WO2023247977A9

WO2023247977A9 - Deuterated picarbutrazox derivatives and their uses

Info

Publication number: WO2023247977A9
Application number: PCT/GB2023/051661
Authority: WO
Inventors: Bill Thompson; Alistair Miller; John Street
Original assignee: Redag Crop Protection Ltd
Priority date: 2022-06-24
Filing date: 2023-06-23
Publication date: 2024-03-07
Also published as: WO2023247977A1; GB202209321D0

Abstract

This invention relates to deuterated compounds useful in agriculture to treat diseases caused by oomycetes.

Description

DEUTERATED PICARBUTRAZOX DERIVATIVES AND THEIR USES

The present invention relates to deuterated oxime derivatives which are of use in the field of agriculture as fungicides.

Picarbutrazox, depicted below, is a known fungicide developed for use on commercially valuable crops, such soybean and cereals:

Picarbutrazox

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 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.

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.

Certain compounds of the invention may be as active or more active than prior art compounds, e.g, picarbutrazox. They may have activity against organisms which have developed a resistance to prior art compounds, e.g. picarbutrazox. However, certain embodiments of the present invention may also concern compounds which have a lower level of activity relative to 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. Certain compounds of the invention may be more selective than prior art compounds, e.g. picarbutrazox, 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. of the Invention

In a first aspect of the invention is provided a compound of formula (I):

agronomically acceptable salt or N-oxide thereof, wherein R¹ is independently selected from -CD3, -CHD2, CH2D and -CH3;

R² is independently at each occurrence selected from D and H; and

R³ is independently at each occurrence selected from -CD3, -CHD2, -CH2D and -CH3; wherein R¹, R² and R³ are selected so that at least one group selected from R¹, the two R² groups and the three R³ groups is D or comprises D.

The inventors of the present invention have found that compounds of Formula (I) exhibit a surprising increase in fungicidal and oomycetal activity in comparison to picarbutrazox.

Initial evidence also suggests that certain compounds of Formula (I) are more xylem-mobile than (non-deuterated) picarbutrazox meaning that they are more capable of being absorbed by the roots of a plant and distributed throughout the plant allowing the compound to kill, inhibit or prevent fungal or oomycete pathogens and stop the infection process in any part of the plant. In contrast, picarbutrazox is mainly phloem-mobile and may not be capable of reaching other parts of a plant when taken up by the roots. Compounds that are xylem- mobile can be used in ways that compounds with no or reduced xylem mobility, such as picarbutrazox, cannot. One such method is a soil drench which allows the treatment of diseases in all parts of the plant by application to the soil in which the plant grows. This often means that lower doses of the active compound are needed for targeted application via the roots compared with foliar administration for compounds with no or low xylem mobility. Soil drenching also allow plants to be simultaneously watered and avoids the need to separately administer the compound to the plant; application could also be via chemigation to high value crops grown in glasshouses.

In a second aspect of the invention there is provided a method for preventing, controlling or treating an agronomic disease caused by an oomycete, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound according to the first aspect of the invention to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

In a third aspect of the invention there is provided a method for preventing, controlling or treating a fungal disease, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound of the first aspect to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

In a fourth aspect of the invention there is provided a use of a compound of the first aspect to prevent, control or treat a disease caused by an oomycete in plants, crops or seeds.

In a fifth aspect of the invention there is provided a use of a compound of the first aspect to prevent, control or treat fungal disease in plants, crops or seeds.

In a sixth aspect of the invention there is provided an agrochemical formulation comprising an effective and non-phytotoxic amount of a compound of the first aspect.

In an embodiment, the compound of Formula (I) is a compound of Formula (II):

wherein R¹ and R² are as defined above for the compound of Formula (I) and wherein R¹ and R² are selected so that at least one group selected from R¹ and the two R² groups is D or comprises D. In an embodiment, the compound of Formula (I) is a compound of Formula (III):

wherein R¹ is independently selected from -CD3, -CHD2 and CH2D.

The following embodiments apply to compounds of Formulae (I), (II) or (III). 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 the compound of Formula (I), (II) or (III) is not in the form of an agronomically acceptable salt or /V-oxide. It may be that the compound of Formula (I), (II) or (III) is not in the form of an agronomically acceptable /V-oxide.

It may be that R¹ and R² are selected so that at least one group selected from R¹ and the two R² groups is D or comprises D.

It may be that R¹ is -CH3. It may be that R¹ is independently selected from -CD3, -CHD2 and CH2D3. Preferably, R¹ is -CD3.

It may be that at least one R² is D. It may be that R² is at each occurrence D. It may be that at least one R² is H. It may be that R² is at each occurrence H. It may be that one R² is D and one R² is H.

It may be that each R³ is -CH3. It may be that each R³ is independently selected from -CD3, - CHD2 and -CH2D. It may be that each R³ is -CD3. It may be that at least one R³ is -CH3. It may be that at least one R³ is selected from -CD3, -CHD2 and -CH2D. It may be that at least one R³ is -CD3. It may be that at least two R³ groups are -CH3. It may be that at least two R³ groups are selected from -CD₃, -CHD2 and -CH2D. It may be that at least two R³ groups are - CD₃.

The compound of Formula (I) may be a compound selected from:

The compound of formula (I) may be:

Detailed Description

The compounds of the present invention are oximes. Due to the C=N double bond of the oxime, geometric E/Z (or cis/trans) isomers are possible. The compound of formula (I) may therefore be the Z-isomer. The compound of formula (I) may be a mixture of the Z-isomer and the E-isomer. Alternatively, the compound of formula (I) may be the E-isomer. E/Z isomers may be separated by conventional techniques well known to those skilled in the art, for example, chromatography and fractional crystallisation.

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. Also included are acid addition or base salts wherein the counter ion is optically active, for example, D-lactate or L-lysine, or racemic, for example, DL-tartrate or DL-arginine.

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 /V-oxide.

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.

Unless stated otherwise, the present invention also includes all environmentally acceptable isotopically-labelled compounds of formula (I), 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 ¹¹C, ¹³C and ¹⁴C, nitrogen, such as ¹³N and ¹⁵N, and oxygen, such as ¹⁵0, ¹⁷O and ¹⁸O.

However, in the compounds of the invention, when a position is specifically designated as “D”, this position would be understood by a skilled person to be occupied by deuterium (²H) at an isotopic abundance greater than its natural isotopic abundance (e.g. greater than about 0.015%).

For example, a position designated “D” may be occupied with deuterium at an isotopic purity of ²H of greater than 50%. Isotopic purity can be determined using conventional analytical methods known to a person skilled in the art, such as mass spectrometry and nuclear magnetic resonance spectroscopy. A position designated “D” may be occupied with deuterium at an isotopic purity of ²H of at least 90%, e.g. at least 95%. A position designated “D” may be occupied with deuterium at an isotopic purity of ²H of at least 99%, e.g. at least 99.5%.

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.

Methods, Uses: Oomycete

The compounds of the invention are active against oomycetes.

According to an aspect of the present invention, there is provided a method for preventing, controlling or treating an agronomic disease caused by an oomycete, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound according to the first aspect of the invention to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

The active compounds can be applied neat, or in the form of a formulation. The compound 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). The compound may be applied as a drench or drip application (chemigation) to the soil in which the plant is growing.

The method may comprise applying an agronomically effective and substantially non- phytotoxic quantity of a compound according to the first aspect of the invention to seeds of plants.

The method may comprise applying an agronomically effective and substantially non- phytotoxic quantity of a compound according to the first aspect of the invention to soil in which plants are growing by drenching the soil with a formulation, e.g. an aqueous formulation, comprising the compound.

The compound may be applied at a dose of between 50 and 300 g/ha, e.g. 50 and 150 g/ha. The compound may be applied at a dose of between 70 and 0.1 g/ha. The compound may be applied at a dose of between 15 and 0.1 g/ha.

According to another aspect of the present invention, there is provided a use of a compound according to the first aspect of the invention to prevent, control or treat a disease caused by an oomycete in plants, crops or seeds.

The active compounds can be used neat, or in the form of a formulation.

The oomycete may be of the genus Phytophthora, Plasmopara, Pythium, Peronospora, Bremia, Albugo, Pseudoperonospora or Hyaloperonospora. The oomycete may be of the genus Phytophthora (e.g. Phytophthora infestans). The oomycete may be of the genus Plasmopara (e.g. Plasmopara obducens). The oomycete may be of the genus Pythium (e.g. Pythium ultimum).

The oomycete may be selected from the group consisting of Phytophthora infestans, Hyaloperonospora arabidopsidis, Phytophthora ramorum, Phytophthora sojae, Phytophthora capsica, Plasmopara viticola, Phytophthora cinnamomi, Phytophthora parasitica, Pythium ultimum, Albugo Candida, Bremia lactuca and Peronospora sparsa. Using common names, the disease to be prevented, controlled or treated may be late blight, downy mildew, sudden oak death, Ramorum disease, stem rot, root rot, fruit rot and/or white rust.

The following are further illustrative examples of disease that may be prevented, controlled or treated by the compounds of the present invention: 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 viticola',

Pseudoperonospora diseases, caused for example by Pseudoperonospora humuli or Pseudoperonospora cubensis', Pythium diseases, caused for example by Pythium ultimum.

The compounds of the invention may be active against a broad spectrum of oomycetes. Alternatively, they may be active specifically against certain oomycetes but not others. The compounds of the invention may therefore be active against a broad spectrum of oomycete diseases. Alternatively, they may be active specifically against certain oomycete diseases but not others.

Methods, Uses: Fungi

The compounds of the invention may also have activity as fungicides.

According to another aspect of the present invention, there is provided a method for preventing, controlling or treating a fungal disease, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound according to the first aspect of the invention to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

The compound 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). The compound may be applied as a drench or drip application (chemigation) to the soil in which the plant is growing. The method may comprise applying an agronomically effective and substantially non- phytotoxic quantity of a compound according to the first aspect of the invention to seeds of plants.

According to another aspect of the invention, there is provided a use of a compound according to the first aspect of the invention to prevent, control or treat fungal disease in plants, crops or seeds.

In addition 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 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 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.

Formulation

In a further aspect of the present invention there is provided an agrochemical formulation comprising an effective and non-phytotoxic amount of a compound according to the first aspect of the invention.

The formulation may further comprise one or more additional pesticides.

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 diseases present or liable to appear on 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 agrochemical formulation. This amount can be determined by systematic field trials, which are within the capabilities of a person skilled in the art.

The term “protecting” (in the context of protecting crops) is intended to cover both preventing disease prior to, or early in, the infection process as well as eradicating or controlling disease once the infection is widespread.

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 formulation may be a ready-to-use solution, emulsion, water- or oil-based suspension, powder, wettable powder, paste, soluble powder, dust, soluble granules, granules for broadcasting, suspoemulsion concentrate, natural substance impregnated with active compound, synthetic substance impregnated with active compound, fertilizer or a microencapsulation in polymeric substances. Application may be carried out, for example, by watering, spraying, atomizing, 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 seeds 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.

Formulations which could be used to administer compounds of the invention are outlined in Experiments 1-5.

Auxiliaries are substances which are suitable for imparting to the formulation 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 include 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 unsubstituted and substituted amines, amides, lactams (such as /V-alkylpyrrolidones) and lactones, the sulfones and sulfoxides (such as dimethylsulfoxide).

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 dimethylsulfoxide.

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 latices, 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 colorants 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 according to 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, acaricides, herbicides, insecticides, bactericides or other fungicides, 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 10 000 g/ha, preferably from 1 to 5 000 g/ha.

The formulations 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 formulation may be as described in the ‘Catalogue of pesticide formulation types and international coding system’ (Technical Monograph n° 2, 8th Edition by CropLife International).

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 oomycete 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.

The invention may be as described in one of the following numbered paragraphs:

wherein R¹ is independently selected from -CD3, -CHD2 and CH2D; or an agronomically acceptable salt or N-oxide thereof.

wherein R¹ is independently selected from -CD3, -CHD2 and CH2D. 3. A compound of paragraph 1 or paragraph 2, wherein R¹ is -CD3.

4. A method for preventing, controlling or treating a disease caused by an oomycete, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound of any one of paragraphs 1 to 3 to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

5. A method of paragraph 4, wherein the oomycete is of the genus Phytophthora.

6. A method of paragraph 4, wherein the oomycete is of the genus Plasmopara.

7. A method for preventing, controlling or treating a fungal disease, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound of any one of paragraphs 1 to 3 to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

8. A use of a compound of any one of paragraphs 1 to 3 to prevent, control or treat a disease caused by an oomycete in plants, crops or seeds.

9. A use of paragraph 8, wherein the oomycete is of the genus Phytophthora.

10. A use of paragraph 8, wherein the oomycete is of the genus Plasmopara.

11. A use of a compound of any one of paragraphs 1 to 3 to prevent, control or treat fungal disease in plants, crops or seeds.

12. An agrochemical formulation comprising an effective and non-phytotoxic amount of a compound selected from any one of paragraphs 1 to 3.

Description of Figures

Figure 1 shows the % control of Plasmopara obducens on Impatiens plants by Example 1 and picarbutrazox at doses of 30, 10 and 3 g/ha.

Figure 2 shows the % control of Plasmopara obducens on Impatiens plants by Example 1 and picarbutrazox in a glasshouse at doses of 62, 31 , 10, 3, 1 and 0.3 g/ha. Figure 3 shows the % control of Plasmopara obducens on Impatiens plants by Example 1 and picarbutrazox in a glasshouse at doses of 62, 125 and 250 g/ha 6, 3 and 1 day(s) before inoculation of the plants with Plasmopara.

Figure 4 shows the % control of Plasmopara obducens on Impatiens plants by Examples 1 , 2 and 3 and picarbutrazox in a glasshouse at doses of 10, 3, 1 and 0.3 g/ha.

Figure 5 shows the % control of Phytophthora infestans on tomato plants by Examples 1 , 2 and 3 and picarbutrazox after application via soil drench at doses of 10, 3, and 1 g/ha.

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, Wiley-VCH (1999 or later editions); "March's Advanced Organic Chemistry - Reactions, Mechanisms and Structure”, MB Smith, J. March, Wiley, (5th edition or later); “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); ("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 chemist will exercise his judgement and skill as to the most efficient sequence of reactions for 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:

LCMS - liquid chromatography-mass spectrometry

NMR - nuclear magnetic resonance

MS - mass spectrometry sat. - saturated Aq. - aqueous

Rt - room temperature

PDA - photodiode array

SQ - single quadruple

LIPLC - ultra performance liquid chromatography ha - hectare

Certain compounds of the invention can be synthesised according to any one of General Synthetic Schemes A, B or C below. Certain compounds of the invention can be synthesised according to or by methods analogous to the methods described in Examples 1 to 3.

General Synthetic Scheme

Scheme A

, wherein R¹ is independently selected from

Scheme B

wherein R¹ is independently selected from -CD3

independently at each occurrence selected from D and H, wherein R¹ and R² and R³ are selected so that at least one group selected from R¹ and the two R² groups is D or comprises

, wherein R¹ is independently selected from -CD3, -CHD2, CH2D and -CH3.

Analytical Procedures

Mass spectra were run on LC-MS systems using electrospray ionization. These were run using a Waters Acquity Classic LIPLC with PDA and SQ mass detection (LC-MS-1) or a Waters Acquity H-Class LIPLC with PDA and QDA mass detection (LC-MS-2). [M+H]⁺ refers to mono-isotopic molecular weights.

LC-MS-1 Method 2B

Column: Acquity UPLC BEH C18 2.1 x 50 mm 1.7 pm

Column Temp: 50 °C

Flow rate: 0.8 mL/min.

Eluents: A: H2O, 0.1 % ammonia B: MeCN

Gradient: 0.0-1.8 mins 2-98% B; 1.8-2.1 mins 98% B; 2.1-2.5 mins 98% A. LC-MS-2 Method 2B

Column: Acquity UPLC BEH C182.1 x 50 mm 1.7 pm

Column Temp: 50 °C

Flow rate: 0.8 mL/min.

Eluents: A: H2O, B: MeCN, C: 50% H2O I 50% MeCN + 2.0% ammonia (aq.)

Gradient: 0.0-1.7 mins 0-95% B, 5% C; 1.7-2.1 mins 95% B, 5% C; 2.1-2.5 mins 95% A, 5% C.

NMR spectra were run on either a Bruker Ultrashield 400 MHz or 500MHz NMR spectrometer. Spectra were recorded at 298K and were referenced using the solvent peak.

Synthetic Intermediates

Intermediate X3 that may be used in the synthesis of certain compounds of the invention can be made according to the following scheme:

Intermediate X1 : 1-(Methyl-d3-amino)-2-phenyl-1,2-ethanedione

To a solution of methyl phenylglyoxylate (1.67 g, 10.17 mmol) in methanol (10.2 mL) was added a solution of methyl-ds-amine hydrochloride (933 mg, 13.22 mmol) in methanol (6.0 mL) followed by triethylamine (1.84 mL, 13.22 mmol). The reaction mixture was then stirred at ambient temperature for 20 hours and then concentrated in vacuo. The residue was partitioned between EtOAc (50 mL) and water (25 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (4 x 50 mL). The combined organic phases were washed with sat. brine (75 mL), dried over MgSO4, filtered and concentrated to give a yellow oil (1.8 g). Chromatography on SiO2 (25 g cartridge) eluting with 0-30 % EtOAc I petroleum ether gave the title compound as a white solid (1.15 g).

LC-MS-2 (Method 2B): Rt 1.07 mins; MS m/z 167.1 = [M+H]⁺ (100% @ 254 nm). ¹H NMR (500 MHz, Chloroform-d) 5 8.40 - 8.29 (m, 2H), 7.67 - 7.58 (m, 1H), 7.53 - 7.44 (m, 2H), 7.07 (s, 1 H).

Intermediate X2: ( 1-Methyl-ch- 1H-1,2,3, 4-tetrazol-5-yl)phenylformaldehyde

To a solution of 1-(methyl-d3-amino)-2-phenyl-1,2-ethanedione (Intermediate X1) (1.0 g, 6.02 mmol) in chloroform (8 mL), was added dimethylformamide (47 pL, 0.6 mmol) followed by thionyl chloride (658 pL, 9.03 mmol) dropwise. The reaction mixture was heated to reflux for 5 hours and then concentrated in vacuo. The residue was concentrated from toluene (2 * 10 mL), dissolved in toluene (30 mL) and added dropwise to a mixture of sodium azide (469 mg, 7.22 mmol) and tetrabutylammonium bromide (97 mg, 0.30 mmol) in toluene (10 mL) and water (10 mL). The reaction mixture was stirred at ambient temperature overnight and then partitioned between EtOAc (100 mL) and water (50 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (2 x 50 mL). The combined organic phases were dried over MgSO4, filtered and concentrated to give a colourless oil (1.02 g). Chromatography on SiO2 (25 g cartridge) eluting with 0-20 % EtOAc I petroleum ether gave the title compound as a white solid (928 mg).

LC-MS-2 (Method 2B): Rt 1.25 mins; MS m/z 191.0 = [M+H]⁺ (100% @ 254 nm).

¹H NMR (500 MHz, Chloroform-d) 5 8.50 - 8.43 (m, 2H), 7.75 - 7.69 (m, 1H), 7.58 (t, J = 7.8 Hz, 2H).

Intermediate X3: (1-Methyl-d3-1H-1,2,3,4-tetrazol-5-yl)phenylmethanone oxime

To a solution of (1-methyl-d3-1 H-1 ,2,3,4-tetrazol-5-yl)phenylformaldehyde (Intermediate X2) (900 mg, 4.71 mmol) in pyridine (8.6 mL), was added hydroxylamine hydrochloride (818 mg, 11.77 mmol). The reaction mixture was heated to 45 °C for 18 hours and then cooled to room temperature before being diluted with water (70 mL) and EtOAc (140 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (2 x 70 mL). The combined organic phases were dried over MgSCU, filtered and concentrated in vacuo to give a colourless oil (1.37 g). Chromatography on SiC>2 (12 g cartridge) eluting with 10-40% EtOAc I petroleum ether gave the title compound as a white solid (955 mg).

LC-MS-2 (Method 2B): Rt 0.96 mins; MS m/z 207.1 = [M+H]⁺ (100% @ 254 nm).

¹H NMR (500 MHz, Chloroform-d) 5 8.74 (s, 1 H), 7.54 - 7.49 (m, 2H), 7.47 - 7.42 (m, 1 H), 7.42 - 7.36 (m, 2H).

Intermediate X4: (6-Amino-2-pyridyl)methanol-d2

To a solution of methyl 6-aminopyridine-2-carboxylate (200 mg, 1.31 mmol) in tetrahydrofuran (3 mL) at 0 °C, was added lithium aluminium deuteride (166 mg, 3.94 mmol). The reaction mixture was stirred at 0 °C for 5 minutes before being allowed to warm to ambient temperature. After 18 hours, the reaction mixture was diluted with Et20 (2 mL), cooled to 0 °C and quenched by dropwise addition of D2O (170 pL), aq. NaOH (170 pL, 2M) and H2O (0.5 mL). After the mixture warmed to ambient temperature it was diluted with Et20 and filtered. The filtrate was concentrated in vacuo and the residue was concentrated from toluene (2 x 10 mL) to give an oily residue (0.14 g). Chromatography on SiC>2 (12 g cartridge) eluting with 0.5-5.0% MeOH I CH2CI2 gave the title compound as a white solid (97 mg).

LC-MS-2 (Method 2B): Rt 0.49 mins; MS m/z 126.9 = [M+H]⁺ (14% @ 254 nm).

¹H NMR (400 MHz, Chloroform-d) 5 7.42 (t, J = 7.7 Hz, 1 H), 6.57 (d, J = 7.3 Hz, 1 H), 6.39 (d, J = 8.1 Hz, 1 H), 4.48 (br. s, 2H), 2.81 (br. s, 1 H).

Intermediate X5: 6-r(tert-Butoxycarbonyloxy)methyl-d21-2-pyridylamino 2,2- dimethylpropionate

To a solution of (6-Amino-2-pyridyl)methanol-d2 (Intermediate X4) (97 mg, 0.77 mmol) in tertbutanol (3.9 mL) at 25 °C, was added di-tert-butyl dicarbonate (223 mg, 1.02 mmol) followed by 4-dimethylaminopyridine (9 mg, 0.08 mmol). The reaction mixture was stirred at 25 °C for 2.5 hours and then additional di-tert-butyl dicarbonate (223 mg, 1.02 mmol) was added. The reaction mixture was stirred at 25 °C for 18 hours and then concentrated in vacuo. The residue was concentrated from EtOAc (2 x 5 mL) to give a yellow oil (0.3 g). Chromatography on SiC>2 (4 g cartridge) 2-15 % EtOAc I petroleum ether gave the title compound as a colourless oil (142 mg).

LC-MS-2 (Method 2B): Rt 1.79 mins; MS m/z 327.1 = [M+H]⁺ (93% @ 254 nm).

¹H NMR (400 MHz, Chloroform-d) 5 7.85 (d, J = 8.4 Hz, 1 H), 7.66 (t, J = 7.9 Hz, 1 H), 7.23 (br. s, 1 H), 7.02 (d, J = 7.4 Hz, 1 H), 1.51 (s, 9H), 1.50 (s, 9H).

Intermediate X6: 6-(Hvdroxymethyl-d2)-2-pyridylamino 2,2-dimethylpropionate

To a solution of 6-[(terf-Butoxycarbonyloxy)methyl-d2]-2-pyridylamino 2,2-dimethylpropionate (Intermediate X5) (142 mg, 0.44 mmol) in Water (1.3 mL) and Methanol (3.6 mL) at ambient temperature, was added lithium hydroxide monohydrate (91 mg, 2.18 mmol). The reaction mixture was stirred at ambient temperature for 17 hours and then concentrated to remove the organic solvent. After dilution with water (10 mL), the product was extracted with CH2CI2 (3 x 10 mL). The combined organic phases were dried over MgSCU, filtered and concentrated in vacuo to give the title compound as a pale pink oil (86 mg).

LC-MS-2 (Method 2B): Rt 1.25 mins; MS m/z 227.0 = [M+H]⁺ (100% @ 254 nm).

¹H NMR (400 MHz, Chloroform-d) 5 7.82 (d, J = 8.3 Hz, 1 H), 7.65 (t, J = 7.9 Hz, 1 H), 6.89 (d, J = 7.4 Hz, 1 H), 3.35 (br. s, 1 H), 1.53 (s, 9H).

Intermediate X7: 6-(Bromomethyl-d2)-2-pyridylamino 2,2-dimethylpropionate

To a solution of 6-(Hydroxymethyl-d2)-2-pyridylamino 2,2-dimethylpropionate (Intermediate X6) (80 mg, 0.35 mmol) in dichloromethane (0.7 mL) at 0 °C, was added carbon tetrabromide (188 mg, 0.57 mmol) followed by triphenylphosphine (111 mg, 0.42 mmol). The reaction mixture was stirred at 0 °C for 2 hours and then concentrated in vacuo. Chromatography on SiC>2 (4 g cartridge) eluting with 2-10% EtOAc I petroleum ether gave the title compound as a colourless oil (80 mg).

LC-MS-2 (Method 2B): Rt 1.65 mins; MS m/z 287.1 = [M-H]’ (100% @ 254 nm).

¹H NMR (400 MHz, Chloroform-d) 5 7.85 (d, J = 8.4 Hz, 1H), 7.64 (t, J = 7.9 Hz, 1 H), 7.05 (d, J = 7.4 Hz, 1 H), 1.51 (s, 9H).

To a suspension of sodium hydride (42 mg, 1.05 mmol, 60% purity) in dimethylformamide (0.9 mL) at 0 °C, was added a solution of (1-methyl-d3-1H-1,2,3,4-tetrazol-5- yl)phenylmethanone oxime (Intermediate X3) (80 mg, 0.39 mmol) in dimethylformamide (0.75 mL) dropwise. The mixture was stirred at 0 °C for 50 minutes and then a solution of tert-butyl N-[6-(bromomethyl)-2-pyridyl]carbamate (123 mg, 0.43 mmol) in dimethylformamide (0.75 mL) was added dropwise. The reaction mixture was stirred at 0 °C for 15 minutes and then allowed to warm to ambient temperature. After 70 minutes, the reaction mixture was added to a sat. aq. NH4CI solution (10 mL) and the product was extracted with EtOAc (3 x 10 mL). The combined organic phases were washed with brine (10 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was concentrated from toluene (2 x 5 mL) to give an off-white oily residue. Chromatography on SiO2 (12 g cartridge) 2-35% EtOAc I petroleum ether gave the title compound as a white solid (132 mg).

LC-MS-2 (Method 2B): Rt 1.79 mins; MS m/z 413.2 = [M+H]⁺ (100% @ 254 nm). ¹H NMR (400 MHz, Chloroform-d) 5 7.88 (d, J = 8.3 Hz, 1H), 7.66 (t, J = 7.9 Hz, 1 H), 7.54 - 7.47 (m, 2H), 7.47 - 7.42 (m, 1 H), 7.41 - 7.33 (m, 2H), 6.93 (d, J = 7.4 Hz, 1H), 5.25 (s, 2H), 1.52 (s, 9H).

Example 2: _ tert-butyl (Z)-(6-(((((1-(methyl-d3)-1H-tetrazol-5- yl)( henyl)methylene)amino)oxy)methyl-d2) yridin-2-yl)carbamate

To a suspension of sodium hydride (13 mg, 0.33 mmol, 60% purity) in dimethylformamide (0.3 mL) at 0 °C, was added a solution of (1-methyl-d3-1H-1,2,3,4-tetrazol-5- yl)phenylmethanone oxime (Intermediate X3) (25 mg, 0.12 mmol) in dimethylformamide (0.21 mL) dropwise. The mixture was stirred at 0 °C for 40 minutes and then a solution of 6- (Bromomethyl-d2)-2-pyridylamino 2,2-dimethylpropionate (Intermediate X7) (39 mg, 0.13 mmol) in dimethylformamide (0.21 mL) was added dropwise. The reaction mixture was stirred at 0 °C for 10 minutes and then allowed to warm to ambient temperature. After 1 hour, the reaction mixture was added to a sat. aq. NH4CI solution (5 mL) and the product was extracted with EtOAc (3 * 10 mL). The combined organic phases were washed with brine (10 mL), dried over MgSCU, filtered and concentrated in vacuo. The residue was concentrated from toluene (2 x 10 mL) to give an off-white oily residue. Chromatography on SiC>2 (4 g cartridge) 2-20% EtOAc I petroleum ether followed by lyophilization gave the title compound as a white solid (9 mg).

LC-MS-2 (Method 2B): Rt 1.74 mins; MS m/z 415.1 = [M+H]⁺ (100% @ 254 nm).

¹H NMR (400 MHz, Chloroform-d) 5 7.88 (d, J = 8.4 Hz, 1 H), 7.66 (t, J = 7.9 Hz, 1 H), 7.54 - 7.48 (m, 2H), 7.47 - 7.41 (m, 1H), 7.41 - 7.34 (m, 2H), 6.94 (d, J = 7.4 Hz, 1 H), 1.52 (s, 9H).

Example _ 3; _ tert-butyl _ (Z)-(6-(((((1-methyl- 1 H-tetrazol-5- yl)(phenyl)methylene)amino)oxy)methyl-d2)pyridin-2-yl)carbamate

To a suspension of sodium hydride (13 mg, 0.33 mmol, 60% purity) in dimethylformamide (0.3 mL) at 0 °C, was added a solution of (1-methyl-1/7-1 ,2,3,4-tetrazol-5- yl)phenylmethanone oxime (25 mg, 0.12 mmol) in dimethylformamide (0.21 mL) dropwise. The mixture was stirred at 0 °C for 45 minutes and then a solution of 6-(Bromomethyl-d2)-2- pyridylamino 2,2-dimethylpropionate (Intermediate X7) (39 mg, 0.13 mmol) in dimethylformamide (0.21 mL) was added dropwise. The reaction mixture was stirred at 0 °C for 10 minutes and then allowed to warm to ambient temperature. After 55 minutes, the reaction mixture was added to a sat. aq. NH4CI solution (5 mL) and the product was extracted with EtOAc (3 * 10 mL). The combined organic phases were washed with brine (10 mL), dried over MgSCU, filtered and concentrated in vacuo. The residue was concentrated from toluene (2 x 10 mL) to give an off-white oily residue. Chromatography on SiC>2 (4 g cartridge) 2-30% EtOAc I petroleum ether followed by lyophilization gave the title compound as a white solid (20 mg).

LC-MS-2 (Method 2B): Rt 1.74 mins; MS m/z 412.2 = [M+H]⁺ (100% @ 254 nm).

¹H NMR (400 MHz, Chloroform-d) 5 7.88 (d, J = 8.4 Hz, 1 H), 7.66 (t, J = 7.9 Hz, 1 H), 7.53 - 7.48 (m, 2H), 7.47 - 7.41 (m, 1 H), 7.40 - 7.34 (m, 2H), 6.94 (d, J = 7.4 Hz, 1 H), 3.97 (s, 3H), 1.52 (s, 9H).

Biological Activity

The activity of Examples 1 to 3 was assessed by testing against certain oomycete plant pathogens.

Experiment 1: Initial experiment

Picarbutrazox and Example 1 were screened at three concentrations (30, 10 and 3 g/ha) for efficacy against Plasmopara obducens, the causal agent of impatiens downy mildew.

Treatments were applied to 5-week-old impatiens (var. Lollipop White) grown in 9 cm diameter pots. Each plant was sprayed with 2 mL of the test compound formulated in a 25% acetone and 75% 0.1% Tween 20 solution. Treatments were applied using handheld atomiser sprayers.

Each treatment was replicated three times with treatments applied 24 h prior to inoculation with sporangia of P. obducens. Treated, and the appropriate control plants, were inoculated with 2 ml of a 1x10⁴ sporangia/ml spore suspension and then incubated in the dark at 5°C overnight.

Plants were transferred to a glasshouse and assessed for disease symptoms 14 days after inoculation. Control (%) was based on the number of leaves out of 15 showing sporulation on the underside of the leaves compared to the untreated controls.

As can be seen from Figure 1 , Example 1 provides greater control over Plasmopara at the lowest tested dose.

Experiment 2: Plasmopara on Impatiens plants at doses between 0.3 and 62 g/ha

Picarbutrazox and Example 1 were screened at six concentrations (62, 31, 10, 3, 1 and 0.3 g/ha) for efficacy against Plasmopara obducens, the causal agent of impatiens downy mildew.

Treatments were applied to 5-week-old impatiens (var. Lollipop White) grown in 9 cm diameter pots. Plants were treated using a track sprayer in a spray volume of 200 L/ha. Test compounds were formulated in a 25% acetone and 75% 0.1% Tween 20 solution.

Each treatment was replicated five times with treatments applied 24 h prior to inoculation with sporangia of P. obducens. Treated, and the appropriate control plants, were inoculated with 2 ml of a 1x10⁴ sporangia/ml spore suspension and then incubated in the dark at 5°C overnight.

Plants were transferred to a glasshouse and assessed for disease symptoms 14 days after inoculation. Control (%) was based around a count of the number of leaves per replicate plant expressing sporulation caused by P. obducens on the underside of the leaves compared to the untreated controls. In this experiment, the inoculated control had a total number of 13.80 infected leaves.

As can be seen from Figure 2, at the lowest tested dose of 0.3 g/ha, Example 1 provided superior control of Plasmopara over picarbutrazox.

Experiment 3: Plasmopara - Commercial doses Picarbutrazox and Example 1 were screened at three concentrations (250, 125 and 62 g/ha) and three pre-inoculation treatment timings (1 , 3 and 6 days) for efficacy against Plasmopara obducens, the causal agent of impatiens downy mildew.

Each treatment was replicated three times with treatments applied either 1 , 3 or 6 days prior to inoculation with sporangia of P. obducens. Treated, and the appropriate control plants, were inoculated with 2 ml of a 1x10⁴ sporangia/ml spore suspension and then incubated in the dark at 5°C overnight.

Plants were transferred to a glasshouse and assessed for disease symptoms 14 days after inoculation. Control (%) was based around a count of the number of leaves per replicate plant expressing sporulation caused by P. obducens on the underside of the leaves compared to the untreated controls.

As can be seen from Figure 3, at 1 day before inoculation, Example 1 provided better control of Plasmopara than picarbutrazox, especially at doses of 62 and 125 g/ha.

On the basis of Experiment 3, the effective control of Plasmopara by Example 1 vs picarbutrazox at likely commercial doses was confirmed with increased efficacy apparent (90% and 49% disease control for Example 1 compared to 57% and 18% for picarbutrazox at doses of 125 and 62 g/ha, respectively).

Experiment 4: Plasmopara on Impatiens plants at doses between 0.3 and 10 g/ha

Picarbutrazox and Examples 1 to 3 were screened at four concentrations (10, 3, 1 and 0.3 g/ha) for efficacy against Plasmopara obducens, the causal agent of impatiens downy mildew.

Plants were transferred to a glasshouse and assessed for disease symptoms 14 days after inoculation. Control (%) was based around a count of the number of leaves per replicate plant expressing sporulation caused by P. obducens on the underside of the leaves compared to the untreated controls. In this experiment, the inoculated control had a total number of 44.75 infected leaves.

As can be seen from Figure 4, at doses of 0.3 g/ha, Examples 1 provided improved control of Plasmopara compared to picarbutrazox. At 1 g/ha Examples 1 and 3 provided improved control compared to picarbutrazox.

Based on the aforementioned experiments, the compounds of the present invention display improved control over the tested pathogens when compared to picarbutrazox at certain doses. Often, the compounds of the present invention display improved control over the tested pathogens at the lowest tested doses when compared to picarbutrazox. This means that less compound needs to be applied to the target area in order to elicit similar levels of control achieved by higher doses of picarbutrazox. The compounds of the present invention therefore provide a more environmentally friendly and cost-effective pathogen control than picarbutrazox.

Experiment 5: Soil drench In planta test

Picarbutrazox and Examples 1 to 3 were screened at three concentrations (10, 3, and 1 g/ha) for efficacy against Phytophthora infestans on tomato plants. Treatments were applied to 3-week-old tomato plants grown in 9 cm diameter pots (1 plant per pot). Compounds were solubilised in DMSO and diluted to give a 0.02 % DMSO treatment solution using 0.1% Tween 20. Treatments were applied as a drench with 10 ml of treatment solution applied across the surface of each replicate pot.

Each treatment was replicated three times with treatments applied 48 h prior to inoculation with sporangia of Phytophthora infestans. Treated and the appropriate control plants were inoculated with 1 ml of a spore suspension at 1x10⁴ spores/ml. Inoculated plants were kept under high humidity conditions for 5 days and then assessed for disease. Disease severity was assessed as a percentage of the whole plant.

Figure 5 shows the % control of the disease. The % control was calculated based on the disease severity of the control. As can be seen from Figure 5, Example 2 provides superior disease control at 10 and 3 g/ha compared to picarbutrazox. Experiment 5 therefore provides evidence that certain compounds of the invention may be more xylem-mobile than picarbutrazox since to control the disease in the inoculated plants after application via a soil drench a compound must be absorbed by the roots of the plant and move through the plants xylem to treat the infection.

Claims

1 . A compound of formula (I):

R² is independently at each occurrence selected from D and H; and

2. A compound of claim 1 , wherein R¹ is -CD3.

3. A compound of claim 1 , wherein R¹ is -CH3.

4. A compound of any preceding claim, wherein R² is at each occurrence D.

5. A compound of any one of claims 1 to 3, wherein R² is at each occurrence H.

6. A compound of any preceding claim, wherein R³ is at each occurrence CH3.

7. A compound of any one of claims 1 to 5, wherein R³ is at each occurrence CD3.

8. A compound of claim 1 , wherein the compound of Formula (I) is a compound selected from:

9. A method for preventing, controlling or treating a disease caused by an oomycete, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound of any one of claims 1 to 8 to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

10. A method of claim 9, wherein the oomycete is of the genus Phytophthora.

11. A method of claim 9, wherein the oomycete is of the genus Plasmopara.

12. A method for preventing, controlling or treating a fungal disease, the method comprising applying an agronomically effective and substantially non-phytotoxic quantity of a compound of any one of claims 1 to 8 to seeds of plants, to plants themselves or to an area where it is intended that plants will grow.

13. A use of a compound of any one of claims 1 to 8 to prevent, control or treat a disease caused by an oomycete in plants, crops or seeds.

14. A use of claim 13, wherein the oomycete is of the genus Phytophthora.

15. A use of claim 13, wherein the oomycete is of the genus Plasmopara.

16. A use of a compound of any one of claims 1 to 8 to prevent, control or treat fungal disease in plants, crops or seeds.

17. An agrochemical formulation comprising an effective and non-phytotoxic amount of a compound selected from any one of claims 1 to 8.