) B (%) C (%) (min) 0 95 0 5 4.0 0 95 5 4.4 0 95 5 4.5 95 5 0 4.5 STOP Method B (5 minute acidic pH) Column: YMC-Triart C18 50 x 2 mm, 5 pm. Flow rate: 0.8 mdmin. Injection volume: 5 pL.

Mobile Phase A H20 CH3CN 50% H20 /50% CH3CN + 1.0% formic acid Time A (%) B (%) C (%) (min) 0 95 0 5 4.0 0 95 5 4.4 0 95 5 4.5 95 5 0 4.5 STOP All reagents were obtained from commercial suppliers and used as supplied unless otherwise stated.

All compounds are named using ChemBioDraw Ultra 14.0.

Intermediate A: 2-(4-fluorophenoxy)-6-nitrobenzo[d]thiazole 02N 4-Fluorophenol (131 mg, 1.17 mmol) was dissolved in DMF (2 mL), and sodium hydride (60% in mineral oil) (65.2 mg, 1.63 mmol) was added. After stirring for 5 min, 2-chloro-6-nitro-benzothiazole (250 mg, 1.17 mmol) was added. The reaction was stirred at r.t. for 18 h, then quenched by pouring into cold water 20 mL). After stirring for 15 min, the suspension was filtered. The solid was washed with water and dried under vacuum to obtain the title compound as a beige solid (286 mg, 85%). 1H NMR OH (400 MHz, CDCI3) 08.66 (d, J = 2.3 Hz, 1H), 8.32 (dd, J= 8.9, 2.3 Hz, 1H), 7.82 (d, J= 8.9 Hz, 1H), 7.42 -7.36 (m, 2H), 7.24 -7.17 (m, 2H). LCMS (Method A): 3.50 min, (no mass detected).

Intermediates B -D: The following Intermediates were prepared using the general method described in intermediate A from commercial materials.

Intermediate Compound 1FI NMR/LCMS No B 2-(4-fluorophenoxy)-5-nitrobenzoldjthiazole 1H NMR Oh (400 MHz, CDCI3) 8.60 (d, J = 2.2 Hz, 1H), 8.21 (dd, J= 8.8, 2.2 Hz, 1H), 7.85 (d, J= 8.8 Hz, 1H), 7.43 -7.35 (m, 2H), 7.24 -7.15 (m, 2H); LCMS (Method A): 3.48 min (291.0, MH*).

F 02N a \ S0

S

C N-(4-fluoropheny1)-N-methyl-6-nitrobenzordithiazol-2-amine 1H NMR OH (400 MHz, CDCI3) 8.44 (d, J = 2.3 Hz, 1H), 8.24 (dd, J= 8.9, 2.3 Hz, 1H), 7.62 (d, J= 8.9 Hz, 1H), 7.46 -7.38 (m, 2H), 7.27 -7.20 (m, 2H), 3.68 (s, 3H); LCMS (Method A): 3.48 min (304.0, MW).

F 02N ao s / N \

D N-(4-fluoropheny1)-N-methyl-5-nitrobenzold]thiazol-2-amine 1H NMR Oh (400 MHz, CDCI3) 8.45 (d, J= 2.1 Hz, 1H), 7.98 (dd, J= 8.6, 2.2 Hz, 1H), 7.61 (d, J= 8.6 Hz, 1H), 7.47 -7.38 (m, 2H), 7.26 -7.17 (m, 2H), 3.66 (s, 3H); LCMS (Method A): 3.56 min (304.0, MW).

F 02N. \ 0 S \

N

Intermediate E: 2((4-fluorophenyOthio)-6-nitrobenzoldithiazole 02N 4-Fluorobenzenethiol (0.124 mL, 1.17 mmol) was dissolved in DMF (2 mL), and potassium carbonate (161 mg, 1.17 mmol) was added. After stirring fors min, 2-chloro-6-nitro-benzothiazole (250 mg, 1.17 mmol) was added. The reaction was stirred at 60°C for 18 h, then quenched by pouring into cold water 20 mL). After stirring for 15 min, the suspension was filtered. The solid was washed with water and dried under vacuum to obtain the title compound as a tan solid (326 mg, 91 %). 1H NMR Oh (400 MHz, CDCI3) 6 8.61 (d, J = 2.3 Hz, 1H), 8.32 (dd, J = 9.0, 2.3 Hz, 1H), 7.94 (d, J = 9.0 Hz, 1H), 7.83 -7.76 (m, 2H), 7.31 -7.23 (m, 2H). LCMS (Method A): 3.74 min, (306.9, MH+).

Intermediate F: The following Intermediate was prepared using the general method described in Intermediate E from commercial materials.

Intermediate Compound 1H NMR/LCMS No F 2((4-fluorophenyOthio)-5-nitrobenzoldjthiazole 1H NMR Oh (400 MHz, CDCI3) 8.71 (d, J = 2.2 Hz, 1H), 8.18 (dd, J= 8.8, 2.2 Hz, 1H), 7.83 -7.74 (m, 3H), 7.31 -7.21 (m, 2H); LCMS (Method A): 3.50 min (306.9, MW).

F 02N a

siii \ S

S

Intermediate G: 2-(4-fluorophemaxy)benzotdithiazol-6-amine

H N

Intermediate A (286 mg, 0.99 mmol) was dissolved in THF (5 mL)/Me0H (2.5 mL)/water (1.5 mL), and iron (275 mg, 4.93 mmol) and ammonium chloride (264 mg, 4.93 mmol) were added. The reaction was stirred at 60 °C for 4 h. After cooling to r.t., the mixture was filtered through Dicalite®, washing with Et0Ac. The filtrate was washed with water, and the aqueous layer extracted with Et0Ac. The combined organics were washed (brine), dried (Mg304) and concentrated in vacuo to yield the title compound as a yellow solid (245 mg, 96 °/0). 1H NMR Oh (400 MHz, CDCI3) 6 7.53 (d, J = 8.6 Hz, 1H), 7.37 -7.31 (m, 2H), 7.17 -7.09 (m, 2H), 6.98 (d, J = 2.3 Hz, 1H), 6.77 (dd, J = 8.6, 2.4 Hz, 1H), 3.74 (br s, 2H). LCMS (Method A): 2.83 min, (261.1, MH*).

Intermediates H -L: The following Intermediates were prepared using the general method described in intermediate G from the appropriate intermediate.

Intermediate Compound 1H NMR/LCMS No H 2-(4- 1H NMR Oh (400 MHz, CDCI3) 7.43 (d, J = 8.5 Hz, 1H), 7.37 -7.31 (m, 2H), 7.18 -7.11 (m, 2H), 7.08 (d, J= 2.3 Hz, 1H), 6.70 (dd, J= 8.5, 2.3 Hz, 1H), 3.77 (br s, 2H); LCMS (Method A): 2.86 min (261.0, MH*).

fluorophenoxy)benzord]thiazol-5-amine

F H2N.

0 s,-° I N2-(4-fluoropheny1)-N2-methylbenzoldlthiazole-2,6-diamine 1H NMR OH (400 MHz, CDCI3) 7.44 (d, J = 8.5 Hz, 1H), 7.42 -7.37 (m, 2H), 7.20 -7.10 (m, 2H), 6.87 (d, J= 2.3 Hz, 1H), 6.71 (dd, J= 8.5, 2.4 Hz, 1H), 3.58 (s, 5H); LCMS (Method A): 2.75 min (274.0, MW).

F

H2N 41 0 s / N \ J 2-((4- 1H NMR Oh (400 MHz, CDCI3) 7.75 -7.66 (m, 3H), 7.20 -7.12 (m, 2H), 6.95 (d, J = 2.3 Hz, 1H), 6.79 (dd, J= 8.6, 2.2 Hz, 1H), 3.79 (br s, 2H); LCMS (Method A): 3.15 min (277.0, MH*).

fluorophenyOthio)benzo[d]thiazol-6-amine

F

H2N 4I 0 S i S K N2-(4-fluoropheny1)-N2-methylbenzoldithiazole-2,5-diamine 1H NMR Oh (400 MHz, CDCI3) 7.44 -7.37 (m, 2H), 7.27 (d, J = 8.3 Hz, 1H), 7.20 -7.12 (m, 2H), 6.99 (d, J= 2.2 Hz, 1H), 6.52 (dd, J= 8.3, 2.2 Hz, 1H), 3.70 (br s, 2H), 3.60 (s, 3H); LCMS (Method A): 2.81 min (274.0, MH*).

F H2N. \

N S \

L 244- 1H NMR OH (400 MHz, CDCI3) 7.77 -7.70 (m, 2H), 7.42 (d, J = 8.5 Hz, 1H), 7.22 -7.15 (m, 3H), 6.71 (dd, J = 8.5, 2.2 Hz, 1H), 3.81 (br s, 2H); LCMS (Method A): 3.08 min (277.0, MW).

fluorophenyOthio)benzo[d]thiazol-5-amine H2N Example 1: N-(2-(4-fluorophenoxy)benzolcuthiazol-6-y0-3-hydroxy-4-methoxypicolinamide Me0 OH -N 0 DIPEA (0.268 mL, 1.54 mmol) and HATU (219 mg, 0.58 mmol) were added to a solution of Intermediate G (100 mg, 0.384 mmol) and 3-hydroxy-4-methoxy-2-pyridinecarbmdic acid (78 mg, 0.46 mmol) in acetonitrile (2 mL). The mixture was stirred at r.t. for 18 h. Water (-3 mL) was added and the resultant suspension was filtered. The solid was washed (water/Et0Ac) and dried under vacuum to obtain the title compound as a pink solid (21 mg, 14%). 1H NMR oh (400 MHz, DMSO-d6) 012.23 (br s, 1H), 11.01 (br s, 1H), 8.53 -8.40 (m, 1H), 8.23 -8.10 (m, 1H), 7.87 -7.73 (m, 1H), 7.70 (d, J= 8.7 Hz, 1H), 7.63 -7.48 (m, 2H), 7.42 -7.32 (m, 2H), 7.32 -7.20 (m, 1H), 3.93 (s, 3H). LCMS (Method A): 3.04 min, (412.0, MH*).

Example 2: N-(2-(4-fluorophenoxy) benzoftlfthiazol-5-y0-3-hydroxy-4-methoxypicolinamide

N

HN

DIPEA (0.134 mL, 0.77 mmol) and PyBOP (100 mg, 0.19 mmol) were added to a solution of Intermediate H (50 mg, 0.19 mmol) and 3-hydroxy-4-methoxy-2-pyridinecarboxylic acid (39 mg, 0.23 mmol) in DCM (2 mL). The mixture was stirred at r.t. for 18 h. The mixture was reduced in volume in vacuo, then water (-2 mL) was added and the resultant suspension was filtered. The solid was washed (water/Et0Ac) and dried under vacuum to obtain the title compound as a grey solid (36 mg, 45%). 1H NMR OH (400 MHz, DMSO-de) 6 12.21 (s, 1H), 11.01 (s, 1H), 8.22 (br s, 1H), 8.16 (d, J = 5.2 Hz, 1H), 7.93 (d, J= 8.6 Hz, 1H), 7.84 (d, J= 9.9 Hz, 1H), 7.60 -7.52 (m, 2H), 7.46 -7.34 (m, 2H), 7.28 (d, J = 5.1 Hz, 1H), 3.93 (s, 3H). LCMS (Method A): 2.34 min, (412.0, MH*).

Examples 3 -6:

The following Examples were prepared using the general method described in Example 2 from the appropriate intermediate.

Example No Compound IHNMRJLCMS 3 N-(2-((4- 11-I NMR OH (400 MHz, DMSO-d6) 12.32 (s, 1H), 10.86 (s, 1H), 8.21 (d, J = 1.9 Hz, 1H), 8.14 (d, J = 5.2 Hz, 1H), 7.71 (dd, J = 8.8, 1.9 Hz, 1H), 7.65 -7.58 (m, 2H), 7.55 -7.49 m 1H fluoropheny0(methy0amino)benzoldithiaz ol-6-y0-3-hydroxy-4-methoxypicolinamide ( , 1H),7.41 -7.33 I) _N (m, 2H), 7.26 (d, J = 5.2 Hz, 1H), 3.92 (s, 3H), 3.54 (s, 3H); LCMS (Method A): 2.66 min (425.1, MH*). ___"

M 0 OH (II 0 / .

HN F -N 0

4 N-(2((4-fluorophenyOthio) benzoMthiazol-6-y0-3-hydroxy-4-methoxypicolinamide 1H NMR OH (400 MHz, DMSO-cr) 12.16 (br s, 1H), 11.03 (br s, 1H), 8.44 (s, 1H), 8.22 -8.07 (m, 1H), 7.96 -7.81 (m, 4H), 7.51 -7.39 (m, 2H), 7.31 -7.20 (m, 1H), 3.92 (s, 3H); LCMS (Method A): 2.82 min (428.0, MH*).

S--..",--S N 0 Me0 OH II

HN F

-N

N-(2-((4- 1H NMR OH (400 MHz, DMSO-d6) 12.30 (s, 1H), 10.87 (s, 1H), 8.18 -8.14 (m, 1H), 8.08 -8.04 (m, 1H), 7.70 -7.54 (m, 4H), 7.41 -7.33 (m, 2H), 7.30 -7.25 (m, 1H), 3.93(s, 3H), 3.55 (s, 3H); LCMS (Method A): 2.58 min (425.1, MH*).

fluoropheny0(methy0amino)benzo[dIthiaz ol-5-y0-3-hydroxy-4-methoxypicolinamide

I

NN

Me0 OH k. ,c Hp F

-N

6 N-(2((4-fluorophenyOthio) benzordlthiazol-5-y0-3-hydroxy-4-methoxypicolinamide 1H NMR E,Ei (400 MHz, DMSO-d6) 12.18 (br s, 1H), 11.04 (br s, 1H), 8.41 (s, 1H), 8.16 (br m, 1H), 7.98 -7.87 (m, 3H), 7.82 (br m, 1H), 7.51 -7.38 (m, 2H), 7.27 (br m, 1H), 3.93 (s, 3H); LCMS (Method A): 2.83 min (428.0, MW). Nc.,S le

Me0 OH it

HN F 4',

-N

Example 7: 24(2-(4-fluorophenoxy)benzo[d]thiazol-6-y0carbamoy0-4-methoxypyridin-3-yl acetate MoO OAc

HN -N 0

Acetic anhydride (0.064 mL, 0.681 mmol) was added to a solution of Example 1(14 mg, 0.034 mmol) in pyridine (0.5 mL) and stirred at r.t. for 1h. The reaction was concentrated in vacuo. The residue was purified by column chromatography (Si02, 0-100% Et0Ac in PE) and the title compound was isolated as an orange solid (10 mg, 68%). 1H NMR Oh (500 MHz, DM30-a6) 10.72 (s, 1H), 8.51 (d, J= 5.5 Hz, 1H), 8.49 (d, J= 2.0 Hz, 1H), 7.75 (dd, J= 8.8, 2.1 Hz, 1H), 7.66 (d, J= 8.8 Hz, 1H), 7.58 -7.50 (m, 2H), 7.46 (d, J = 5.6 Hz, 1H), 7.41 -7.33 (m, 2H), 3.94 (s, 3H), 2.30 (s, 3H); LCMS (Method B): 3.16 min, (454.0, MH*).

Examples 8 -12:

The following Examples were prepared using the general method described in Example 7 from the appropriate intermediate.

Example No Compound 1FI NMR/LCMS 8 242-(4-fluorophenoxy)benzo[clIthiazol-5-yucarbamoy1)-4-methoxypyridth-3-yl acetate 1H NMR Oh (400 MHz, DMSO-a6) 10.71 (s, 1H), 8.51 (d, J = 5.5 Hz, 1H), 8.24 (d, J = 2.0 Hz, 1H), 7.89 (d, J= 8.7 Hz, 1H), 7.75 (dd, J = 8.8, 2.0 Hz, 1H), 7.58 -7.52 (m, 2H), 7.46 (d, J = 5.6 Hz, 1H), 7.41 -7.34 (m, 2H), 3.94 (s, 3H), 2.30 (s, 3H); LCMS (Method B): 3.17 min (454.0, MI-1). N 0 t

Me0 OAc 4. S 0

iHN ',, F

-N

9 2-((2-((4- 1H NMR Oh (400 MHz, DMSO-a6) 10.55 (s, 1H), 8.49 (d, J = 5.5 Hz, 1H), 8.19 (d, J = 2.0 Hz, 1H), 7.67 -7.58 (m, 3H), 7.49 (d, J= 8.7 Hz, 1H), 7.44 (d, J = 5.6 Hz, 1H), 7.40 -7.33 (m, 2H), 3.97 -3.90 (m, 3H), 3.53 (s, 3H), 2.29 (s, 3H); LCMS (Method B): 3.09 min (467.2, MH+).

fluorophenyl)(methygamino)benzoblitM azol-6-yOcarbamoy1)-4-methoxypyridth-3-y1 acetate

I N

Me0 OAc /

N

HN F i. $ ,

-N

2-((2-((4- 1H NMR Oh (400 MHz, DMSO-a6) fluorophenyOthio)benzorclithiazol-6-yl)carbamoy0-4-methoxypyridin-3-y1 10.75 (s, 1H), 8.50 (d, J = 5.5 Hz, 1H), 8.46 (s, 1H), 7.93 -7.85 (m, acetate 2H), 7.82 (s, 2H), 7.51 -7.39 (m, 3H), 3.94 (s, 3H), 2.29 (s, 3H): LCMS (Method B): 3.44 min

S S

Me0 OAc I N / .

HN F i

(470.1, MH *).

-N

11 2-((2-((4- 1H NMR Oh (400 MHz, DMSO-cr) fluoropheny0(methyDamino)benzcidithi azol-5-yOcarbamoy0-4-methoxypyridin- 10.57 (s, 1H), 8.51 (d, J = 5.5 Hz, 1H), 8.07 (d, J= 1.9 Hz, 1H), 7.65 3-y1 acetate -7.57 (m, 3H), 7.51 (dd, J= 8.6, 1.9 Hz, 1H), 7.46 (d, J = 5.6 Hz,

I

N

1H), 7.41 -7.32 (m, 2H), 3.95 (s, 3H), 3.54 (s, 3H), 2.31 (s, 3H); Me0 OAc s 1110 *

HN F

1. LCMS (Method B): 3.14 min

-N

(467.1, MH*).

12 2-((2-((4- 1H NMR Oh (400 MHz, DMSO-cla) fluorophenyOthio)benzorcljthiazol-5-yl)carbamoy1)-4-methoxypyridin-3-y1 10.76 (s, 1H), 8.51 (d, J = 5.5 Hz, 1H), 8.45-8.38 (m, 1H), 7.96 -acetate 7.84 (m, 4H), 7.76 (dd, J= 8.8, 2.0 ----7-- Hz, 1H), 7.51 -7.41 (m, 2H), 3.95 Me0 OAG S 0 * (s, 3H), 2.31 (s, 3H); LCMS (Method B): 3.43 min (470.1, MH+). Fp J\ F

-N

Example 13: 3-(24(4-fluorophenyl)(methyl)amino)benzofdlthiazol-6-0) -8-methoxy-2-thioxo-2,3-dihydro-4H-pyrido[2,3-eff1,31oxazin-4-one OMe 0 S Thiophosgene (0.023 mL, 0.303 mmol) was added to a solution of Example 3(64 mg, 0.15 mmol) in DCM (1 mL). Pyridine (0.244 mL, 3.03 mmol) was added, and the reaction was stirred at r.t. for 1 h. The reaction mixture was purified by column chromatography (Si02, 0-100% Et0Ac in PE) and the title compound was isolated as a brown solid (28 mg, 40%). LCMS (Method B): 2.88 min (467.1, MH*).

Examples 14-15:

The following Examples were prepared using the general method described in Example 13 from the appropriate example.

Intermediate Compound 1FI NMR/LCMS No 14 3-(2-((4- LCMS (Method B): 3.15 min (470.0, MI-1+).

fluorophenyOthio)benzo[d]thiazol-6-y0-8-methoxy-2-thioxo-2, 3-dihydro-4H-pyridof2,3-e][1,31oxazin-4-one OMe -N&híL_}.."..0 S I t -iN 0 s 0*, s

F

3-(2-((4- LCMS (Method B): 2.94 min (467.0, MH+).

fluoropheny0(methyDamino)benzo [dithiazol-5-y0-8-methoxy-2-thioxo-2,3-dihydro-4H-pyrido[2,3-e][1, 31oxazin-4-one OMe N-11\1 0 * NI/

S 4.

F

Example 16: Testing the fungicidal activity of the compounds of the invention Compounds were screened in 96 well plates with 10 compounds per plate. Each compound was screened using agar amended to 20, 2, 0.2 and 0.02 ppm of the test material. Proline at 50 and 10 ppm and 0.2% DM50 were used respectively as positive and negative controls. Each test concentration and standard were tested twice on a plate.

Compounds were screened against Zymoseptoria tritici. The agar used in the test was 1% potato dextrose agar. Sufficient spores were added to the appropriate agar to give 10,000 spores/mL agar.

A x10 stock solution in 2% DMSO was produced for each dose i.e. 200, 20, 2 and 0.2 ppm, and 10 pl of this added to the appropriate wells on the plate. An equivalent amount of 2% DMSO and Proline stock at 500 and 100 ppm were added for the controls. To each well, 90 pl of the appropriate agar spore suspension was added to give the final well concentrations outlined in the first paragraph.

Plates were incubated at room temperature (18 °C) and assessed after 7 days.

The amount of fungal growth in each well was compared to the DMSO controls and scored according to the following key: A -EC50 <2 ppm B -2EC50<20 C -EC50 20 D -No activity detected at the highest dose tested NT -Not tested The ranking in the table is:

Example Zymoseptoria 1 A 2 B 3 A 4 A

A 6 C 7 A 8 A 9 B

A 11 A 12 A 13 B 14 A

A

Claims (19)

1. Claims 1. A compound of formula I, or an agronomically acceptable salt or N-oxide thereof: R61 wherein a single one of X' and X2 is S and a single one of X1 and X2 is N; Y1 is independently selected from 0 and S; R1, R5 and R15 are each independently at each occurrence selected from C1-Cs-alkyl, C1-C6-haloalkyl, Ca-C6-cycloalkyl, halogen, nitro, OR11, SR12, OS(0)2R12, S(0)2R12, C(0)0R12, C(0)NR12R12, C(0)R12, S(0)2NR12R12, S(0)(NR12)R12, S(0)R12, cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR12R13; R2 and Re are each independently selected from: H, C1-a4-alkyl, C3-C6-cycloalkyl, C(0)R14, C(0)0R14, CH20C(0)R14 and CH200(0)0R14; R4 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, C1-C6-alkyl and benzyl; or Re and R4 together form a group independently selected from C1-C2-alkylene, -C(0)-and -C(S)-; R6 is selected from R5 and -Z1-Z2-R"; wherein Rea is selected from C3-C8-alkyl and Co-C3-alkylene-Rea; wherein Rea is independently at each occurrence selected from phenyl, 5-or 6-membered heteroaryl, 5-, 6-, 7-or 8-membered heterocycloalkyl and C6-C8-cycloalkyl; said heterocycloalkyl or cycloalkyl group being monocyclic or bicyclic; said heteroaryl or phenyl group being optionally substituted with from 1 to 5 R15 groups or said heterocycloalkyl or cycloalkyl group being optionally substituted with from 1 to 4 R16 groups; Z1 is independently absent or is CIReRe; Z2 is independently at each occurrence absent or is selected from C(0)0, OC(0), 0, S, S(0), 25 S(0)2, C(0)NR7, NR7C(0), S(0)2NR7, NR7S(0)2, S(0)NR7, NR7S(0), CReRe, CReRe0, CReReNR7, C(0), C(S), C=NORle and NR7; R18 is independently at each occurrence selected from: =0, =S, C1C6-haloalkyl, C3-C6-cycloalkyl; halogen, nitro, OR11, SR12, OS(0)2R12, S(0)2R12, S(0)2NR12R12, S(0)(NR12)R12, S(0)R12, cyano, C2-C6-alkenyl, C2-C6-alkynyl, and NR12R'; R7 and R12 are each independently at each occurrence selected from: H, Ca-C6-cycloalkyl, Ci-Cs-alkyl and benzyl; or where two R12 groups are attached to the same nitrogen atom, said R12 groups, together with said nitrogen atom form a 4-, 5-, 6-or 7-membered heterocycloalkyl ring; R8 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, Ci-C6-alkyl, phenyl and 5-or 6-membered heteroaryl; R9 is independently at each occurrence selected from: H, halo and OR13; or R8 and R9 together with the carbon atom to which they are attached may form a C3-C6cycloalkyl ring or a 3-, 4-, 5-or 6-membered heterocycloalkyl ring; R13 is each independently at each occurrence selected from: H, C3-C6-cycloalkyl, and Ci-C3-alkylene-R139; wherein R139 is independently at each occurrence selected from phenyl and 5-or 6-membered heteroaryl; R11 is independently at each occurrence selected from: H, C3-C6-cycloalkyl, C(0)-Ci-C6-alkyl and Ci-C6-haloalkyl; R13 is independently at each occurrence selected from; H, C(0)-Ci-C6-alkyl and S(0)2-Ci-C6-alkyl; or where an R12 group and an R13 group are attached to the same nitrogen atom, said R12 and R13 groups, together with said nitrogen atom form a 4-, 5-, 6-or 7-membered heterocycloalkyl ring; R14 is independently at each occurrence selected from: Ci-C6-alkyl, phenyl, benzyl and 03-C6-cycloalkyl n is independently an integer selected from 0, 1 and 2; m is independently an integer selected from 0, 1, 2 and 3; and wherein any aforementioned alkyl, alkylene, alkenyl, cycloalkyl (including where an R8 and an R9 group together with an atom to which they are attached form a cycloalkyl ring), heterocycloalkyl (including where two R12 groups or an R12 group and an R13 group or an R8 and an R9 group together with an atom to which they are attached form a heterocycloalkyl ring), alkynyl, C(0)-alkyl, S(0)2-alkyl and benzyl is optionally substituted, where chemically possible, by 1 to 4 substituents which are each independently selected at each occurrence from the group consisting of: =0; =NRa, =NORa, C1-C4-alkyl, halo, nitro, cyano, C1-C4-haloalkyl, C2-C4-alkenyl, C2C4-alkynyl, NIRaRb, S(0)21Ra, S(0)1Ra, S(0)(NRIIRa, S(0)2N1RaR3 CO2Ra, C(0)Ra, CONRaRa, OR and SW; wherein Ra is independently selected from H and Cl-C4-alkyl; and Rb is independently selected from H, Ci-C4-alkyl, C(0)-Cra4-alkyl and S(0)2-Ci-C4-alkyl.
2. 2. A compound of claim 1, wherein n is 0.
3. 3. A compound of claim 1 or claim 2, wherein R2 is independently selected from Ci-C4-alkyl and C3-C6-cycloalkyl.
4. 4. A compound of any one of claims 1 to 3, wherein R3 is independently selected from H, C(0)R14, C(0)0R14, CH20C(0)R14 and CH20C(0)0R14.
5. 5. A compound of any one of claims 1 to 4, wherein R4 is H.
6. 6. A compound of any one of claims 1 to 3, wherein 53 and 54 together form a group independently selected from C1-C2-alkylene, -C(0)-and -C(S)-.
7. 7. A compound of any one of claims 1 to 6, wherein Y1 is 0.
8. 8. A compound of any one of claims 1 to 7, wherein m is 0.
9. 9. A compound of any one of claims 1 to 8, wherein X1 is S and X2 is N.
10. 10. A compound of any one of claims 1 to 8, wherein X1 is N and X2 is S.
11. 11. A compound of any one of claims 1 to 10, wherein ReisZlZ2Rea.
12. 12. A compound of claim 11, wherein Z1 is absent.
13. 13. A compound of claim 11 or claim 12, wherein Z2 is independently selected from NIR7, S, and 0.
14. 14. A compound of any one of claims 11 to 13, wherein Rba i R6b.
15. 15. A compound of claim 14, wherein R" has the structure: (515)x wherein x is an integer selected from 0, 1, 2, 3, 4 and 5.
16. 16. A compound of claim 1, wherein the compound of formula (I) is selected from: 42 Cl7NHHO 09 AlNHHO OGIN NH c2 %NH '\12 HO OeV11 0 9 NH \12 )HO ODINMe0 OAc \ (S HN -N 0Me0 OAcS-NMe0 OAcS-NMe0 OAcS-N\ ( HN Me0 OAc S -N 0 OMe OMe F and OMe
17. 17. A method for controlling fungal diseases, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound of any one of claims 1 to 16 to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.
18. 18. A use of a compound of any one of claims 1 to 16 to control fungal diseases of plants.
19. 19. A fungicidal composition comprising an effective and non-phytotoxic amount of an active compound of any one of claims 1 to 16.