Carboxamide apyrase inhibitors

Abstract

Disclosed herein are apyrase inhibitors of Formula (I): (I). Also disclosed herein are methods for using the disclosed inhibitors, including in methods for protecting crops from pests. In one aspect the apyrase inhibitors are useful for enhancing the activity of pesticides for the protection of crops from pathogens and to support crop yield.

Description

[0001] CARBOXAMIDE APYRASE INHIBITORS

[0002] CROSS-REFERENCE

[0003] This application claims the benefit of the earlier filing date of U.S. Provisional Application No.

[0004] 63 / 559.782, filed February 29, 2024. the disclosure of which is incorporated herein by reference.

[0005] FIELD

[0006] The present disclosure relates to inhibitors of apyrase and methods for their use, in particular in the treatment of crops susceptible to pathogens.

[0007] BACKGROUND

[0008] Crops are plagued worldwide by a variety of pests. These pests, such as insects, mites, nematodes, weeds and fungi, have developed an array of mechanisms for surviving pesticides, such as by sequestering, exporting or detoxifying them. The present inventors have discovered molecules and methods for potentiating the efficacy of pesticides by blocking certain mechanisms of resistance.

[0009] SUMMARY

[0010] Disclosed herein are molecules and methods for their use in supporting crop viability and yield, by. for example, protecting crops from pests. In one embodiment, disclosed herein is a method for inhibiting apyrase enzy mes, comprising contacting the apyrase with a compound of the formula , wherein wherein R1, R2, R;. R4, Z and n are as described herein.

[0011] In further embodiments, an apyrase inhibitor as described herein is used in combination with one or more pesticides to treat a crop at risk of disease.

[0012] The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description. DETAILED DESCRIPTION

[0013] I. Terms

[0014] The following explanations of terms and methods are provided to better describe the present disclosure and to guide those of ordinary skill in tire art in the practice of the present disclosure. The

[0015] 5 singular forms “a,” “an,” and “the” refer to one or more than one, unless the context clearly dictates otiierwise. The term “or” refers to a single element of stated alternative elements or a combination of two or more elements, unless the context clearly indicates othenvise. As used herein, “comprises” means “includes.” Thus, “comprising A or B,” means “including A, B, or A and B,” without excluding additional elements. Ail references, including patents and patent applications cited herein, are

[0016] 10 incorporated by reference in their entirety, unless otiierwise specified.

[0017] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, percentages, temperatures, times, and so forth, as used in the specification or claims, are to be understood as being modified by the term “about.” Accordingly, unless othenvise indicated, implicitly or explicitly, the numerical parameters set forth are approximations that may depend on the desired properties sought

[0018] 15 and / or limits of detection under standard test conditions / methods. When directly and explicitly distinguishing embodiments from discussed prior art, the embodiment numbers are not approximates unless the word “about” is expressly recited.

[0019] Unless explained otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Although

[0020] 20 methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting.

[0021] “Administering” refers to any suitable mode of administration, to control a fungal pathogen, including, treatment of an extant crop, seeds, soil or combination thereof.

[0022] 25 “Control” with reference to a fungal pathogen, means block, inhibit and / or eradicate a fungal pathogen and / or prevent the fungal pathogen from damaging a crop. In one embodiment, control refers to the reduction of one or more fungi to undetectable levels, or to the reduction or suppression of a fungus to acceptable levels as determined by one of ordinary skill in the art (for example, a crop grower). Determinations of acceptable levels of fungus reduction are based on a number of factors, including to

[0023] 30 the crop, pathogen, severity of the pathogen, use restrictions, economic thresholds and other factors known to those of ordinary skill in the art.

[0024] As used herein, the terms “enhancer” and "potentiator", refer to a compound or compounds disclosed herein that enhance the effects of a pesticide. Without limitation to theory the present enhancer compounds disclosed herein may function by blocking one or more pathways by which a pathogen, such

[0025] 2 as a fungal pathogen, evades toxicity, such as by detoxifying, sequestering or transporting a pesticide. In certain embodiment, the present compounds inhibit enzymatic apyrase activity which leads to the enhancement, accentuation or potentiation of a pesticide, such as an acaricide, antimicrobial, fungicide, herbicide, insecticide, molluscicide and / or nematocide. For example, when the enhancer or potentiator is

[0026] 5 used in conjunction with a fungicide, the combination of the potentiator and the fungicide enhances the fungicidal effect of the fungicide and / or renders a fungus that has become resistant to the fungicide susceptible to the fungicide as a result of the activity of the potentiator. Most often, these enhancers or potentiators do not themselves inhibit the growth of a fungus itself, nor do they have a detrimental effect on a living organism that is (or could be) infected with a fungus.

[0027] 10 As used herein, the term "inoculation" refers to a method used to administer or apply an effective amount of a disclosed compound or formulation thereof to a target area of a field and / or plant. The inoculation method can be, but is not limited to, aerosol spray, pressure spray, direct watering, and dipping. Target areas of a plant could include, but are not limited to, the leaves, roots, stems, buds, flowers, fruit, seed of the plant, and bulbs of the plant including bulb, corm, rhizoma, stem tuber, root

[0028] 15 tuber and rhizophore. Inoculation can include a method wherein a plant is treated in one area (for example, the root zone or foliage) and another area of the plant becomes protected (for example, foliage is inoculated when a disclosed compound is applied in the root zone or new growth when applied to foliage).

[0029] As used herein, the terms "wettable granule", "water dispersible granule", and "dispersible

[0030] 20 granule" refer to a solid granular formulation prepared by a granulation process, optionally containing fine particles of polymer-associated acti ve ingredient, or aggregates of the same, a wetting agent and / or a dispersant, and optionally an inert filler. Wettable granules can be stored as a formulation, and can be provided to the market and'or end user without further processing. In some embodiments, they can be placed in a water-soluble bag for ease of use by the end user. In practical application, wettable granules

[0031] 25 are prepared for application by tire end user. The wettable granules are mixed with water in the end user's spray tank to the proper dilution for the particular application. Dilution can vary by crop, target pathogen, time of year, geography, local regulations, and intensity of infection or pathogen load among other factors. Once properly diluted, the solution can be applied by spraying

[0032] As used herein, the terms "wettable powder", "water dispersible powder", and "dispersible

[0033] 30 powder", refer to a solid pow'dered formulation that contains active ingredient, optionally associated with a polymer, or aggregates of the same, and optionally one or more of a dispersant, a wetting agent, and an inert filler. Wettable powders can be stored as a formulation, and can be provided to the market and / or end user without further processing. In some embodiments, they can be placed in a water-soluble bag for ease of use by the end user. In practical application, a wettable pow der is prepared for application by tire

[0034] 3 end user. The wettable powder is mixed with water in the end user's spray tank to the proper dilution for the particular application. Dilution can vary by crop, fungal pathogen, time of year, geography, local regulations, and intensity of fungal load, among other factors. Once properly diluted, the solution can be applied by spraying.

[0035] 5 As used herein, the term "high solids liquid suspension" refers to a liquid formulation that contains fine particles of active ingredient, or fine polymer particles associated with active ingredient, or aggregates of the same, a wetting agent and / or a dispersant, an anti-freezing agent, optionally an anti- settling agent or thickener, optionally a preservative, and water or oil as a carrier. High solids liquid suspensions can be stored as a formulation, and can be provided to the market and / or end user without

[0036] 10 further processing. In practical application, high solids liquid suspensions are prepared for application by the end user. The high solids liquid suspensions are mixed with water or oil in the end user's spray tank to tire proper dilution for the particular application. Dilution can vary by crop, fungal pathogen, time of year, geography, local regulations, and intensity of infection among other factors. Once properly diluted, the solution can be applied by spraying.

[0037] 15 As used herein, the term "phytologically acceptable" refers to compositions, diluents, excipients, and / or carriers that are generally applicable for use with any part of a plant during any part of its life cycle, including but not limited to seeds, seedlings, plant cells, plants, or flowers. The compositions can be prepared according to procedures, methods and formulas that are known to those of skill in the agricultural arts. Following the teachings of the present disclosure the artist skilled in the agricultural

[0038] 20 and / or chemical arts can readily prepare a desired composition. Most commonly, the compounds disclosed herein can be formulated to be stored, and / or applied, as aqueous or non-aqueous suspensions or emulsions prepared neat or from concentrated formulations of the compositions. Alternatively tire compounds disclosed herein can be formulated for use in aerosol -generating equipment for application to agricultural produce stored in sealed chambers - an application method known as fogging. Water-

[0039] 25 soluble, water-suspendable or emulsifiable formulations comprising the presently disclosed compounds can also be convened into or formulated as solids (for example, wettable powders), which can then be diluted into a final formulation. Tn certain formulations, the compositions of the present disclosure can also be provided in growth media, such as in vitro media for growth of plant or other types of cells, in laboratory plant growth media, in soil, or for spraying on seeds, seedlings, roots, stems, stalks, leaves,

[0040] 30 flow ers or the entire plant.

[0041] Compounds herein can include all stereoisomers, including E and Z isomers, enantiomers, diastereomers, mixtures, racemates, atropisomers, and tautomers thereof.

[0042] Non-limiting examples of optional substituents include hydroxyl groups, sulfhydryl groups, halogens, amino groups, nitro groups, nitroso groups, cyano groups, azido groups, sulfoxide groups,

[0043] 4 sulfone groups, sulfonamide groups, carboxyl groups, carboxaldehyde groups, imine groups, alkyl groups, halo-alkyl groups, alkenyl groups, haloalkenyl groups, alkynyl groups, halo-alkynyl groups, alkoxy groups, aryl groups, aryloxy groups, aralkyl groups, arylalkoxy groups, heterocyclylalky! groups, heteroaryl groups, cycloalkyl groups, acyl groups, acyloxy groups, carbamate groups, amide groups,

[0044] 5 ureido groups, epoxy groups, and ester groups.

[0045] “Alkyl” refers to an optionally substituted straight-chain, or optionally substituted branched-chain saturated hydrocarbon. Non-limiting examples of alkyl groups include straight, branched, and cyclic alkyl and alkylene groups. An alkyl group can be, for example, a C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C-20, C-21, C22, C23, C24, C25, C26, C27, C28, C29, C-30, C31, C32, C33,

[0046] 10 C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, C47, C48, C49, or C50 group that is substituted or unsubstituted. In some cases alkyd refers to a group having from one to about ten carbon atoms, or from one to six carbon atoms, wherein an sp3-hybridized carbon of the alkyl residue is attached to the rest of the molecul e by a singl e bond. Whenever it appears herein, a numerical range such as “C1-6 alkyl” means that the alkyl group consists of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5

[0047] 15 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, the alkyl is a C1-10 alkyl, a C1-9 alkyl, a C1-8 alkyl, a C1-7 alkyl, a C1-6 alkyl, a C1-5 alkyl, a C1-4 alkyl, a C1-3 alkyl, a C1-2 alkyl, or a C1 alkyd.

[0048] Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-

[0049] 20 methy 1-1 -propyl, 2-methyl-2-propyl, 2-methyl-1 -butyl, 3-methyl-1 -butyl, 2-methyd-3-butyd, 2,2- dimethyl-1 -propyl, 2-methyl-1 -pentyl, 3-methyl-1 -pentyl, 4-methyl-1 -pentyl, 2-methyl-2-pentyl, 3- methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1 -butyl, 3,3-dimethyl-1 -butyl, 2-ethyl-l-buty 1, n-butyl, isobutyl, sec-butyl, t-butyl, n-penty 4, isopentyl, neopentyl, tert-amyl, and hexyl, and longer alkyl groups, such as heptyl, octyl, and the like.

[0050] 25 Non-limiting examples of straight alkyd groups include methyl, ethyl, propyl, butyl, pentyd, hexyl, heptyl, octyl, nonyl, and decyl.

[0051] Branched alkyl groups include any straight alkyl group substituted with any number of alkyl groups. Non-limiting examples of branched alkyd groups include isopropyl, isobutyl, sec-butyl, and t- butyd.

[0052] 30 Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalky !, heteroaryl, and the like. In some embodiments, the alkyd is optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyd is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkyl is optionally

[0053] 5 substituted with halogen. Non-limiting examples of substituted alkyd groups includes hydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl, 1 -chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, and 3- carboxy propyl.

[0054] “Alkenyl” refers to an optionally substituted straight-chain, or optionally substituted branched-

[0055] 5 chain hydrocarbon having one or more carbon-carbon double-bonds. The olefin or olefins of an alkenyl group can be, for example, E, Z, cis, trans, terminal, or exo-methylene. An alkenyl group can be, for example, a group that is substituted or unsubstituted. Non-limiting examples of alkenyl and 10

[0056] 10 alkenylene groups include ethenyl, prop-l-en-l-yl, isopropenyl, but-1-en-4-yk 2-chloroethenyl, 4- hydroxybuten- 1 -yl, 7 -hy droxy-7-methyloct-4-en-2-yl, and 7-hydroxy-7 -methyloct-3,5-dien-2-yl.

[0057] Whenever it appeal's herein, a numerical range such as “C2-C6 alkenyl” means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no

[0058] 15 numerical range is designated. In some embodiments, the alkenyl is a C2-C10 alkenyl, a C2-C9 alkenyl, a C2- C8 alkenyl, a C2-C7 alkenyl, a C2-C6 alkenyl, a C2-C5 alkenyl, a C2-C4 alkenyl, a C2-C3 alkenyl, or a C2 alkenyl. Unless slated otherwise specifically in the specification, an alkenyl group is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an alkenyl is optionally

[0059] 20 substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NHz, or -NO2. In some embodiments, an alkenyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkenyl is optionally substituted with halogen.

[0060] “Alkynyl” refers to an optionally substituted straight-chain or optionally substituted branch ed- chain hydrocarbon. The triple bond of an alkynyl group can be internal or terminal. An alkynyl or

[0061] 25 alky nylene group can be, for example, a group that is substituted or unsubstituted. Non- limiting examples of alkynyl groups include ethynyl, prop-2-yn-l-yl, prop-l-yn-l-yl, and 2-methyl-hex- 4-yn-l-yl; 5-hydroxy-5-methylhex-3-yn-l-yl, 6-hydroxy-6-methylhept-3-yn-2-yl, and 5-hydroxy-5-

[0062] 30 ethylhept-3-yn-I -yl.

[0063] Whenever it appears herein, a numerical range such as “C2-C6 alkynyl” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated. In some embodiments, the alkynyl is a C2-C10 alkynyl, a C2-C9 alkynyl, a

[0064] 6 C2-C8 alkynyl, a C2-C7 alkynyl, a C2-C6 alkynyl, a C2-C5 alkynyl, a C2-C4 alkynyl, a C2-C3 alkynyl, or a C2 alkynyl. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an alkynyl is optionally

[0065] 5 substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, an alkynyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkynyl is optionally substituted with halogen.

[0066] A haloalkyl group can be any alkyl group substituted with any number of halogen atoms, for example, fluorine, chlorine, bromine, and iodine atoms. A halo-alkenyl group can be any alkenyl group

[0067] 10 substituted with any number of halogen atoms. A haloalkynyl group can be any alkynyl group substituted with any number of halogen atoms.

[0068] An alkoxy group can be, for example, an oxygen atom substituted with any alkyd, alkenyl, or alkynyl group. An ether or an ether group comprises an alkoxy group. Non-limiting examples of alkoxygroups include methoxy, ethoxy, propoxy, isopropoxy, and isobutoxy.

[0069] 15 The term "acyl" refers to the groups HC(O)-, alkyl-C(O)-, cycloalkyl-C(O)-, cycloalkenyl-C(O)-, aryl-C(O)-, heteroaryl-C(O)- and heterocyclyl-C(O)- where alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl are as described herein. By way of example acyl groups include acetyl and benzoyl groups.

[0070] “Alkoxy” refers to a radical of the formula -ORawhere Rais an alkyl radical as defined. Unless

[0071] 20 stated otherwise specifically in the specification, an alkoxy group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an alkoxy is optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, an alkoxy is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkoxy is

[0072] 25 optionally substituted with halogen. ‘Aminoalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines Hydroxyalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the hydroxyalky is

[0073] 30 aminomethyl.

[0074] “Aryl” refers to a radical derived from a hydrocarbon ring system comprising hydrogen, 6 to 30 carbon atoms, and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricy clic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocyclylalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the

[0075] 7 aryl is a 6- to 10-membered and. In some embodiments, the aryl is a 6-membered aryl. Aryl radicals include, but are not limited to, aryd radicals derived from the hydrocarbon ring systems of anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as- indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and

[0076] 5 triphenylene. In some embodiments, the aryl is phenyl. Unless stated otherwise specifically in the specification, an and may be optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an aryd is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, an and is optionally substituted with halogen,

[0077] 10 methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryd is optionally substituted with halogen.

[0078] "‘Cycloalkyl” refers to a stable, partially or fully saturated, monocy clic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryd ring, the cycloalkyl is bonded through anon-aromatic ring atom), bridged, or spiro ring systems. Representative cycloalkyls include,

[0079] 15 but are not limited to, cycloalkyls having from three to fifteen carbon atoms (C3-C15 cycloalkyl), from three to ten carbon atoms (C3-C10 cycloalkyd), from three to eight carbon atoms (Cs-Cs cy cloalkyd), from three to six carbon atoms (C3-C6 cycloalkyl), from three to five carbon atoms (C3-C5 cycloalkyl), or three to four carbon atoms (C3-C4 cycloalkyl). In some embodiments, the cycloalkyl is a 3- to 6-membered cy cloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl. Non-limiting

[0080] 20 examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups. Cycloalkyl groups also include fused-, bridged-, and spiro-bicycles and higher fused-, bridged-, and spiro-sy stems. A cycloalkyl group can be substituted with any number of straight, branched, or cyclic alkyl groups. Non-limiting examples of cyclic alkyl groups include cyclopropyl, 2- methyd-cycloprop-1 -yd, cycloprop-2-en-l-yd, cyclobutyl, 2,3-dihydroxycyclobut-l-yl, cyclobut-2-en-1 -yl,

[0081] 25 cyclopentyl, cyclopent-2-en-l-yl, cyclopenta-2,4-dien-l-yd, cyclohexyl, cyclohex-2-en-l-yl, cycloheptyd, cyclooctanyl, 2,5-dimethylcyclopent-l-yl, 3,5-dichlorocyclohex-l-yl, 4-hydroxycyclohex-l-yl, 3,3,5- trimethylcyclohex-l-yl, octahydropentalenyl, octahydro- IH-indenyl, 3a,4, 5,6,7, 7a-hexahydro-3AT-inden- 4-yl, decahydroazulenyl, bicyclo-[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3. 1.1 Jheptanyl, 1,3- dimethyl[2.2.1]heptan-2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl.

[0082] 30 Monocy clic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0083] Polycyclic cycloalkyds or carbocycles include, for example, adamantyl, norbomyl, decalinyL bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane,

[0084] 8 bicyclo[2.2. 1 |heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bi cyclo [3.3.2] decane, and 7,7-dimethyl-bicyclo|2.2.1 Jheptanyl.

[0085] Partially saturated cycloalkyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless stated otherwise specifically in the specification, a cycloalkyl is optionally

[0086] 5 substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyd, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF?,, -OH, -OMe, -NH2, or - NO2. In some embodiments, a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl is optionally substituted with halogen.

[0087] 10 “Deuteroalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more deuteriums. In some embodiments, the alkyl is substituted with one deuterium. In some embodiments, the alkyl is substituted with one, two, or three deuteriums. In some embodiments, the alkyl is substituted with one, two, three, four, live, or six deuteriums. Deuteroalkyl include, for example, CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. In some embodiments, the deuteroalkyl

[0088] 15 is CD3.

[0089] “Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halogens. In some embodiments, the alkyl is substituted with one, two, or three halogens. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six halogens. Haloalkyl include, for example, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2, 2,2 -trifluoroethyl,

[0090] 20 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like. In some embodiments, the haloalkyl is trifluoromethyl.

[0091] “Halo” or “halogen” refers to bromo, chloro, fluoro, or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro.

[0092] “Heteroalkyl” refers to an alkyd group in which one or more skeletal atoms of the alkyl are

[0093] 25 selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g.,

[0094] -NH-, -N(alkyl)-), sulfur, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C1-6 heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen (e.g. -NH-, -N(alkyl)-), sulfur, or combinations thereof wherein the heteroalkyl is attached to the

[0095] 30 rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl are, for example, - CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, or -CH(CH3)OCH3. Unless stated otherwise specifically in the specification, a heteroalkyl is optionally substituted for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, and, cycloalkyd, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heteroalkyl is optionally substituted

[0096] 9 with oxo, halogen, methyl, ethyl, -CN, -CF3 -OH, -OMe, -NH2, or -NO2. In some embodiments, a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroalkyl is optionally substituted with halogen.

[0097] "‘Hydroxyalkyd'’ refers to an alkyl radical, as defined above, that is substituted by one or more

[0098] 5 hydroxy ls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl include, for example, hydroxymethyl , hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyd is hydroxymethyl.

[0099] A heterocycle can be any ring containing a ring atom that is not carbon, for example, N, O, S, P,

[0100] 10 Si, B, or any other heteroatom. A heterocycle can be substituted with any number of substituents, for example, alkyd groups and halogen atoms. A heterocycle can be aromatic (heteroaryl) or non-aromatic. Non-limiting examples of heterocycles include pyrrole, pyrrolidine, pyridine, pyrimidine, pyrazine, pyridazine, piperidine, succinimide, maleimide, morpholine, imidazole, thiophene, furan, tetrahydrofuran, pyran, and tetrahydropyran.

[0101] 15 “Heterocyclyl” refers to a stable 3- to 24-membered heterocycle. Non-limiting examples of heterocycles include: heterocyclic units having a single ring containing one or more heteroatoms, non- limiting examples of which include, diazirinyl, aziridinyl, azetidinyl, pyrazolidinyl, imidazolidiny 1, oxazolidinyl, isoxazolinyl, thiazolidinyl, isothiazolinyl, oxathiazolidinonyl, oxazolidinonyl, hydantoinyl, tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperazinyl, piperidinyl, dihydropyranyl, tetrahydropyranyl,

[0102] 20 piperidin-2-onyl, 2,3,4,5-tetrahydro-1H -azepinyl, 2, 3-dihydro1H -indole, and 1 ,2,3,4- tetrahydroquinoline; and ii) heterocyclic units having 2 or more rings one of which is a heterocyclic ring, non-limiting examples of which include hexahydro- 1 / Z-pyrrolizinyl, 3a,4,5,6,7,7a-hexahydro-1H - benzo[d]imidazolyl, 3a,4,5,6,7.7a-hexahydro-1H -indolyl, 1 ,2,3,4-tetrahydroquinolinyL and decahydro- 17Z-cycloocta[b]pyrrolyl.

[0103] 25 “Heterocyclylalkyl” refers to a stable 3- to 24-membered partially or fully saturated ring radical comprising 2 to 23 carbon atoms and from one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur. Unless stated otherwise specifically in the specification, the heterocyclyl alkyl radical may be a monocy clic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocyclylalkyl is bonded through a

[0104] 30 non-aromatic ring atom) or bridged ring systems; and die nitrogen, carbon, or sulfur atoms in the heterocyclylalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quatemized.

[0105] Representative heterocyclylalkyls include, but are not limited to, heterocyclylalkyls having from two to fifteen carbon atoms (C2-C15 heterocyclylalkyl), from two to ten carbon atoms (C2-C10 heterocyclylalkyl), from two to eight carbon atoms (C2-C8 heterocyclylalkyl), from two to six carbon

[0106] 10 atoms (Cs-C6 heterocyclylalkyl), from two to five carbon atoms (C2-C5 heterocyclylalkyl), or two to four carbon atoms (C2-C4 heterocyclylalkyl). In some embodiments, the heterocyclylalkyl is a 3- to 6- membered heterocy clylalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered heterocyclylalkyl. Examples of such heterocyclylalkyl radicals include, but are not limited to, aziridinyl,

[0107] 5 azetidinyl, dioxolanyl, thienyl[l,3]dithianyL decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl , octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofury 1, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyL 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-l-yl, 3-

[0108] 10 oxo-1, 3-dihydroisobenzofuran-l-yl, methyl -2-oxo-l,3-dioxol-4-yl, and 2-oxo-l,3-dioxol-4-yl. The term heterocyclylalkyl also includes all ring forms of the carbohydrates, including but not limited to, the monosaccharides, the disaccharides, and the oligosaccharides. It is understood that when referring to the number of carbon atoms in a heterocyclylalkyl, the number of carbon atoms in the heterocyclylalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocyclylalkyl

[0109] 15 (i.e. skeletal atoms of the heterocyclylalkyl ring). Unless stated otherwise specifically in the specification, a heterocyclylalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heterocyclylalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a heterocyclylalkyl is

[0110] 20 optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocyclylalkyl is optionally substituted with halogen.

[0111] “Heteroaryf’ refers to a 5- to 14-membered ring system radical comprising hydrogen atoms, one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur, and at least one aromatic ring, he heteroaryl radical may be a monocyclic,

[0112] 25 bicyclic, tricyclic, or tetracyclic ring system, wInch may include fused (when fused with a cycloalkyl or heterocyclylalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems, and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quatemized. In some embodiments, the heteroaryl is a 5- to 10- membered heteroaiyl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. Examples

[0113] 30 include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][l,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl,

[0114] 11 furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl. indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1- oxidopyridinyl, 1 -oxidopyrimidinyl, 1 -oxidopyrazinyl, 1-oxidopyridazinyl, 1 -phenyl -IH-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl,

[0115] 5 pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless stated otherwise specifically in the specification, a heteroaryl is optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heteroary l is optionally

[0116] 10 substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroaryl is optionally substituted with halogen.

[0117] II Compounds

[0118] 15 In one embodiment enhancers of pesticidal activity disclosed herein include those having the Formulas set forth below. In one embodiment, the present disclosure provides a method for inhibiting apyrase, comprising contacting the apyrase with a compound of Formula (I) (I), wherein

[0119] R1and R2are independently selected from C1-6 alkyl optionally substituted with one or more R5,

[0120] 20 C6-10 aryl, optionally substituted with one or more R5, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more R5, C5-10 heteroaryl optionally substituted with one or more R5and heterocy clylalkyl optionally substituted with one or more R5;

[0121] R3and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl, C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they

[0122] 25 are attached form a dihydrophthalazine- 1,4-dione; or each R5is independently selected from Ra, Rb, Rasubstituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)m-Rb, -(CHRa)m-Rb,

[0123] 12 each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10 and, C5-10 heteroaryl, C6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;

[0124] 5 Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -ORa, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are attached, forms a. 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and R8substituted with one or more Rb, Rd, or both;

[0125] Rbis independently selected from the group consisting of =0, -ORdhalogen, C1.3 haloalkyloxy,

[0126] 10 -OCF3, ==S, -SRd, ==NRd, =N0Rd, -NR°R°, -SF5, halogen, -CF3, -CN, -NO2, -S(O)Rd-S(O)2Rd, -S(O)2ORd, -S(O)NR°R°, -S(O)2NR°R°, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NR“R°, -C(O)Rd, -C(O)ORd, -C(O)NR°RC, -C(NH)NRCR‘, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NR°RC, -OC(O)Rd, -OC(O)ORd, -OC(O)NR°R°, -OC(NH)NRCR°, -OC(NRa)NR“R°, -[NHC(O)J„Rd, -[NRaC(O)]„Rd, -[NHC(O)J„ORd,

[0127] 15 -[NRaC(O)]„ORd, -[NHC(O)]„NRCR°, -[NRaC(O)]„NRcRc, -[NHC(NH)]„NR°R° and -[NRaC(NRa)]„NR°Rc; each R° is independently Ra, or, alternatively, two R° are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be

[0128] 20 substituted with one or more of the same or different Regroups; each Rdis independently hydrogen or C 1-6 alkyl; each R6is independently halogen, C1-6 alkyl or -C(O)Rd; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

[0129] 25 In one embodiment, enhancer compounds of Formula (I) have Formula (la) (la), R1and R2are independently selected from C1-6 alkyl optionally substituted with one or more Raoptionally substituted with one or more Ra, Rb, or both; C6-10 aryl, optionally substituted with one or more R3, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more R3, C 5-10 heteroaryl optionally substituted with one or more R5and heterocyclylalkyl

[0130] 30 optionally substituted with one or more R5;

[0131] 13 R3and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl Cs-ioheteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they are attached form a dihydrophthalazine- 1,4-dione; or each R5is independently selected from Ra, Rb, Rasubstituted with one or more R“, Rb, or both and

[0132] 5 -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)m-Rb, -(CHRak-Rb, -O-(CH2)m-Rb, -S-(CH2)„,-Rb, -O-CHRaRb. -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb, -O-(CH2)m-C(O)NH-(CH2)m-Rb;

[0133] 10 each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-e alkenyl, C2-6alkynyl, C1-6 haloalkyl C3-8 cycloalkyl C6-10 aryl, C 5-10 heteroaryl, C6-16 arylalkyl 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;

[0134] Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -ORa, C1-6

[0135] 15 haloalkyl, or Z, together with R4and the atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;

[0136] Rbis independently selected from the group consisting of =0, -ORd, halogen, C1-3 haloalkyloxy, -OCF3, =S, -SRd, =NRd=N0Rd, -NR°RC, -SF5, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)2Rd

[0137] 20 -S(O)2ORd, -S(O)NR°R°, -S(O)2NRCRC, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NR°R°, -C(O)Rd-C(O)ORd, -C(O)NR°R°, -C(NH)NRCR°, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRaR°, -OC(O)Rd, -OC(O)ORd, -OC(O)NRCRC, -0C(NH)NR°R°, -OC(NRa)NRcR°, -[NHC(0)]„Rd, -|NRaC(0)]„Rd, -[MIC(0)]„0Rd-[NRaC(O)]«ORd-[NHC(0)]nNR°Rc, -[NRaC(O)]„NR°R°, -[NHC(NH)]„NR°R° and

[0138] 25 -[NRaC(NRa)]„NRcRc; each Rcis independently Ra, or, alternatively, two R“ are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which max’ optionally be substituted with one or more of the same or different Regroups;

[0139] 30 each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(O)Rd; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

[0140] In one embodiment of compounds having Formula (I), disclosed enhancers have Formula (lb)

[0141] 14 wherein R1, R2, R3, R4and Z are as described with respect to Formula (I).

[0142] In one embodiment of compounds having Formula (I), disclosed enhancers have Formula (Ic) (Ic) wherein R1, R2, R3, R4and Z are as described with respect to Formula (I).

[0143] In certain embodiments of compounds according to Formulas (I), (la), (lb) and (Ic) at least one of

[0144] 5 R1and R2is ary l, such as wherein R1is aryl, R2is aryl, or both R1and R2are aryl. In embodiments of compounds according to Formulas (I), (la), (lb) and (Ic), R1is aryl, wherein R2is selected from C1-6 alkyl, aryl and heteroaryl. In embodiments of compounds according to Formulas (I), (la), (lb) and (Ic), R2is aryl, wherein R1is selected from C1-6 alkyd optionally substituted with one or more Raand Rb, aryl optionally substituted with one or more R\ aralkyl optionally substituted with one or more R3,

[0145] 10 heterocyclyl optionally substituted with one or more Rdand heteroaryl optionally substituted with one or more R\ In certain embodiments of compounds according to Formulas (1), (la), (lb) and (Ic), wherein R1, R2, or both are aryl, the aryl is substituted or unsubstituted. In certain embodiments of compounds according to Formulas (I), (la), (lb) and (Ic), wherein R1, R2, or both are aryl, at least one aryl is substituted or unsubstituted phenyl.

[0146] 15 In one embodiment of compounds according to Formulas (I), (la), (lb) and (Ic) at least one of R1and R2is aryl or heteroaryl. In one embodiment of compounds according to Formulas (I), (la), (lb) and (Ic) at one of R1and R2is aryl and the other of R1and R2is heteroaryl. In one embodiment wherein Ar1and Ar2are independently selected from aryl and heteroaryl each is optionally substituted with one or more R '.

[0147] 20 In one embodiment of compounds according to Formulas (I), (la), (lb) and (Ic) at least one of R1and R2is heteroaryl, such as wherein R1is heteroaryl, R2is heteroaryl, or both R1and R2are heteroaryl. In certain embodiments of compounds according to Formulas (I), (la), (lb) and (Ic), wherein R1, R2, or both are heteroaryl, the heteroaryl is substituted or unsubstituted with one or more R3.

[0148] In one embodiment of compounds according to Formulas (I), (la), (lb) and (Ic) at least one of R1

[0149] 25 and R2is substituted with one or more Rj. In one such embodiment, of compounds according to Formulas (I), (la), (lb) and (Ic) at least one of R1and R2is substituted with one or more R3.

[0150] In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), at least one of R1and R2is substituted with one or more R5and each R5is independently selected from is independently selected from Ra, Rb, Rssubstituted with one or more Ra,

[0151] 15 Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)OT-Rb, -(CHRa)„,-Rb, -O-(CH2)m-Rb, -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)„,-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb, -O-(CH2),n-C(O)NH-(CH2)m-Rb.

[0152] 5 In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), at least one of R1and R2is substituted with one or more R5wherein at least one R3is halogen.

[0153] In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), at least one of R1and R2is substituted with one or more R5wherein at least one R5

[0154] 10 is -ORasubstituted with one or more of the same or different Raor Rb.

[0155] In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), R1and R2are the same. In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), at least one of R1and R2is C1-6 alkyl. In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la),

[0156] 15 (lb) and (Ic), one of R1and R2is aralkyl optionally substituted with one or more R5. In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), one of R1and R2is cycloalkyl optionally substituted with one or more R5. In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), one of R1and R2is heteroaryl optionally substituted with one or more R5. In one embodiment of compounds disclosed

[0157] 20 herein, including compounds according to Formulas (I), (la), (lb) and (Ic), one of R1and R2is heterocyclyl alkyl optionally substituted with one or more R5.

[0158] In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), at least one of R3and R4is hydrogen. In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), at least one of RJand R4is

[0159] 25 C1-6 alkyd.

[0160] In one embodiment of compo unds disclosed herein according to Formula (I), the compound has Formula (II)

[0161] In one embodiment of compounds discl osed herein according to Formula (I), R3is Rathat

[0162] 30 together with R1and the nitrogen they' are both attached to thereto forms a heterocyclylalkyl optionally substituted with one or more R“. In one embodiment of compounds disclosed herein according to

[0163] 16 Formula (I), R4is Rathat together with R2and the nitrogen they are both attached to thereto forms a heterocyclylalkyl optionally substituted with one or more Rd.

[0164] In one embodiment of compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), R1and R2independently are selected from

[0165] F H HN

[0166] 17

[0167] In one embodiment of enhancer compounds disclosed herein, including compounds according to Formulas (I), (la), (lb) and (Ic), the compound is selected from:

[0168] N1,N4-di-p-toly Iterephthal amide;

[0169] N1,N4-bis(3-(methy Ithi o)pheny I )terephthalami de;

[0170] N1,N4-diphenylterephthalamide;

[0171] N^t^-chlorobenzotdltl ^Jdioxol-S-yO-N3-phenylisophthalamide;

[0172] Nl,N4-bis(benzo[d][l,3]dioxol-5-yl)terephthalamide;

[0173] N1,N4-bis(2,3-dihy drobenzo[b] [ 1 ,4]dioxin-6-yl)terephthal amide; diethyl 4,4'-(isophthaloylbis(azanediyl))dibenzoate;

[0174] N1-cyclohexyl-N2-(2-methoxy-5-methylphenyl)-N1-methylphthalamide;

[0175] N1-(3-(lH-l,2,3-triazol-l-yl)phenyl)-N4-(3-methylbenz)'l)terephthalamide; l,3-dioxo-N-(3-(pyrrolidin-l-yl)phenyl)isoindoline-5-carboxamide;

[0176] N1-(3-(4,4-dimethyi-2,5-dioxoimidazolidin-l-yl)phenyl)-N'1-phenylisophthalamide;

[0177] Nl-(3 ,4-dihy dro-2H-benzo[b] [ 1 ,4] dioxepin-7 -yl)-N2,N2-di methy Iphthalami de;

[0178] N1-(4-(ethylcarbamoyl)quinolin-2-yl)-N4-phenyIterephthalamide;

[0179] N1,N2-bis(2-chlorophenyl)phthalimide;

[0180] 2-isobutyl-3-methyl-2,3-dihydrophthalazine-l, 4-dione;

[0181] Nl-(4-(benzo[d][l,3]dioxol-5-yl)-lH-pyrazol-5-yl)-N3-phenylisophthalamide;

[0182] NI,N'-bis(4-(lH-imidazol-4-yl)phenyl)isophthalamide;

[0183] N'-(benzo[d|[l,3|dioxol-5-yl)-N2-cyclohexyl-N2-methylphthalamide;

[0184] Nl,Ns-bis(3-metby I- 1 H-indazol -6-yl)i sophthal ami de;

[0185] Nl,N4-bis(3,5-dimethoxyphenyl)terephthal amide;

[0186] 2-((3-ethyl-5-methylisoxazol-4-yl)methyl)-3-methyl-2,3-dihydrophthalazine-l, 4-dione;

[0187] N1-(2-ethyl-2H-indazol-6-yl)-N3-methylisophthal amide.

[0188] 18 N 1 -phenyl-N4-(3-phenylprop-2-yn-1 -yl)terephthalamide;

[0189] N-(2-isopropyl-2H-indazol-6-yl)-l,3-dioxoisoindoline-5-carboxamide;

[0190] 2-(4-amino-2-chlorophenyl)isoindoline-l, 3-dione;

[0191] 2-((5-cbloro-l-methyl-lH-pyrazol-3-yl)methyl)-3-methyl-2,3-dihydrophthalazine-i, 4-dione;

[0192] N1-(3-( IH-imidazoi- 1 -yl)benzyl)-N4-phenylterephthal amide;

[0193] N1-(2-methoxy-2-methylpropyl)-N4-phenylterephth al amide;

[0194] N1-(3 -( 1 H-tetrazol -5 -yl)phenyl)-N3-phenyli sophthal ami de;

[0195] N* ,N2-dibenzylphthalamide;

[0196] 2-(4-methoxybut-2-yn-l-yl)-3-methyl-2,3-dihydrophthalazine-l, 4-dione;

[0197] N1-(l-(l,l-dioxidothiomorpholino)-l-oxopropan-2-yl)-N3-phenylisophthal amide;

[0198] N-(3-nitrophenyl)-2-(pyrrolidine-l-carbonyl)benzamide;

[0199] N1-(5,6-dihydro-4H-pyrrolo[l,2-b]pyrazol-2-yl)-N4-phenylterephthalamide;

[0200] N1-(4-cy ano-3 -(trifl uoromethyl)pheny 1)-N3-methylisophthal amide,

[0201] N1, N3-bis(2-oxo-2, 3,4, 5-tetrahydro- lH-benzo[b]az.epin-7-yl)isophth al amide;

[0202] N1-benzyl-N2-(2,6-dimethylphenyl)-Nl -methylphthal amide;

[0203] N^5-methyl-lH-imidazol-2-yl)-N4-phenylterephthalamide;

[0204] N^S-methyl-lH-l^^-triazol-S-yty-N^phenylterephthalamide;

[0205] Nl-benzyl-N2-(2-methoxyphenyl)-N 1 -methylphthalamide;

[0206] N1-(benzo[d]thiazol-5-yl)-N4-cyclopropylterephthal amide;

[0207] Nl-phenyl-N4-((lJ?,25)-2-phenylcjclopropyl)terephthalamide;

[0208] N^cyclohexyl-N^Tnethyl-N^fS-CtrifluorornethyOphenyOphthalimide;

[0209] N1-(3-(cy'clopentylamino)phenyl)-N3-methylisophthalamide;

[0210] N1,N4-bis(2,4-dimethoxyphenyl)terephthalamide;

[0211] N1,N4-bis(4-(2-oxopyrrolidin-1 -yl)phenyl)terephthalamide;

[0212] Nl-(2-(lH-imidazol-2-yl)phenyl)-N4-cyclopropylterephthalamide;

[0213] N1-((lH-imidazol-2-yl)methyl)-N4-phenylterephthalamide;

[0214] Nl-(2-(3-methyl-4H-l,2,4-triazol-4-yl)ethyl)-N4-phenylterephthalamide;

[0215] N1-methyl-N3-(2-oxo-2,3-dihydrobenz.o[d]thiazol-6-yl)i sophthal amide;

[0216] N1,N4-dimesi ty 1 terephthalamide;

[0217] N’-(2H-indazol-6-yl)-N3-propylisophthalamide;

[0218] N-(4-fluorophenyl)-2-(4-methylpiperazine-l-carbonyl)benzamide;

[0219] N1,N3-bis( 1 -oxoi soindol in-4-y 1 )i soph thalamide;

[0220] Nl-((4-aminopyrimidin-2-yl)methyl)-N4-phenylterephthal amide;

[0221] Nl-methyl-N3-(4-((trifluoromethyl)sulfonamido)phmyl)isophthal amide;

[0222] 19 N1-(lH-indazol-7-yl)-N3-propylisophthalamide;

[0223] N-(3 -ethy ny Iphenyl)-2-(4-methylpiperazine- 1 -carbonyl)benzamide;

[0224] 2-((5-cyclopropyl-l, 3, 4-oxadiazol-2-yl)methyl)-3-methyl-2,3-dihydrophthaIazine-l, 4-dione;

[0225] 5-oxo-N-(2-oxo-2, 3,4, 5-telrahydro-lH-benzo[b]azepin-8-yl)-2, 3,4,5- tetrahydrobenzo[f] [ 1 ,4]oxazepine-7 -carboxamide; and

[0226] N1-phenyl-N4-( 1 -((tetrahydrofuran-2-yl)methyl)-l H-pyrazol-4-yl)terephthalamide.

[0227] Specific examples of apyrase inhibitors according to the present disclosure, including compounds of Formulas (I), (la), (lb), (Ic) and / or (II), for use to enhance the activity of an agricultural or horticultural pesticide as described herein, are illustrated below in Table I :

[0228] 5

[0229]

[0230]

[0231] III. Target Crops and their Pathogens

[0232] The present disclosure provides formulations and methods for their use in treating crops for

[0233] 5 pathogens. In one embodiment, a. disclosed compound, such as a compound of Formulas (I), (la), (lb), (Ic) and / or (II), is administered in combination with an agricultural or horticultural pesticide, such as an acaricide, antimicrobial, fungicide, herbicide, insecticide, molluscicide and / or nematocide. Crops that can be treated, include those plagued by various pathogens, including without limitation, bacteria, viruses, fungal pathogens, mites, nematodes, molluscs, weeds or other pests, as is known to those of

[0234] 10 ordinary7skill in the agricultural arts. By way of example, such agricultural and horticultural crops that can be treated according to the present disclosure include plants, whether genetically modified or not, including their harvested products, such as: cereals; vegetables; root crops; potatoes, trees such as fruit trees, for example banana trees, tea coffee trees, or cocoa trees; grasses; lawn grass: or cotton.

[0235] Roux and coworkers describe the compound:

[0236] 15 , referred to herein as “Roux compound 13 / ’ as enhancing the ability of certain fungicides to inhibit the growth of different plant-pathogenic fungi {Molecular Plant Pathology, 2017, 18(7), 1012 - 1023; and WO 2016 / 123191). The present compounds surprisingly enhance the ability of a variety of pesticides against a broad variety of pathogens, including fungal pathogens. In addition, examples of the presently disclosed compound exhibit superior enhancer activity 29 than Roux compound 13.

[0237] The agricultural or horticultural enhancer disclosed herein may be applied to each part of plants, such as leaves, stems, patterns, flowers, buds, fruits, seeds, sprouts, roots, tubers, tuberous roots, shoots, or cuttings. The agricultural or horticultural enhancer according to the present disclosure may also be

[0238] 5 applied to improved varieties / varieties, cultivars, as well as mutants, hybrids and genetically modified embodiments of these plants.

[0239] The agricultural or horticultural treatment described herein may be used to conduct seed treatment, foliage application, soil application, or water application, so as to control various diseases occurring in agricultural or horticultural crops, including flowers, lawns, and pastures.

[0240] 10 The present compounds are useful for potentiating the effects of antimicrobial agents. For example, the present compounds can be used in combination with an antimicrobial agent to combat bacterial and viral infection.

[0241] The present compounds are useful for potentiating the effects of herbi cides. For example, tlie present compounds can be used in combination with one or more herbicide to control weeds or other

[0242] 15 unwanted vegetation.

[0243] The present compounds are useful for potentiating the effects of insecticides. For example, the present compounds can be used in combination with one or more insecticide to control insect infestation. The present compounds are usefill for potentiating tire effects of acaricides or miticides. For example, the present compounds can be used in combination with one or more acaricidal agent to control mites.

[0244] 20 The present compounds are useful for poten tiating tlie effects of molluscicides. For exampl e, the present compounds can be used in combination with one or more molluscicide to prevent interference of slugs or snails with a crop.

[0245] The present compounds are useful for potentiating the effects of nematocides. For example, the present compounds can be used in combination with one or more nematocide to prevent interference of

[0246] 25 nematodes with a crop.

[0247] The present compounds are particularly useful for potentiating the effects of fungicides against plant fungal pathogens. Examples of pathogens treated according to the present disclosure include, without limitation, Botrytis cinerea, Colletotrichwn graminicola, Fusarium oxysporum, Sclerotiana sclerotiorum, Verticillium dahlia, Mycospharella gramincola and Sphacelotheca reliana.

[0248] 30 Botrytis cinerea is an airborne plant pathogen with a necrotrophic lifestyle attacking over 200 crop hosts worldwide. It mainly attacks dicotyledonous plant species, including important protein, oil, fiber and horticultural crops, grapes and strawberries and also Botrytis also causes secondary soft rot of fruits and vegetables during storage, transit and at the market. Many classes of fungicides have failed to control Botrytis cinerea due to its genetic plasticity.

[0249] 30 The genus Collet otrichum comprises -600 species attacking over 3,200 species of monocot and dicot plants. Colletotrichum graminicola primarily infects maize (Zea mays), causing annual losses of approximately 1 billion dollars in the United States alone (Connell et al., 2012).

[0250] Fusarium wilt of banana, caused by the soil-bome fungus P'usarium oxysporum f.sp. cubense, is a

[0251] 5 major threat to banana production worldwide. No fungicides are currently available to effectively control the disease once plants are infected (Peng J et al., 2014).

[0252] Tire white mold fungus Sclerotinia sclerotiorum is known to attack more than 400 host species and is considered one of tire most prolific plant pathogens. The majority of the affected crop species are dicotyledonous, along with a number of agriculturally significant monocotyledonous plants. Some

[0253] 10 important crops affected by S. sclerotiorum include legumes (soybean), most vegetables, stone fruits and tobacco.

[0254] The ascomycete Verticillium dahlias is a soil-home fungal plant pathogen that causes vascular wilt diseases in a broad range of dicotyledonous host species. V. dahliae can cause severe yield and quality losses in cotton and other important crops such as vegetables, fibers, fruit, nut trees, forest trees

[0255] 15 and ornamental plants.

[0256] The ascomycete fungus Mycospharella gramincola (anamorph: Septoria tritici) is one of the most important foliar diseases of wheat leaves, occurring wherever wheat is grown. Yield losses attributed to this disease range from 25%-50%, and are especially high in Europe, the Mediterranean region and East .Africa. Infection by M. gramincola is initiated by air borne ascopores produced on residues of last

[0257] 20 season's crop. Primary' infection usually occurs after seedlings emerge in spring or fall. The mature disease is characterized by necrotic lesions on the leaves and stems of infected plants.

[0258] The basidiomycete fungus Sphacelotheca reliana infects com (Zea mays) systemically, causing Head Smut. Yield loss attributed to the disease is variable, and is directly dependent on the incidence of the disease. The fungus overwinters as diploid teliospores in crop debris or soil. Floral structures are

[0259] 25 converted to sori containing masses of powdery teliospores that resemble mature galls of common smut.

[0260] Examples of crops to be treated and plant diseases (pathogens) to be controlled using the presently disclosed compounds and compositions include, without limitation:

[0261] Sugar beet: brown spot disease (Cercospora beticold), black root disease (Aphanomyces cochlioides), root rot disease (Thanatephorus cucumeris), leaf' rot disease (Thanatephorus cucumeris),

[0262] 30 and the like.

[0263] Peanut: brown spot disease (Mycosphaerella arachidis), leaf mold (Ascochyta sp.), rust di sease (Puccinia arachidis), damping-off disease (Pythium debaryanum), rust spot disease (Alternaria alternata), stem rot disease (Sclerotium rolfsii), black rust disease (Mycosphaerella berkeleyi), and the like.

[0264] 31 Cucumber: powdery mildew (Sphaerotheca fuliginea), downy mildew (Pseudoper onospora cubensis), gummy stem blight (Mycosphaerella melonis), wilt disease (Fusarium oxysporum), sclerotinia rot (Sclerotinia sclerotiorum), gray mold (Botrytis cinered), anthracnose (Colletotrichum orbiculare), scab (Cladosporium cucumerinum), brown spot disease (Corynespora cassiicola), damping-off disease

[0265] 5 (Pythium debaryanum, Rhizoctonia solant Kuhn), Phomopsis root rot disease (Phomopsis sp.), Bacterial spot (Pseudomonas syringae pv. Lechrymans), and the like.

[0266] Tomato: gray7mold disease (Botrytis cinered), leaf mold disease (Cladosporium fulvum), late blight disease (Phytophthora infestans), Verticillium wilt disease (Verticillium albo-atrum, Verticillium dahliae), powdery mildew disease (Oidium neolycopersici), early blight disease (Alternaria solani), leaf

[0267] 10 mold disease (Pseudocercospora fiiligend), and the like.

[0268] Eggplant: gray mold disease (Botrytis cinered), black rot disease (Corynespora melongenae), powdery mildew disease (Erysiphe cichoracearum), leaf mold disease (Mycovellosiella nattrassii), sclerotinia rot disease (Sclerotinia sclerotiorum), Verticillium wilt disease (Verticillium dahlia), Mycosphaerella blight (Phomopsis vexans), and the like.

[0269] 15 Strawberry: gray mold disease (Botrytis cinerea), powdery mildew disease (Sphaerotheca humuli), anthracnose disease (Colletotrichum acutatum, Colletotrichum fragariae), phytophthora rot disease (Phytophthora cactorum), soft rot disease (Rhizopus stolonifer), fusarium wilt disease (Fusarium oxysporum), verticillium wilt disease (Verticillium dahlia), and the like.

[0270] Onion: neck rot disease (Botrytis allii), gray mold disease (Botrytis cinerea), leaf blight disease

[0271] 20 (Botrytis squamosa), downy mildew' disease (Peronospora destructor), Phytophthora pom disease (Phytophthora porn}, and the like.

[0272] Cabbage: clubroot disease (Plasmodiophora brassicae), soft rot disease (Erwinia carotovora), black rot disease (Xanthomonas campesrtis pv. campestris), bacterial black spot disease (Pseudomonas syringae pv. Maculicola, P.s. pv. alisalensis), downy mildew7disease (Peronospora parasitica),

[0273] 25 sclerotinia rot disease (Sclerotinia sclerotiorum), black spot disease (Alternaria brassicicola), gray7mold disease (Botrytis cinerea), and the like.

[0274] Common bean: sclerotinia rot disease (Sclerotinia sclerotiorum), gray mold disease (Botrytis cinerea}, anthracnose (Colletotrichum lindemuthianum), angular spot disease (Phaeoisariopsis griseold), and the like.

[0275] 30 Apple: powdery mildew disease (Podosphaera leucotrichd), scab disease (Venturia inaequalis), Monilinia disease (Monilinia malt), black spot disease (Mycosphaerella pomi), valla canker disease (Valsa mali), alternaria blotch disease (Alternaria mail), rust disease (Gymnosporangium yamadae), ring rot disease (Botryosphaeria berengeriana), anthracnose disease (Glomerella cingulata, Colletotrichum acutatum}, leaf rot disease (Diplocarpon mali), fly speck disease (Zygophiala jamaicensis), Sooty7blotch

[0276] 32 (Gloeodes pomigena), violet root rot disease (Helicobasidium mompa), gray mold disease (Botrytis cinerea), and the like.

[0277] Japanese apricot: scab disease (Cladosporium carpophilum), gray mold disease (Botrytis cinerea), brown rot disease (Monilinia mumecola), and the like.

[0278] 5 Persimmon: powdery mildew disease (Phyllactinia kakicola), anthracnose disease (Gloeosporium kaki), angular leaf spot (Cercospora kaki), and the like.

[0279] Peach: brown rot disease (Monilinia fructicola), scab disease (Cladosporium carpophilum), phomopsis rot disease (Phomopsis sp.), bacterial shot hole disease (Xanthomonas campestris pv. pruni), and the like.

[0280] 10 Almond: brown rot disease (Monilinia taxa), spot blotch disease (Stigmina carpophila), scab disease (Cladosporium carpophilum), red leaf spot disease (Polystigma rubrum), altemaria blotch disease (Alternaria alternata), anthracnose (Colletotrichum gloeospoides), and the like.

[0281] Yellow peach: brown rot disease (Monilinia fructicola), anthracnose disease (Colletotrichum acutatum), black spot disease (Alternaria sp.), Monilinia kusanoi disease (Monilinia kusanoi), and the

[0282] 15 like.

[0283] Grape: gray mold disease (Botrytis cinerea), powdery mildew' disease (Uncinula necator), ripe rot disease (Glomerella cingulata, Colletotrichum acutatum), downy mildew disease (Plasmopara vllicold), anthracnose disease (Elsinoe ampelina), brown spot disease (Pseudocercospora vitis), black rot disease (Guignardia bidwellii), w'hite rot disease (Coniella castaneicola), rust disease (Phaknpsora

[0284] 20 ampelopsidls), and die like.

[0285] Pear: scab disease (Venturia nashicola), rust disease (Gymnosporangium asiaticum), black spot disease (Alternaria kikuchiana), ring rot disease (Botryosphaeria berengeriana), powdery mildew disease (Phyllactinia malt), Cytospora canker disease (Phomopsis fukushii), brown spot blotch disease (Stemphylium vesicarium), anthracnose disease (Glomerella cingulata), and the like.

[0286] 25 Tea: ring spot disease (Pestalotiopsis longiseta, P. theae), anthracnose disease (Colletotrichum theae-sinensis), Net blister blight (Exobasidium reticulatum), and the like.

[0287] Citrus fruits: scab disease (Elsinoe fawcettii), blue mold disease (Penicillium italicum), common green mold disease (Penicillium digitatum), gray mold disease (Botrytis cinerea), melanose disease (Diaporthe citri), canker disease (Xanthomonas campestris pv. Citri), powdery mildew disease (Oidium

[0288] 30 sp.), and the like.

[0289] Wheat: powdery mildew' (Blumeria graminisf. sp. tritici), red mold disease (Gibberella zeae), brown rust disease (Puccinia recondita), brown snow mold disease (Pythium iwayamai), pink snow mold disease (Monographella nivalis), eye spot disease (Pseudocercosporella herpotrichoides), leaf scorch disease (Septaria tritici), glume blotch disease (Leptosphaeria nodorum), typhula snow blight disease

[0290] 33 (Typhula incamata), sclerotinia snow blight disease (Myriosclerotinia borealis), damping-off disease (Gaeumannomyces graminis), ergot disease (Claviceps purpurea), stinking smut disease (Tilletia caries), loose smut disease (Ustilago nuda), and the like.

[0291] Barley: leaf spot disease (Pyrenophora graminea), net blotch disease (Pyrenophora teres), leaf

[0292] 5 blotch disease (Rhynchosporium secalis), loose smut disease (Ustilago tritici. U. nuda), and the like.

[0293] Rice: blast disease (Pyricularia oryzae), sheath blight disease (Rhizoctonia solani), bakanae disease (Gibberellafujikuroi), brown spot disease (Cochliobolus miyabeanus), damping-off disease (Pythium graminicola), bacterial leaf blight (Xanthomonas oryzae), bacterial seedling blight disease (Burkholderia plantarii), brown stripe disease (Acidovorax avenae), bacterial grain rot disease

[0294] 10 (Burkholderia glumae), Cercospora leaf spot disease (Cercospora oryzae), false smut disease (Ustilaginoidea virens), rice brown spot disease (Alternaria altemata, Curvularia intermedia), kernel discoloration of rice (Alternaria padwickii), pink coloring of rice grains (Epicoccum purpurascens), and the like.

[0295] Tobacco: sclerotinia rot disease (Sclerotinia sclerotiorum), powdery mildew disease (Erysiphe

[0296] 15 cichor acearum), phytophthora rot disease (Phytophthora nicotianae), and the like.

[0297] Tulip: gray mold disease (Botrytis cinerea), and the like.

[0298] Sunflower: downy mildew disease (Plasmopara halsledii), sclerotinia rot disease (Sclerotinia sclerotiorum), and the like.

[0299] Bent grass: Sclerotinia snow blight (Sclerotinia borealis). Large patch (Rhizoctonia solani).

[0300] 20 Brown patch (Rhizoctonia solani), Dollar spot (Sclerotinia homoeocarpa), blast disease (Pyricularia sp.), Pythium red blight disease (Pythium aphanidermatum), anthracnose disease (Colletotrichum graminicola). and tire like.

[0301] Orchard grass: powders' mildew disease (Erysiphe graminis), and the like.

[0302] Soybean: purple stain disease (Cercospora kikuchii), downy mildew disease (Peronospora

[0303] 25 manshurica), phytophthora rot disease (Phytophthora sojae), rust disease (Phakopsora pachyrhizi), sclerotinia rot disease (Sclerotinia sclerotiorum), anthracnose disease (Colletotrichum truncatum), gray mold disease (Botrytis cinerea), Sphaceloma scab (Elsinoe glycines), melanoses (Diaporthe phaseolorum var. sojae), and the like.

[0304] Potato: hytophthora rot disease (Phytophthora infestans), early blight disease (Alternaria solani),

[0305] 30 scurf disease (Thanatephorus cucumeris), verticillium wilt disease (Verticillium albo-atrum, V. dahlia, V. nigrescens, and the like.

[0306] Banana: Panama disease (Fusarium oxysporum), Sigatoka disease (Mycosphaerella fijiensis, M. musicola), and the like.

[0307] Rapeseed: sclerotinia rot disease (Sclerotinia sclerotiorum), root rot disease (Phoma lingam).

[0308] 34 black leaf spot disease (Alternaria brassicae), and the like.

[0309] Coffee: rust disease {Hemileia vastatrix), anthracnose (Colletotrichum coffeanum), leaf spot disease (Cercospora coffeicola), and the like.

[0310] Sugarcane: brown rust disease (Puccinia melanocephala), and the like.

[0311] 5 Corn: zonate spot disease (Gloeocercospora sorghi), rust disease (Puccinia sorghi), southern rust disease (Puccinia polysora), smut disease (Ustilago maydis), brown spot disease (Cochliobolus heierostrophus), northern leaf blight (Setosphaeria turcica), and the like.

[0312] Cotton: seedling blight disease (Pythium sp.), rust disease (Phakopsora gossypii), sour rot disease (Mycosphaerella areola), anthracnose (Glomerella gossypii), and the like.

[0313] 10

[0314] IV. Pesticides

[0315] The presently disclosed compounds, including compounds according to Formulas (I), (la), (lb), (Ic) and / or (II), are useful for enhancing the effect of a variety of agrochemicals, including fungicides, antiviral agents, bactericides, herbicides, insecticidal / acaricidal agents, molluscicides, nematicides, soil

[0316] 15 pesticides, plant control agents, synergistic agents, fertilizers and soil conditioners.

[0317] In one embodiment, the presently disclosed compounds are useful for enhancing the fungicidal effect of a variety of fungicides. Fungicides for use with the presently disclosed compounds, such as a compound of Formulas (I), (la), (lb), (Ic) and / or (11), are well known to those of skill in the ait and include, without limitation those set forth by class in Table 2:

[0318] Fungicides are cataloged more broadly by the Fungicide Resistance Action Committee (FRAC) in the FRAC Code List 2022 and reproduced in Appendix 1 and which is incorporated herein by reference in its entirely.

[0319] 5 In one embodiment, a presently disclosed enhancer compound, such as a compound of Formulas (I), (la), (lb), (Ic) and / or (II), is used in combinati on with one or more compound from the Families or Groups set forth in Table 2, Appendix 1, or both. In certain embodiments, a presently disclosed enhancer is used in combination with one or more fungicides recited in column 1 of Table 2.

[0320] In particular embodiments, a disclosed enhancer is used in combination with one or more of a

[0321] 10 fungicide selected from the benzimidazoles, dicarboximides, phenylpyrroles, anilinopyrimidines, hydroxyanilides, carboxamides, phenyl amides, phosphonates, cinnamic acids, oxysterol binding protein inhibitors (OSBPI), triazole carboxamides, cymoxanil, carbamates, benzamides, demethylation inhibiting piperazines, demethylation inhibiting pyrimidines, demethylation inhibiting azoles, including imidazoles,

[0322] 40 and triazoles, such as cyproconazole, difenoconazole, fenbuconazole, flutriafoL mefentrifluconazole, metconazole, ipconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, morpholines, cyflufenamid, metrafenone, pyriofenone, strobilurins, copper ammonium complex, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, lime sulfur,

[0323] 5 ethylenebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinam and thiazolidines.

[0324] Particular fungicides that are potentiated by use in combination with an enhancer according to the methods herein by administration of an apyrase inhibitor are coppers, such as copper octanoate, copper hydroxide and the like, myclobutanil, propiconazole, tebuconazole, epoxiconazole, difenoconazole,

[0325] 10 triticonazole, and prothioconazole.

[0326] In one embodiment, the combined treatment with a selected fungicide and an enhancer according to tire present disclosure, such as a compound of Formulas (I), (la), (lb), (Ic) and / or (II), provides synergistic fungicidal activity against plant pathogenic fungi.

[0327] In one embodiment, the disclosure provides compositions and methods of treating plants or plant

[0328] 15 seeds infected with or at risk of being infected with a fungal pathogen. In one embodiment compositions of the present disclosure comprise a formulation of a fungicide, an enhancer and a phytologically acceptable carrier. In another embodiment, the fungicide and enhancer are administered in separate compositions. In further embodiments, an agricultural or horticultural fungicide is used in combination with other compounds in addition to the presently disclosed apyrase inhibitors. As with the apyrase

[0329] 20 inhibitors, such other compounds can be administered in the same or separate compositions as the fungicide. Examples of the other components include known carriers to be used to conduct formulation. Additional examples thereof include conventionally -known herbicides, insecticidal / acaricidal agents, nematodes, soil pesticides, plant control agents, synergistic agents, fertilizers, soil conditioners, and animal feeds. In one embodiment, the inclusion of such other components yields synergistic effects on

[0330] 25 crop growth.

[0331] In one embodiment, the presently disclosed compounds, including compounds according to Formulas (I), (la), (lb), (Ic) and (II), are used to potentiate the effect of a herbicide. Exemplary herbicides for use in combination with the present compounds are known to those of skill in the art and include, without limitation, those described in Appendix 2. By wray of example, suitable herbicides for

[0332] 30 use in combination with the present compounds include inhibitors of acetyl CoA synthase, inhibitors of acetolactate synthesis, inhibitors of microtubule assembly, inhibitors of microtubule organization, auxin mimics, photosynthesis inhibitors, deoxy-D-xylulose phosphate synthase inhibitors, enolpyruvyl shikimate phosphate synthase inhibitors, phytoene desaturase inhibitors, glutamine synthetase inhibitors, dihydropteroate synthesis inhibitors, protoporphyrinogen oxidase inhibitors, cellulose synthesis

[0333] 41 inhibitors, uncouplers, hydroxyphenyl pyruvate dioxygenase inhibitors, fatty acid thioesterase inhibitors, serine-threonine protein phosphatase inhibitors, solanesyl diphosphate synthase inhibitors, inhibitors of very long-chain fatty acid synthesis, homogentisate solanesyl transferase inhibitors, lycopene cyclase inhibitors,

[0334] 5 In one embodiment, the presently disclosed compounds, including compounds according to Formulas (I), (la), (lb), (Ic) and / or (II), are used to potentiate the effect of an insecticide. Exemplary insecticides for use in combination with the present compounds are known to those of skill in the art and include, without limitation, those described in Appendix 3.

[0335] 10 V. Formulations

[0336] The present disclosure provides specific apyrase inhibitors, such as compounds of Formulas (I), (la), (lb), (Ic) and / or (II), to enhance tire potency' of pesticides to effectively restrict the growth of plant pathogenic species. In certain non-limiting embodiments, the apyrase inhibitors can be provided at: from about 0.01 to about 80% weight to weight in a final composition, or fiom about 25% to about 55%, such

[0337] 15 as from about 30% to about 50%, from about 35% to about 45%, such as about 0.01, 0.05, 0.1, 0.5, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.5, 3.0, 4.0, 5.0, 7.5, 10, 20, 30, 40, 50, 55, 60 or 80% w eight to weight in a final composition. In one embodiment the apyrase inhibitors are provided in liquid form at from about 0.01 to about 50%, such as from about 15% to about 50%, from about 20% to about 45%, from about 25% to about 40%, such as about 0.01 , 0.05, 0.1 , 0.5, 1.0, 1 .1 , 1 .2, 1.3, 1 .4, 1 .5, 1.6, 1 .7,

[0338] 20 1.8, 1 .9, 2.0, 2.5, 3.0, 4.0, 5.0, 7.5, 10, 15, 20, 30, 40 or 50% volume to volume in a. final diluted composition. The skilled artisan will recognize that the formulation of the pesticide, the apyrase inhibitor or a combination thereof can be provided in a concentrate that can be diluted prior to use, or can be provided in a. diluted form ready for treatment.

[0339] The enhancer, pesticide and combinations thereof are not particularly limited by the dosage form.

[0340] 25 Examples of the dosage form include wettable powders, emulsions, emulsifiable concentrates, oil- dispersible liquids, powders, granules, water-soluble agents, suspensions, granular w'ettable powders, and tablets. The method for preparing formulation is not particularlyl imited, and conventionally-known methods may be adopted depending on the dosage form.

[0341] Several formulation examples are described below. The preparation formulations shown below

[0342] 30 are merely examples, and may be modified within a range not contrary to the essence of the present disclosure. For example, additional active and inert components may be added to the formulations below7.

[0343] "Part" means "part by mass" unless otherwise specified.

[0344] 42 Formulation Example 1: Wettable Powders

[0345] 40 parts of an enhancer disclosed herein, 53 parts of diatomaceous earth, 4 parts of ethoxylated higher alcohol sulfate ester combined with a suitable solid carrier such as magnesium sulfate, and 3 parts of

[0346] 5 alkyl naphthalene sulfonate are mixed uniformly, and then finely pulverized to obtain wettable powders containing 40 parts by mass of the enhancer.

[0347] Formulation Example 2: Emulsifiable Concentrates

[0348] 10 3 parts of an enhancer disclosed herein, 60 parts of mixed petroleum distillates, 27 parts of dimethyl lactamide, and 10 pails of tristyrylphenol ethoxylates are mixed and dissolved to obtain an emulsifiable concentrate containing 3% by mass of the enhancer.

[0349] Formulation Example 3: Granules

[0350] 15

[0351] 5 parts of an enhancer disclosed herein, 10 parts of talc, 38 parts of clay, 10 parts of bentonite, 30 parts of sodium lignosulfonate and 7 parts of sodium alkyl sulfate are mixed uniformly, and then finely pulverized, followed by conducting fluidized bed granulation to make the median particle diameter thereof be 0.2 to 2.0 mm, and thus granules containing 5% by mass of an enhancer on a dry weight basis

[0352] 20 disclosed herein are obtained.

[0353] Formulation Example 4: Granules

[0354] 5 parts of an enhancer disclosed herein, 73 parts of clay, 20 parts of bentonite, 1 part of sodium dioctyl

[0355] 25 sulfosuccinate, and 1 part of potassium phosphate are mixed and then pulverized, followed by adding water thereto, and then kneading the mixture. Then, extrusion granulation is conducted, and the resultant is dried to obtain granules containing 5% by mass of the enhancer on a dry weight basis.

[0356] Formulation Example 5: Suspensions

[0357] 30

[0358] 10 parts of an enhancer disclosed herein, 4 parts of polyoxyethylene alkyl ether, 2 parts of 3 kDa sodium poly carboxylate as dispersant, 10 parts of glycerin, 0.2 parts of xanthan gum, 0.1 parts of biocides as stabilizer, 0.1 parts of organosilicone antifoam emulsion and 73.6 parts of water are mixed, and then wet pulverized until the particle size is 3 microns or less to obtain a suspension containing 10% by mass of

[0359] 43 the enhancer.

[0360] Formulation Example 6: Oil Dispersible Concentrates

[0361] 5 40 parts of an enhancer disclosed herein, 5 parts of Atlox 4914, 5 parts of organo-modified bentonite and 50 parts of methylated rapeseed oil as carrier are mixed uniformly and then wet pulverized until the median particle size is 3 microns or less to obtain an oil dispersible concentrate containing 40% by mass of the enhancer.

[0362] The skilled artisan will recognize that the various compositions are used commercially at varying

[0363] 10 concentrations and formulations. For example, it is common for fungicides to be formulated as liquids commercially at 10 - 40% concentrations. In one embodiment, the presently disclosed enhancers allow the use of a lower amount of a given fungicide due to the enhanced efficacy of fungicide in combination with an enhancer disclosed herein.

[0364] 15 VI. Methods for Assessing Enhancer Activity

[0365] Method 1: Apyrase Inhibition Assay

[0366] Apyrase inhibitors useful as enhancers of pesticidal activity are assessed using an in vitro assay. The method of Windsor, Bio Techniques 33; 1024-1030 (November 2002) was used as follows

[0367] 20 Screen for Apyrase Inhibitors -

[0368] 96 well plates were used for the assay: (Greiner bio-one: REF- 655901- 96 well, PS, F-bottom, Clear, Non-binding)

[0369] 25 Buffers:

[0370] Reaction Buffer: 60mM Hepes; 3mM MgCl2, 3mM CaChand 3mM ATP (pH 6.5)

[0371] Development Buffer A: 2% aqueous ammonium molybdate

[0372] Development Buffer B: 11% ascorbic acid in 37.5% TCA in water

[0373] Stop buffer C: 2% trisodium citrate in 2% acetic acid solution in water

[0374] 30

[0375] • Add 100 p l of reaction buffer to each well.

[0376] 44 Add 10μl of DMSO (control) or inhibitor / compound or compounds such as N1915 or orthovanadate to each well, (use inhibitor cone at ImM; orthovanadate at 2mM and N1915 at ImM)

[0377] 5 Add 10μl of apyrase (concentration based on optimization - Dilute 1 U / μl enzyme to different concentrations such as 0.1U, 0.05U, 0.0025, 0.001U, 0.0005U- to find a good range)

[0378] Incubate plate at room temperature for 1 hr

[0379] 10 Mix development buffer A and B in the ratio of 1: 1.5 (just before use).

[0380] Add 50ul of A:B mix in each well (incubate for 2 mins)

[0381] Add 50ul of C in each well

[0382] 15

[0383] Measure / Read Absorbance of plate @630nm

[0384] Inhibitory data for the apyrase assay described above are provided for selected compounds in Table 3. In Table 3, D indicates inhibition of < 10%, C indicates inhibition of from 10% to 20%, B indicates

[0385] 20 inhibition of from 20% to 30%, and A indicates inhibition above 30%:

[0386] With reference to Table 3, percent inhibition of apyrase is reported as the rounded average of at least two assay results.

[0387] 5 Method 2: In vitro Assessment of Combination Activity

[0388] Selected compounds are assessed in combination with fungicides against a range of commercially important plant pathogenic fungi.

[0389] The test is conducted as follows. A fungicide is applied to a fungal plant pathogen at a rate slightly below that at which it gave any control, in combination with a suitable dose of tire test

[0390] 10 compound. The test compound is recorded as active if control of the pathogen is observed.

[0391] 47 In more detail, the test is conducted as follows. For each combination of fungicide, pathogen and test compound, the following wells are used. Well 1 contains a fungal pathogen growing on agar, and a fungicide at a rate just below that at which it gives any control of the pathogen. Well 2 is the same as Well 1, except that the test compound is also added at Rate 1. Well 3 is the same as Well 2, except that

[0392] 5 the test compound is added at Rate 2, where Rate 2 was higher than Rate 1. Finally, as a benchmark, Well 4 is the same as Well 1 , except that it contains the fungicide at a higher rate, at which it gives partial control of the pathogen. Each of the Wells 1 to 4 are run in duplicate, giving a total of 8 wells for each combination of fungicide, pathogen and test compound. For each well, after a suitable period of incubation, a visual assessment of the % control of the pathogen by the fungicide is made. Test

[0393] 10 compounds are scored as inactive, active or highly active.

[0394] The following fungicides are used in this assay: azoxystrobin, fluxapyroxad, and desthio prothioconazole. The following fungal pathogens are used in this assay': First, a strain of Zymoseptoria tritici with a reduced susceptibility to strobilurin fungicides; second a strain of Zymoseptoria tritici with a reduced susceptibility to SDHI fungicides (i.e., those that inhibit succinate dehydrogenase): and third,

[0395] 15 Microdochium nivale. In this assay, Roux Compound 13 exhibits activity in only one combination, enhancing the activity of azoxystrobin against Microdochium nivale, but failing to enhance activity of any fungicide against either of the Zymoseptoria tritici strains. In contrast, present compounds are effective in the combination assay.

[0396] 20 Method 3: Greenhouse Crop Tests

[0397] In this method, exemplary' compounds were evaluated for their ability to control Brown Rust (Puccinia recondita?) on wheat, in a controlled greenhouse environment in combination with one of four fungicides, Amistar, Imtrex, Proline or Balaya In these studies, JB Diego wheat plants were used. Seeds were sown in 9cm diameter pots to a depth of 1 to 2 cm using Petersfield potting compost (75% medium

[0398] 25 grade peat, 12% screened sterilized loam, 3% medium grade vermiculite, 10% grit (5mm screened, lime free), 1.5 kg PG mix per m3, lime to pH5.5-6.0 and wetting agent (Vitax Ultrawet 200 ml per m3) and germinated / grown at 23C under a 16 h day / 8 h night light regime. Plants were treated two to three weeks after sowing when they were at the BBCH 1 1 growth stage (first pair of true leaves (unifoliate) unfolded). Plants were inoculated with the Puccinia triticina (Brown rust on wheat plants) 24 hours after

[0399] 30 treatment. A track sprayer was used to treat the plants with the mixture of commercial fungicide and test compound using a water volume of 200 L / ha. Four repli cates were used for each combination of fungicide and test compound. Each plant was evaluated at fourteen day's (once the disease symptoms w'ere fully expressed) for % control of the disease. Appropriate controls were used for all experiments, including an ‘inoculation check’ wherein plants were inoculated with their specific pathogen to assess

[0400] 48 disease levels. Also, each commercial fungicide was tested on its own as a part of each treatment, this being benchmark against which the experimental compounds were evaluated. Exemplar,7compounds demonstrated enhanced disease control in combination with fungicides as compared to disease control observed with fungicide alone. That is, the present compounds, although not fungicidal by themselves,

[0401] 5 enhance the activity of fungicides, thus the enhancer compounds work synergistically in combination with fungicides to control disease.

[0402] In these studies the fungicide was applied at the following rates

[0403] In this method, wnrking examples enhanced the activity of Amistar against Brown Rust on wheat by

[0404] 10 significant amounts relative to die activity of Amistar alone. Compounds 1-1, 1-14, 1-63 and 1-67 all provided greater than 50% additional disease control benefit in combination with Amistar over Amistar alone. Compounds 1-3, 1-5 and 1-6 provided greater than 30% additional Brown Rust control relative to Amistar alone, and compound 1-66 provided greater than 20% additional Brown Rust control in combination with Amistar over Amistar alone.

[0405] 15 Working examples also enhanced the activity of Imtrex against Brown Rust on wheat by significant amounts relative to Imtrex treatment alone. For example, compounds 1-1 and 1-67 provided greater than 50% additional disease control benefit in combination witli Imtrex over Imtrex alone. Compounds 1-13, 1-63 and 1-3 provided greater than 30% additional Brown Rust control relative to Imtrex alone, and compounds 1-5 and 1-66 provided greater than 15% additional Brown Rust control in

[0406] 20 combination with Imtrex over Imtrex alone.

[0407] Working examples 1-6, 1-14 and 1-67 enhanced the activity of Balaya against Brown Rust on wheat by over 50% over Balaya alone. Working examples 1-66 and 1-63 each provided greater than 30% additional Brown Rust control benefit in combination with Balaya over Balaya alone. Compounds 1-1 and 1-5 provided greater than 20% additional Brown Rust control in combination with Balaya over

[0408] 25 Balaya alone. Compound 1-3 provided measurable additional Brown Rust control in combination with Balaya over Balaya alone.

[0409] The Brown Rust isolate used in this method is resistant to Proline and no control was observed with Proline alone at the application rate of 0.15 L / hectare. Exemplary compounds showed some control in combination with Proline applied at 0.15 L / hectare and in these examples Brown Rust control was

[0410] 30 observed to be comparable to that achieved with 0.72 L / hectare Proline alone.

[0411] Method 4: Enhancement of Herbicide Activity

[0412] 49 This method demonstrates the enhancement of herbicidal activity provided by the present compounds. Specifically, Amaranthus retroflexus (pigweed) was treated pre-emergence with metribuzin alone or in combination xvith an enhancer compound disclosed herein. Fifteen seeds of Amaranthus retroflexus were sown in soil in each pot and then sprayed with a mixture of metribuzin at the appropriate

[0413] 5 rate shown in Table 4 and the compound of this invention at 100 g / ha using a track sprayer at a water volume of 200 L / hectare. Small amounts of acetone were used to aid solubility. The pots were watered immediately after sowing and treatment and then allowed to stand in a glasshouse. Assessment of kill was made seven and fourteen days after treatment. The test included four replicates for each treatment and the control. Results are shown in Table 4. Exemplary compounds 1-14 and 1-63 demonstrated

[0414] 10 significant enhancement of metribuzin herbicidal activity at seven and fourteen days.

[0415] Table 4. Pre-Emergence Amaranthus Kill Percentage

[0416] VII. Methods for Making Enhancer Compounds

[0417] 15 Exemplary7enhancer compounds were purchased from commercial suppliers, such as Enamine, located at Industriepark Hoechst, G837. 65926 Frankfurt am Main Germany.

[0418] Compounds disclosed herein, including compounds of Formulas (1), (la), (lb), (1c) and (II), can be prepared as will be understood by those of skill upon consideration of the present disclosure. For example, compounds containing a carboxamide group can be prepared by the reaction between an amine

[0419] 20 and a carboxylie acid that has been activated in some way, in a suitable solvent and at a suitable temperature. For example, a carboxylic acid can be activated by converting it into die corresponding carboxylic acid halide, such as an acid bromide or chloride; reaction with an amine then gives the required carboxamide together with an acid, such as hydrobromic or hydrochloric acid, which is usually7

[0420] 50 neutralized by a base, such as a tertian- amine base in the reaction mixture. Examples of methods that can be used to synthesize compounds of the invention are described in ACS Sustainable Chemistry & Engineering 2022, 10, 16046-16054 and in Journal of Medicinal Chemistry 2016, 59, 6512-6530 which describes the reaction of carboxylic acid chloride groups with primary or secondary amines to yield the

[0421] 5 corresponding amide compounds.

[0422] Reaction of dicarboxylic acid compounds with a first amine followed by reaction of the second carboxylic acid moiety with a second amine to form bis-carboxamide compounds is described in, for example. International App. Pub. Nos. WO 2008 / 008234 and WO 99 / 43651 and Zhurnal Organicheskoi Khimii 1988, 24(9), 1968-72. These methods can be used as will be recognized by those of skill in tire art

[0423] 10 of organic synthesis upon consideration of the present disclosure, in particular the the methods set forth below-:

[0424] Synthesis of enhancer compounds

[0425] 15

[0426] Scheme 1 illustrates a suitable preparation for symmetrical compounds of Formula (I) disclosed herein (for example wherein compounds have R1= R2and R3= R4). In addition to the reagents shown in the scheme, an amine of formula R'R3NH is used (for the symmetrical product compounds, this is equivalent to the amine R2R4NH) See, ACS Sustainable Chemistry & Engineering 2022, 10, 16046-

[0427] 20 16054 and \n Journal of Medicinal Chemistry 2016, 59, 6512-6530 which describes the reaction of carboxylic acid chloride groups with primary' or secondary amines to yield the corresponding amide compounds

[0428] Furthermore, the chemistry shown in Scheme 1 can be used to make unsymmetrical compounds of Formula (I), by treatment first with an amine of formula R1R3NH, together with the reagents shown in

[0429] 25 Scheme 1, and then with an amine of formula R2R4NH, together with the reagents shown in Scheme 1. Various methods can be used to minimize over-reaction at the first step, e.g., slow addition of the amine R1R3NH to a stirred mixture of the other reactants. Chemistry parallel to that shown in Scheme 1 can be used to make ortho- and para-substituted compounds of Formula (I) by using the corresponding ortho- or ^ra-substituted bis-acid chloride as starting material.

[0430] 51

[0431] Scheme 2 illustrates two sequential amide bond forming reactions using coupling agents, such as those selected from the carbodiimides, such as DCC (dicyclohexyl carbodiimide), EDCI (l-Ethyl-3-(3-

[0432] 5 dimethylaminopropyl) carbodiimide hydrochloride), or the like, carbonyldiimidazole, phosphonium salt reagents, such as BOP, PyBOP, PyBrOP and the like, and uronium salt reagents, such as HBTU, HATH, and the like. Additional coupling reagents are known to those of skill in the art and can be selected upon consideration of the schemes and compounds illustrated herein. The amide bond forming techniques of Scheme 2 also are applicable to th e ortho and para analogs of the meta diacid, amide an d di amide

[0433] 10 compounds illustrated therein. Additional reagents and techniques consistent with Scheme 2, will be readily apparent to those of skill in the art upon consideration of the present disclosure and further in view' of International App. Pub. Nos. WO 2008 / 008234 and WO 99 / 43651 and Zhurnal Organicheskoi Khimii 1988, 24(9), 1968-72.

[0434] An alternative preparation of ortho diamide compounds is illustrated in Scheme 3:

[0435] 15

[0436] With continued reference to Scheme 3, tire first step finds precedent in Journal of Organic Chemistry 2001, 66, 1548-1552, Bioorganic & Medicinal Chemistry Leiters 2001, 11, 2671-2674, and Indian

[0437] 20 Journal of Chemistry, Section B: Organic Chemistry7Including Medicinal Chemistry' 1998, 37B, 704- 706. 'flie second step is a conventional coupling reaction that can be conducted as is well known to those of skill in the art and consistent with the techniques used in Scheme 2.

[0438] Schemes 4 - 6 illustrate preparation of dihydrophthalazine-1, 4-dione compounds:

[0439] 25 Scheme 4 is further illustrated by Chemische Berichte 1985, 118, 4404-14.

[0440] With reference to Scheme 5, R may be any suitable group, such as hydrogen, alkyl or other group as will

[0441] 5 be appreciated by those of skill in the art. See also, Chemistry - A European Journal 2018, 24, 590-593.

[0442] With reference to Scheme 6, the reaction can be performed in one step when R1and R2are the same, or optionally in two steps when R1and R2are different.

[0443] 10 With reference to Schemes 1 - 6, the groups R1, R2, R3, R4and Z are as described herein throughout.

[0444] 53

[0445]

[0446] 62

[0447] APPENDIX 2

[0448] MODE OF ACTION CHEMICAL CLASSIFICATION ACTIVE

[0449] Inhibition of Acetyl CoA

[0450] Carboxylase Cyclohexanediones (DI Ms) Alloxydim

[0451] Inhibition of Acetyl CoA

[0452] Carboxylase Cyclohexanediones (DI Ms) Butroxydim

[0453] Inhibition of Acetyl CoA

[0454] Carboxylase Cyclohexanediones (DI Ms) Clethodim

[0455] Inhibition of Acetyl CoA

[0456] Carboxylase Cyclohexanediones (DI Ms) Cloproxydim

[0457] Inhibition of Acetyl CoA

[0458] Carboxylase Cyclohexanediones (DI Ms) Cycioxydim

[0459] Inhibition of Acetyl CoA

[0460] Carboxylase Cyclohexanediones (DI Ms) Profoxydim

[0461] Inhibition of Acetyl CoA

[0462] Carboxylase Cyclohexanediones (DI Ms) Sethoxydim

[0463] Inhibition of Acetyl CoA

[0464] Carboxylase Cyclohexanediones (DI Ms) Tepraloxydim

[0465] Inhibition of Acetyl CoA

[0466] Carboxylase Cyclohexanediones (DI Ms) i ralkoxydim

[0467] Inhibition of Acetyl Co A Aryloxy phenoxy-propionates Carboxylase (FOPs) Clodinafop-propargyi inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Clofop

[0468] Inhibition of Acetyl CoA Aryloxyohenoxy-propionates

[0469] Carboxylase (FOPs)' Cyhalofop-butyi

[0470] Inhibition of Acetyl CoA Aryloxyphenoxy-propionates

[0471] Carboxylase (FOPs) Diclofop-methyl

[0472] Inhibition of Acetyl CoA Aryloxyphenoxy-propionates

[0473] Carboxylase (FOPs)' Fenoxaprop-ethyl inhibition of Acetyl CoA Aryloxyohenoxy-propionates

[0474] Carboxylase (FOPs)' Fenthiaprop

[0475] Inhibition of Acetyl CoA Aryloxyphenoxy-propionates

[0476] Carboxylase (FOPs)' Fluazifop-butyl

[0477] Inhibition of Acetyl CoA Aryloxyphenoxy-propionates

[0478] Carboxylase (FOPs) Haloxyfop-methyl

[0479] Inhibition of Acetyl CoA Aryloxyphenoxy-propionates

[0480] Carboxylase (FOPs) Isoxapyrifop

[0481] Inhibition of Acetyl CoA Aryloxyohenoxy-propionates

[0482] Carboxylase (FOPs)' Metamifop

[0483] Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Quizalofop-ethyl inhibition of Acetyl Co A Carboxylase Phenylpyrazoline Pinoxaden

[0484] Inhibition of Acetolactate Synthase Pyrimidinyl benzoates Bispyribac-sodium

[0485] 69 Inhibition of Acetolactate Pyribenzoxim (prodrug of

[0486] Synthase Pyrimidinyl benzoates bispyribac)

[0487] Inhibition of Acetolactate

[0488] Synthase Pyrimidinyl benzoates Pyriftalid

[0489] Inhibition of Acetolactate

[0490] Synthase Pyrimidinyi benzoates Pyriminobac-methyi

[0491] Inhibition of Acetolactate

[0492] Synthase Pyrimidinyl benzoates Pyrithiobac-sodium inhibition of Acetolactate

[0493] Synthase Sulfonanilides Pyrimisulfan

[0494] Inhibition of Acetolactate

[0495] Synthase Sulfonanilides Triafamone

[0496] Inhibition of Acetolactate

[0497] Synthase Triazoiopyrimidine - Type 1 Cloransulam-methyl

[0498] Inhibition of Acetolactate

[0499] Synthase Triazoiopyrimidine - Type 1 Diclosulam inhibition of Acetolactate

[0500] Synthase Triazoiopyrimidine - Type 1 Florasulam

[0501] Inhibition of Acetolactate

[0502] Synthase Triazoiopyrimidine - Type 1 Flumetsulam

[0503] Inhibition of Acetolactate Triazoiopyrimidine - Type 1

[0504] Synthase Metosulam

[0505] Inhibition of Acetolactate Triazoiopyrimidine - Type 2

[0506] Synthase Penoxsulam

[0507] Inhibition of Acetolactate

[0508] Synthase Triazoiopyrimidine - Type 2 Pyroxsulam

[0509] Inhibition of Acetolactate

[0510] Synthase Sulfonylureas Amidosulfuron

[0511] Inhibition of Acetolactate

[0512] Synthase Sulfonylureas Azimsulfuron

[0513] Inhibition of Acetolactate

[0514] Synthase Sulfonylureas Bensulfuron-methyl

[0515] Inhibition of Acetolactate

[0516] Synthase Sulfonylureas Chlorimuron-ethyl

[0517] Inhibition of Acetolactate

[0518] Synthase Sulfonylureas Chlorsulfuron

[0519] Inhibition of Acetolactate

[0520] Synthase Sulfonylureas Cinosulfuron

[0521] Inhibition of Acetolactate

[0522] Synthase Sulfonylureas Cyclosuifamuron inhibition of Acetolactate

[0523] Synthase Suifonylureas Ethametsulfuron-methyl

[0524] Inhibition of Acetolactate

[0525] Synthase Sulfonylureas Ethoxysulfuron

[0526] Inhibition of Acetolactate

[0527] Synthase Sulfonylureas Flazasulfuron

[0528] Inhibition of Acetolactate

[0529] Synthase Sulfonylureas Flucetosulfuron

[0530] Inhibition of Acetolactate

[0531] Synthase Sulfonylureas Flupyrsulfuron-methyl-Na

[0532] 70 Inhibition of Acetolactate

[0533] Synthase Sulfonylureas Foramsulfuron

[0534] Inhibition of Acetolactate

[0535] Synthase Sulfonylureas Halosulfuron-methy!

[0536] Inhibition of Acetolactate

[0537] Synthase Sulfonylureas Imazosulfuron inhibition of Acetolactate

[0538] Synthase Sulfonylureas lodosulfuron-methyl-Na

[0539] Inhibition of Acetolactate

[0540] Synthase Sulfonylureas Mesosulfuron-methyl

[0541] Inhibition of Acetolactate

[0542] Synthase Sulfonylureas Metazosulfuron

[0543] Inhibition of Acetolactate

[0544] Synthase Sulfonylureas Metsulfuron-methyl

[0545] Inhibition of Acetolactate

[0546] Synthase Sulfonylureas Nicosuifuron

[0547] Inhibition of Acetolactate

[0548] Synthase Sulfonylureas Orthosuifamuron inhibition of Acetolactate

[0549] Synthase Sulfonylureas Oxasulfuron

[0550] Inhibition of Acetolactate

[0551] Synthase Suifonylureas Primisulfuron-methyl

[0552] Inhibition of Acetolactate

[0553] Synthase Sulfonylureas Propyrisulfuron

[0554] Inhibition of Acetolactate

[0555] Synthase Suifonylureas Prosulfuron

[0556] Inhibition of Acetolactate

[0557] Synthase Sulfonylureas Pyrazosulfuron-ethyl inhibition of Acetolactate

[0558] Synthase Suifonylureas Rimsulfuron

[0559] Inhibition of Acetolactate

[0560] Synthase Suifonylureas Sulfometuron-methyl

[0561] Inhibition of Acetolactate

[0562] Synthase Suifonylureas Sulfosulfuron

[0563] Inhibition of Acetolactate

[0564] Synthase Suifonylureas Triasulfuron

[0565] Inhibition of Acetolactate

[0566] Synthase Suifonylureas Tribenuron-methyl

[0567] Inhibition of Acetolactate

[0568] Synthase Suifonylureas Thifensulfuron-methyl

[0569] Inhibition of Acetolactate

[0570] Synthase Suifonylureas T rifloxysulfuron-Na

[0571] Inhibition of Acetolactate

[0572] Synthase Suifonylureas T riflusulfuron-methy I

[0573] Inhibition of Acetolactate

[0574] Synthase Suifonylureas Tritosulfuron

[0575] Inhibition of Acetolactate

[0576] Synthase imidazolinones Imazamethabenz-methyl inhibition of Acetolactate

[0577] Synthase imidazoiinones Imazamox

[0578] Inhibition of Acetolactate

[0579] Synthase Imidazoiinones Imazapic

[0580] Inhibition of Acetolactate

[0581] Synthase imidazoiinones Imazapyr

[0582] 71 Inhibition of Acetolactate

[0583] Synthase Imidazoiinones Imazaquin inhibition of A.cetolactate

[0584] Synthase Imidazolinones Imazethapyr

[0585] Inhibition of Acetolactate

[0586] Synthase Triazoiinones Flucarbazone-Na

[0587] Inhibition of Acetolactate

[0588] Synthase Triazoiinones Propoxycarbazone-Na

[0589] Inhibition of Acetolactate

[0590] Synthase Triazoiinones Thiencarbazone-methyl

[0591] Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Atraton Inhbition of Photosynthesis at PSII - Serine 264 Binders T riazines Atrazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Ametryne inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Aziprotryne=aziprotryn Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Chlorazine inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines CP 17029 Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Cyanazine Inhbition of Photosynthesis at PSII - Serine 264 Binders T riazines Cyprazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Desmetryne Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Dimethametryn Inhbition of Photosynthesis at PSI! - Serine 264 Binders Triazines Dipropetryn Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Egiinazine-ethyi Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Ipazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Methoprotryne=methoprotryn Inhbition of Photosynthesis at PSII - Serine 264 Binders T riazines procyazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Proglinazine-ethyi Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Prometon Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Prometryne Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Propazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Sebuthyiazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Secbumeton

[0592] Inhbition of Photosynthesis at Triazines Simetryne

[0593] 72 PSII - Serine 264 Binders

[0594] Inhbition of Photosynthesis at PSII - Serine 264 Binders T riazines Simazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Terbumeton Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Terbuthylazine Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Terbutryne Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazines Trietazine

[0595] Inhbition of Photosynthesis at Triazolinone PSII - Serine 264 Binders Amicarbazone

[0596] Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazinones Ethiozin Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazinones Hexazinone Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazinones Isomethiozin Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazinones Metamitron Inhbition of Photosynthesis at PSII - Serine 264 Binders Triazinones Metribuzin

[0597] Inhbition of Photosynthesis at PSII - Serine 264 Binders Uracils Bromacil Inhbition of Photosynthesis at PSII - Serine 264 Binders Uracils Isocil Inhbition of Photosynthesis at PSII - Serine 264 Binders Uracils Lenacil Inhbition of Photosynthesis at PSII - Serine 264 Binders Uracils Terbacil

[0598] Inhbition of Photosynthesis at PSII - Serine 264 Binders Phenlcarbamates Chlorprocarb Inhbition of Photosynthesis at PSII - Serine 264 Binders Phenlcarbamates Desmedipham Inhbition of Photosynthesis at PSII - Serine 264 Binders Phenlcarbamates Phenisopham Inhbition of Photosynthesis at PSII - Serine 264 Binders Phenlcarbamates Phenmedipham

[0599] Inhbition of Photosynthesis at Pyridazinone PSII - Serine 264 Binders Chloridazon (-pyrazon) Inhbition of Photosynthesis at Pyridazinone PSII - Serine 264 Binders Brompy razon inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Benzthiazuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Bromuron

[0600] 73 Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Buturon Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Chlorbromuron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Chlorotoiuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Chloroxuron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Difenoxuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Dimefuron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Diuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Ethidimuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Fenuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Fluometuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Fluothiuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Isoproturon Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Isouron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Linuron inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Metobenzuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Metobromuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Methabenzthiazuron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Metoxuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Monolinuron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Monuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Neburon Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Parafluron inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Siduron Inhbition of Photosynthesis at Ureas PSII - Serine 264 Binders Tebuthiuron Inhbition of Photosynthesis at PSII - Serine 264 Binders Ureas Thiazafluron inhbition of Photosynthesis at PSII - Serine 264 Binders Amides Chloranocryl=dicryl inhbition of Photosynthesis at PSII - Serine 264 Binders Amides Pentanochior

[0601] 74 Inhbition of Photosynthesis at PSII - Serine 264 Binders Amides Propanil

[0602] Inhbition of Photosynthesis at PSII - Histidine 215 Binders Nitriles Bromofenoxim Inhbition of Photosynthesis at PSII - Histidine 215 Binders Nitriles Bromoxynil inhbition of Photosynthesis at PSII - Histidine 215 Binders Nitriles Ioxynil

[0603] Inhbition of Photosynthesis at PSII - Histidine 215 Binders Phenyl-pyridazines Pyridate

[0604] Inhbition of Photosynthesis at PSII - Histidine 215 Binders Benzothiadiazinone Bentazon

[0605] PS I Electron Diversion Pyridiniums Cyperquat

[0606] PS I Electron Diversion Pyridiniums Diquat

[0607] PS I Electron Diversion Pyridiniums Morfamquat

[0608] PS I Electron Diversion Pyridiniums Paraquat

[0609] Inhibition of

[0610] Protoporphyrinogen Oxidase Diphenyl ethers Lactofen inhibition of

[0611] Protoporphyrinogen Oxidase Diphenyl ethers Acifluorfen inhibition of

[0612] Protoporphyrinogen Oxidase Diphenyl ethers Bifenox

[0613] Inhibition of

[0614] Protoporphyrinogen Oxidase Diphenyl ethers Chlornitrofen

[0615] Inhibition of

[0616] Protoporphyrinogen Oxidase Diphenyl ethers Fomesafen inhibition of

[0617] Protoporphyrinogen Oxidase Diphenyl ethers Fluorodifen

[0618] Inhibition of

[0619] Protoporphyrinogen Oxidase Diphenyl ethers Fluoroglycofen-ethyl

[0620] Inhibition of

[0621] Protoporphyrinogen Oxidase Diphenyl ethers Fluoronitrofen

[0622] Inhibition of

[0623] Protoporphyrinogen Oxidase Diphenyl ethers Nitrofen inhibition of

[0624] Protoporphyrinogen Oxidase Diphenyl ethers Oxyfluorfen

[0625] Inhibition of

[0626] Protoporphyrinogen Oxidase Diphenyl ethers Chlomethoxyfen inhibition of

[0627] Protoporphyrinogen Oxidase Phenylpyrazoles Pyrafiufen-ethyl

[0628] Inhibition of

[0629] Protoporphyrinogen Oxidase N-Pheny!-oxadiazolones Oxadiargyl

[0630] Inhibition of

[0631] Protoporphyrinogen Oxidase N-Phenyi-oxadiazolones Oxadiazon

[0632] 75 inhibition of

[0633] Protoporphyrinogen Oxidase N-Phenyi-triazolinones Azafenidin inhibition of

[0634] Protoporphyrinogen Oxidase N-Phenyi-triazolinones Carfentrazone-ethyi

[0635] Inhibition of

[0636] Protoporphyrinogen Oxidase N-Phenyi-triazolinones Sulfentrazone inhibition of N-Phenyi-imides (procide acitive

[0637] Protoporphyrinogen Oxidase form) Fiuthiacet-methyl inhibition of

[0638] Protoporphyrinogen Oxidase N-Phenyi-imides Butafenacil

[0639] Inhibition of

[0640] Protoporphyrinogen Oxidase N-Phenyi-imides Saflufenacil inhibition of

[0641] Protoporphyrinogen Oxidase N-Phenyl-imides Pentoxazone inhibition of

[0642] Protoporphyrinogen Oxidase N-Phenyi-imides Chlorphthaiim

[0643] Inhibition of

[0644] Protoporphyrinogen Oxidase N-Phenyi-imides Cinidon-ethyi inhibition of

[0645] Protoporphyrinogen Oxidase N-Phenyi-imides Fiumiciorac-pentyl

[0646] Inhibition of

[0647] Protoporphyrinogen Oxidase N-Phenyi-imides Fiumioxazin inhibition of

[0648] Protoporphyrinogen Oxidase N-Phenyl-imides Fiumipropyn

[0649] Inhibition of

[0650] Protoporphyrinogen Oxidase N-Phenyi-imides Trifludimoxazin inhibition of

[0651] Protoporphyrinogen Oxidase N-Phenyi-imides Tiafenacii

[0652] Inhibition of

[0653] Protoporphyrinogen Oxidase Other Pyracionil inhibition of Phytoene Desaturase Phenyl ethers Beflubutamid inhibition of Phytoene

[0654] Desaturase Phenyl ethers Diflufenican

[0655] Inhibition of Phytoene Desaturase Phenyl ethers Picoiinafen inhibition of Phytoene

[0656] Desaturase N-Phenyi heteroeycles Fiurochloridone

[0657] Inhibition of Phytoene Desaturase N-Phenyi heterocycles Norflurazon inhibition of Phytoene Desaturase Diphenyl heterocycles Fiuridone

[0658] Inhibition of Phytoene Desaturase Diphenyl heterocycles Flurtamone inhibition of Hydroxyphenyi

[0659] Pyruvate Dioxygenase Triketones Mesotrione inhibition of Hydroxyphenyi

[0660] Pyruvate Dioxygenase Triketones Sulcotrione

[0661] 76 inhibition of Hydroxyphenyi Pyruvate Dioxygenase Triketones Tembotrione inhibition of Hydroxyphenyi Pyruvate Dioxygenase Triketones Tefuryltrione inhibition of Hydroxyphenyi Pyruvate Dioxygenase Triketones Bicyclopyrone inhibition of Hydroxyphenyi Pyruvate Dioxygenase Triketones Fenquinotrione Inhibition of Hydroxyphenyi Triketones (procide) Pyruvate Dioxygenase Benzobicyclon

[0662] Inhibition of Hydroxyphenyi Pyruvate Dioxygenase Pyrazoles (procide) Benzofenap inhibition of Hydroxyphenyi Pyruvate Dioxygenase Pyrazoles Pyrasulfotole inhibition of Hydroxyphenyi Pyruvate Dioxygenase Pyrazoles Topramezone inhibition of Hydroxyphenyi Pyruvate Dioxygenase Pyrazoles (procide) Pyrazolynate inhibition of Hydroxyphenyi Pyruvate Dioxygenase Pyrazoles (procide) Pyrazoxyfen Inhibition of Hydroxyphenyi Pyruvate Dioxygenase Pyrazoles Tolpyralate inhibition of Hydroxyphenyi Pyruvate Dioxygenase isoxazoles Isoxaflutole inhibition of Homogentisate Solanesyitransferase Phenoxy py ridazine Cyciopyrimorate inhibition of Deoxy-D-Xyulose Phosphate Synthase isoxazolidinone Clomazone inhibition of Deoxy-D-Xyulose Phosphate Synthase Isoxazolidinone Bixlozone inhibition of Enolpyruvyl Shikimate Phosphate Synthase Glycine Glyphosate inhibition of Glutamine

[0663] Synthetase Phosphinic acids Glufosinate-ammonium inhibition of Glutamine

[0664] Synthetase Phosphinic acids Bialaphos / bilanafos inhibition of Dihydropteroate Synthase Carbamate Asuiam inhibition of Microtubule

[0665] Assembly Dinitroanilines Benefin=benfiuralin

[0666] Inhibition of Microtubule Dinitroanilines

[0667] Assembly Butralin

[0668] Inhibition of Microtubule Dinitroanilines

[0669] Assembly Dinitramine

[0670] 77 Inhibition of Microtubule

[0671] Assembly Dinitroanilines Ethalfluralin

[0672] Inhibition of Microtubule

[0673] Assembly Dinitroanilines Fluchloralin

[0674] Inhibition of Microtubule

[0675] Assembly Dinitroanilines Isopropalin

[0676] Inhibition of Microtubule

[0677] Assembly Dinitroanilines Nitralin

[0678] Inhibition of Microtubule

[0679] Assembly Dinitroanilines Prodiamine

[0680] Inhibition of Microtubule

[0681] Assembly Dinitroanilines Profiuralin

[0682] Inhibition of Microtubule

[0683] Assembly Dinitroanilines Oryzalin

[0684] Inhibition of Microtubule

[0685] Assembly Dinitroanilines Pendimethalin

[0686] Inhibition of Microtubule

[0687] Assembly Dinitroanilines Trifluralin inhibition of Microtubule

[0688] Assembly Pyridines Dithiopyr

[0689] Inhibition of Microtubule

[0690] Assembly Pyridines Thiazopyr

[0691] Inhibition of Microtubule

[0692] Assembly Phosphoroamidates Butamifos

[0693] Inhibition of Microtubule

[0694] Assembly Phosphoroamidates DMPA

[0695] Inhibition of Microtubule Assembly Benzoic acid Chlorthal-dimethyl=DCPA

[0696] Inhibition of Microtubule Assembly Benzamides Propyzamide=pronamide

[0697] Inhibition of Microtubule

[0698] Organization Carbamates Barban

[0699] Inhibition of Microtubule

[0700] Organization Carbamates Carbetamide

[0701] Inhibition of Microtubule

[0702] Organization Carbamates Chlorbufam

[0703] Inhibition of Microtubule

[0704] Organization Carbamates Chlorpropham

[0705] Inhibition of Microtubule

[0706] Organization Carbamates Propham

[0707] Inhibition of Microtubule

[0708] Organization Carbamates Swep inhibition of Cellulose Synthesis T riazolocarboxamide Flupoxam

[0709] Inhibition of Cellulose Synthesis Benzamides Isoxaben

[0710] 78 inhibition of Cellulose

[0711] Synthesis Alkylazines Triaziflam

[0712] Inhibition of Cellulose

[0713] Synthesis Alkylazines Indazifiam

[0714] Inhibition of Cellulose

[0715] Synthesis Nitriles Dichlobenil

[0716] Inhibition of Cellulose

[0717] Synthesis Nitriles Chlorthiamid

[0718] Uncouplers Dinitrophenols Dinosam

[0719] Uncouplers Dinitrophenols Dinoseb

[0720] Uncouplers Dinitrophenols DNOC

[0721] Uncouplers Dinitrophenols Dinoterb

[0722] Uncouplers Dinitrophenols Etinofen

[0723] Uncouplers Dinitrophenols Medinoterb

[0724] Inhibition of Very Long-Chain

[0725] Fatty Acid Synthesis Azolyl-carboxamides Cafenstrole

[0726] Inhibition of Very Long-Chain

[0727] Fatty Acid Synthesis Azolyl-carboxamides Fentrazamide

[0728] Inhibition of Very Long-Chain Fatty Acid Synthesis Azolyl-carboxamides Ipfencarbazone

[0729] Inhibition of Very Long-Chain

[0730] Fatty Acid Synthesis a-Thioacetamides Amlofos Inhibition of Very Long-Chain

[0731] Fatty Acid Synthesis a-Thioacetamides Piperophos

[0732] Inhibition of Very Long-Chain

[0733] Fatty Acid Synthesis isoxazolines Pyroxasuifone Inhibition of Very Long-Chain

[0734] Fatty Acid Synthesis Isoxazolines Fenoxasuifone

[0735] Inhibition of Very Long-Chain Fatty Acid Synthesis Oxiranes Indanofan inhibition of Very Long-Chain Fatty Acid Synthesis Oxiranes Tridiphane

[0736] Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Acetochlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Alachlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Allidochlor=CDAA inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Butachlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Butenachlor

[0737] Inhibition of Very Long-Chain a-Chloroacetamides Delachlor

[0738] 79 Fatty Acid Synthesis Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Diethatyi-ethyl Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Dimethachior Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Dimethenamid Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Metazachlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Metolachlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Pethoxamid Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Pretilachlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Propachlor Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Propisochlor inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Prynachior Inhibition of Very Long-Chain Fatty Acid Synthesis a-Chloroacetamides Thenylchlor

[0739] Inhibition of Very Long-Chain Fatty Acid Synthesis a-Oxyacetamides Mefenacet inhibition of Very Long-Chain Fatty Acid Synthesis a-Oxyacetamides Flufenacet inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Butylate inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Cycloate Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Dimepiperate inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates EPTC inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Esprocarb Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Molinate Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Orbencarb Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Pebulate inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Prosulfocarb Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Thiobencarb (=Benthiocarb) Inhibition of Very Long-Chain Fatty Acid Sy nthesis Thiocarbamates Tiocarbazil inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Tri-allate inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Vernolate

[0740] 80 inhibition of Very Long-Chain Fatty Acid Synthesis Benzofurans Benfuresate inhibition of Very Long-Chain Fatty Acid Synthesis Benzofurans Ethofumesate

[0741] Auxin Mimics Pyridine-carboxylates Picloram

[0742] Auxin Mimics Pyridine-carboxylates Clopyralid

[0743] Auxin Mimics Pyridine-carboxylates Aminopyralid

[0744] Auxin Mimics Pyridine-carboxylates Halauxifen

[0745] Auxin Mimics Pyridine-carboxylates Fiorpyrauxifen

[0746] Auxin Mimics Pyridyloxy-carboxylates Triclopyr

[0747] Auxin Mimics Pyridyloxy-carboxylates Fluroxypyr

[0748] Auxin Mimics Phenoxy-carboxylates 2,4,5-T

[0749] Auxin Mimics Phenoxy-carboxylates 2.4-D

[0750] Auxin Mimics Phenoxy-carboxylates 2.4-DB

[0751] Auxin Mimics Phenoxy-carboxylates Clomeprop

[0752] Auxin Mimics Phenoxy-carboxylates Dichlorprop

[0753] Auxin Mimics Phenoxy-carboxylates Fenoprop

[0754] Auxin Mimics Phenoxy-carboxylates Mecoprop

[0755] Auxin Mimics Phenoxy-carboxylates MCPA

[0756] Auxin Mimics Phenoxy-carboxylates MCPB

[0757] Auxin Mimics Benzoates Dicamba

[0758] Auxin Mimics Benzoates Chloramben

[0759] Auxin Mimics Benzoates TBA

[0760] Auxin Mimics Quinoline-carboxylates Quinclorac

[0761] Auxin Mimics Quinoline-carboxylates Quinmerac

[0762] Auxin Mimics Pyrimidine-carboxylates Aminocyclopyrachlor

[0763] Auxin Mimics Other Benazolin-ethyl

[0764] Auxin Mimics Phenyl carboxylates Chlorfenac=fenac

[0765] Auxin Mimics Phenyl carboxylates Chlorfenprop

[0766] Auxin Transport inhibitor Aryl-carboxylates Naptalam

[0767] Auxin Transport Inhibitor Aryl-carboxylates Diflufenzopyr-sodium

[0768] Inhibition of Fatty Acid Thioesterase Benzyl ether Cinmethylin

[0769] 81 Inhibition of Fatty Acid Thioesterase Benzyl ether Methiozolin

[0770] Inhibition of Serine-Threonine Protein Phosphatase Other Endothal

[0771] Inhibition of Solanesyl Diphosphate Synthase Diphenyl ether Aclonifen

[0772] Inhibition of Lycopene Cyclase T riazoie Amitrole

[0773] Unknown Bromobutide

[0774] Unknown Cumyluron

[0775] Unknown Difenzoquat

[0776] Unknown DSMA

[0777] Unknown Dymron=Daimuron

[0778] Unknown Etobenzanid

[0779] Unknown Arylaminopropionic acid Flamprop-m

[0780] Unknown Fosamine

[0781] Unknown Methyldymron

[0782] Unknown Monalide

[0783] Unknown MSMA

[0784] Unknown Oleic acid

[0785] Unknown Oxaziciomefone

[0786] Unknown Pelargonic acid

[0787] Unknown Pyributicarb

[0788] Unknown Quinoclamine

[0789] Unknown Acetamides Diphenamid

[0790] Unknown Acetamides Naproaniiide

[0791] Unknown Acetamides Napropamide

[0792] Unknown Benzamide Tebutam

[0793] Unknown Phosphorodithioate Bensulide

[0794] Unknown Chlorocarbonic acids Dalapon

[0795] Unknown Chlorocarbonic acids Fiupropanate

[0796] Unknown Chlorocarbonic acids TCA

[0797] Unknown T rifiuoromethanesulfonanilides Mefluidide

[0798] Unknown T rifiuoromethanesulfonanilides Perfiuidone

[0799] Unknown CAMA

[0800] Unknown Cacodylic acid

[0801] 82 Notwithstanding the appended claims, aspects of the present disclosure are further provided in the following clauses:

[0802] 1. A method for inhibiting apyrase, comprising contacting the apyrase

[0803] 5 with a compound of the formula , wherein

[0804] R1and R2are independently selected from C-.-e alkyl optionally substituted with one or more R5; C6-10 aryl, optionally substituted with one or more R5, aralkyl

[0805] 10 optionally substituted with one or more R5; cycloalkyl optionally substituted with one or more R5; C 5-10 heteroaryl optionally substituted with one or more R5; and heterocyclylalkyl optionally substituted with one or more R5;

[0806] R3and R4are independently selected from hydrogen, C1-6 alkyl, C8-io aryl, Cs-ioheteroaryl, each optionally substituted with one or more Raand Rb; or R3and

[0807] 15 R4, together with the atoms to which they- are attached form a dihydrophthalazine- 1 ,4-dione: or each R5is independently selected from Ra, Rb, R” substituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb,

[0808] 20 -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb, -O-(CH2)m-C(O)NH-(CH2)m-Rb; each Rais independently selected from the group consisting of hydrogen,

[0809] 25 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10 aryl, C5-10 heteroaryl, Ce-i6 arylalkyd, 2-6 membered heteroalkyl and 3-8 membered

[0810] 93 heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;

[0811] Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Ru, -OR3, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are

[0812] 5 attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;

[0813] Rbis independently selected from the group consisting of =0, -ORd, halogen. Ci-? haloalkyloxy, -OCF3, =S, -SRd, =NRd, =NORd, -NR°R°, -SF5, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NR°R°, -S(O)2NRCR°,

[0814] 10 -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NR°R°, -C(O)Rd, -C(O)ORd, -C(O)NR°RC, -C(NH)NRCR°, -C(NRa)NRcR°, -C(N0H)Ra, -C(NOH)NR°RC, -OC(O)Rd, -OC(O)ORd, -OC(O)NR°R°, -OC(NH)NR°R°, -OC(NRa)NR°R°, -[NHC(O)]„Rd, -[NRaC(O)]„Rd, -[NHC(O)]„ORd, -[NRaC(O)]„ORd, -[NHC(O)]„NRCR°, -[NRaC(O)]KNR°R°,

[0815] 15 -|NHC(NH)]„NRcReand -[NRaC(NRa)]„NR‘>R°; each R° is independently Ra, or, alternatively, two R° are taken together with the nitrogen atom to wInch they’ are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted

[0816] 20 with one or more of the same or different Regroups; each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(O)Rd; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

[0817] 25

[0818] 2. The method of clause 1, wherein the compound has the formula

[0819] 94

[0820]

[0821] 3. The method of clause 1, wherein the compound has the formula

[0822] 5 hod of clause 1, wherein the compound has the formula

[0823] 5. The method of any one of clauses 1 - 4, wherein at least one of R1

[0824] 10 and R2is C6-10 aryl, optionally substituted with one or more R5.

[0825] 6. The method of any one of clauses 1 - 5, wherein R1and R2are both C6-10 and, optionally substituted with one or more R5.

[0826] 15 7. The method of any one of clauses 1 - 6, wherein R1and R2are the same.

[0827] 8. The method of any one of clauses 1 - 5, wherein at least one of R1and R2is C1-6 alkyl.

[0828] 20

[0829] 95 9. The method of any one of clauses 1 - 5, wherein one of R1and R2is aralkyl optionally substituted with one or more R5.

[0830] 10. The method of any one of clauses 1 - 5, wherein one of R1and R2is

[0831] 5 cycloalkyl optionally substituted with one or more R5.

[0832] 11. The method of any one of clauses 1 - 5, wherein one of R1and R2is heteroaryl optionally substituted with one or more R3.

[0833] 10 12. The method of any one of clauses 1 - 5, wherein one of R1and R2is heterocyclylalkyl optionally substituted with one or more R5.

[0834] 13. The method of any one of clauses 1 - 12, wherein at l east one of R3and R4is hydrogen.

[0835] 15

[0836] 14. The method of any one of cl auses 1 - 13, wherein at least one of R3and R4is Cj-6 alkyd.

[0837] 15. The method of any one of clauses 1, 2 and 5 - 12, wherein the

[0838] 20 compound has the formula

[0839] 16. The method of clause 1. wherein the compound has tire formula

[0840] 96

[0841] 5

[0842] 18. The method of clause 1 , wherein the compound has the formula

[0843] 10 19. The method of clause 1, wherein R?is Rathat together with R1and the nitrogen they are both attached to thereto forms a heterocyclylalkyl optionally substituted with one or more Rd.

[0844] 20. The method of clause 1 or clause 19, wherein R4is Rathat together

[0845] 15 with R2and the nitrogen they are both attached to thereto forms a heterocyclylalkyl optionally substituted with one or more Rd.

[0846] 97 21. The method of clause 1. wherein R1and R2independently are selected from

[0847] 98

[0848]

[0849] 5

[0850] 22. The method of any one of clauses 1 - 21, wherein contacting the apyrase comprises treating a crop with the compound.

[0851] 23. The method of clause 22, further comprising treating the crop with a

[0852] 10 pesticide.

[0853] 24. The method of clause 22, wherein the pesticide is selected from acaricides, fungicides, herbicides, insecticides, molluscicides, nematocides, or a combination thereof.

[0854] 15

[0855] 25. The method of clause 23, wherein the pesticide comprises a fungicide.

[0856] 99 26. The method of clause 22, further comprising treating the crop with a fungicide selected from selected from benzimidazoles, dicarboximides, phenylpyrroles, anilinopyrimidines, hydroxyanilides, carboxamides, phenyl amides, phosphonates, cinnamic acids, oxysterol binding protein inhibitors (OSBPI), triazole

[0857] 5 carboxamides, cymoxanil, carbamates, benzamides, demethylation inhibiting piperazines, demethylation inhibiting pyrimidines, demethylation inhibiting azoles, including imidazoles and triazoles, such as cyproconazole, difenoconazole, fenbuconazole, flutriafol, mefentrifluconazole, metconazole, ipconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol,

[0858] 10 triticonazole, morpholines, cyflufenamid, metrafenone, pyriofenone, strobilurins, copper ammonium complex, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, lime sulfur, ethylenebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinam, thiazolidines and combinations thereof.

[0859] 15

[0860] 27. The method of clause 23, wherein the pesticide comprises an herbicide.

[0861] 28. The method of clause 27, wherein the pesticide comprises glyphosate.

[0862] 20

[0863] 29. A composition, comprising a fungicide; compound of the formula

[0864] 25

[0865] 100 wherein R1and R2are independently selected from C1-6 alkyl optionally substituted with one or more Raoptionally substituted with one or more Ra, Rb, or both; C6-10 aryl, optionally substituted with one or more R5, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more

[0866] 5 R5, C 5-10 heteroaryl optionally substituted with one or more R5and heterocyclylalkyl optionally substituted with one or more R5;

[0867] R3and R4are independently selected from hydrogen, C1-6 alkyd, Cs-io aryl, C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they are attached form a dihydrophthal azine-

[0868] 10 1 ,4-dione; or each R3is independently selected from Ra, Rb, Rssubstituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2) m-RD. -(CHRa)w-Rb, -O-(CH2)m-Rb, -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O-

[0869] 15 (CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRn)m-Rb, -O-(CH2),«-C(O)NH-(CH2)m-Rb; each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10 and, C5-10

[0870] 20 heteroaryl, C6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;

[0871] Z is selected from halogen, C1-6 alkyd optionally substituted with one or more Rb, -ORa, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are

[0872] 25 attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;

[0873] Rbis independently selected from the group consisting of =0, -ORd, halogen, C1.3 haloalkyloxy, -OCF3, =S, -SRd, =NRd, =NORd, -NR°R°, -SF5, halogen, -CF3, -CN, -NO'2, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRCRC, -S(O)2NRCRC,

[0874] 101 -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd-OS(O)2NRCR°, -C(O)Rd, -C(O)ORd, -C(O)NR°RC, -C(NH)NR°RC, -C(NRa)NR°Rc, -C(NOH)Ra, -C(NOH)NReR°, -OC(O)Rd, -OC(O)ORd

[0875] -OC(O)NRCR“, -OC(NH)NR°R“, -OC(NRa)NR“R°, -|NHC(O)]„Rd, -[NRaC(O)]„Rd,

[0876] 5 -[NHC(O)]„ORd, -[NRaC(O)]„ORd, -[NHC(O)]„NR°RC, -[NRaC(O)]„NRcRc, -[NHC(NH)]„NR°R° and -[NRaC(NRa)]„NRcRc; each Rcis independently R°, or, alternatively, two R° are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the

[0877] 10 same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different Regroups, each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(O)Rd; each m is independently an integer from 1 to 3; and

[0878] 15 each n is independently an integer from 0 to 3; and a phytologically acceptable carrier.

[0879] 30. The composition of clause 29, wherein the composition comprises from about 1 to about 80 weight percent of the compound.

[0880] 20

[0881] 31. The composition of clause 30, wherein the composition is a suspension formulation.

[0882] 32. The composition of clause 31, wherein the composition comprises

[0883] 25 from about 1 to about 50 weight percent of the compound.

[0884] 33. The composition of clause 32, further comprising sodium polycarboxylate.

[0885] 102 34. The composition of clause 29, further comprising a biocide.

[0886] 35. The composition of clause 30, further comprising organosilicone antifoam emulsion.

[0887] 5

[0888] 36. The composition of clause 33, wherein the composition is a wettable powder.

[0889] 37. The composition of clause 29, wherein the composition is an

[0890] 10 emulsifiable concentrate.

[0891] 38. The composition of clause 37, further comprising tristyrylphenol ethoxylates.

[0892] 15 39. The composition of clause 29, wherein tire composition is an oil dispersible concentrate.

[0893] 40. A pesticidal composition, comprising a pesticide;

[0894] 20 compound of the formula , wherein wherein R1and R2are independently selected from C1-6 alkyl optionally

[0895] 25 substituted with one or more R" optionally substituted with one or more Ra, Rb, or both; C6-10 and, optionally substituted with one or more R5, aralkyl optionally

[0896] 103 substituted with one or more R5, cycloalkyl optionally substituted with one or more R5, C5-10 heteroaryl optionally substituted with one or more R5and heterocyclyl alkyl optionally substituted with one or more R5;

[0897] R3and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl,

[0898] 5 C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they are attached form a dihydrophthalazine- 1 ,4-dione: or each R5is independently selected from Ra, Rb, R3substituted with one or more Ra, Rb, or both and -OR3substituted with one or more of the same or differen t

[0899] 10 Raor Rb, or -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)„,-Rb, -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)w-Rb, -O-(CH2)m-C'(O)NH-(CH2)m-Rb;

[0900] 15 each R8is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky], C3-8 cycloalkyl, C6-10 aryl, C5-10 heteroaiyl, Ce-is arylalkyd, 2-6 membered heteroalkyd and 3-8 membered heterocyclylalkyl, or R8together with the nitrogen and the R1or R2attached thereto forms a heterocyclyl alkyl optionally substituted with one or more Rd;

[0901] 20 Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -OR3, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;

[0902] Rbis independently selected from the group consisting of =0, -ORd, halogen,

[0903] 25 C1-3 haloalkyloxy, -OCF3, =S, -SRd, =NRd, =NORd, -NR°RC, -SFs, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)2Rd-S(O)2ORd, -S(O)NR°R°, -S(O)2NR°RC, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NR°R°, -C(O)Rd, -C(O)ORd, -C(O)NR°R°, -C(NII)NR°RC, -C(NR3)NR°R°, -C(NOH)Ra, -C(NOH)NRCRC, -OC(O)Rd, -OC(O)ORd,

[0904] 104 -OC(O)NRtiR°, -OC(NH)NRtiR°, -OC(NRa)NR°R°, -|NHC(O)]„Rd, -[NRaC(O)]„Rd, -[NHC(O)]„ORd, -[NRaC(O)]„ORd, -[NHC(O)] J4RCRC, -[NRaC(O)]„NRcR°, -[NHC(NH)]„NRCRCand -[NRaC(‘NRa)]„NRcR“; each R° is independently Ra, or, alternatively, two R“ are taken together with

[0905] 5 the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R6groups; each Rdis independently hydrogen or C1-6 alkyl;

[0906] 10 each Reis independently halogen, C1-6 alkyl or -C(O)Rd; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3; and a phytologically acceptable carrier.

[0907] 15 41. The pesticidal composition of clause 40, wherein the pesticide comprises an acaricide, fungicide, herbicide, insecticide, molluscicide, nematocide, or a combination thereof.

[0908] 42. A fungicidal composition, comprising

[0909] 20 a fungicide; compound of the formula , wherein

[0910] 25 wherein R1and R2are independently selected from C1-6 alkyl optionally substituted with one or more R“ optionally substituted with one or more Ra, Rb, or

[0911] 105 both; Cs-io aryl, optionally substituted with one or more R’, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more R5, C5-10 heteroaryl optionally substituted with one or more R5and heterocyclylalkyl optionally substituted with one or more R5;

[0912] 5 R3and R4are independently selected from hydrogen, C1-5 alkyl, C6-10 aryl, C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they are attached form a dihydrophthalazine- 1 ,4-dione: or each R5is independently selected from Ra, Rb, Rasubstituted with one or

[0913] 10 more Ra, Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)m-Rb, -(CHR*%-Rb, -O-(CH2)m-Rb, -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2. -O-(CHR“)m-Rb, -O- (CH2)m-CH[(CH2)wRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb,

[0914] 15 -O-(CH2)m-C(O)NH-(CH2)m-Rb; each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl C2-6 alkynyl, C1-6 haloalkyl, C?-s cycloalkyl, Co-10 aryl, C5-10 heteroaryl, C6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto

[0915] 20 forms a heterocyclylalkyl optionally substituted with one or more Rd;

[0916] Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -ORa, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both:

[0917] 25 Rbis independently selected from the group consisting of =0, -ORd, halogen, C1.3 haloalkyloxy, -OCF3, =S, -SRd, =NRd=NORd, -NR°RC, -SFs, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)?Rd, -S(O)2ORd, -S(O)NR°R°, -S(O)2NR0Rc,

[0918] 106 -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRCR°, -C(O)Rd, -C(O)ORd, -C(O)NR°RC, -C(NH)NR°R°, -C(NRa)NR°Rc, -C(NOH)Ra, -C(NOH)NReR°, -OC(O)Rd, -OC(O)ORd,

[0919] -OC(O)NRCR“, -OC(NH)NR°R“, -OC(NRa)NR“R°, -|NHC(O)]„Rd, -[NRaC(O)]„Rd,

[0920] 5 -[NHC(O)]„ORd, -[NRaC(O)]„ORd, -[NHC(O)]„NR°RC, -[NRaC(O)]„NRcRc, -[NHC(NH)]„NR°R° and -[NRaC(NRa)]„NRcRc; each Rcis independently R°, or, alternatively, two R° are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the

[0921] 10 same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different Regroups, each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(O)Rd; each m is independently an integer from 1 to 3; and

[0922] 15 each n is independently an integer from 0 to 3; and a phytologically acceptable carrier.

[0923] 43. The composition of clause 42, wherein the fungicide is selected from the group consisting of benzimidazoles, dicarboximides, phenylpyrroles,

[0924] 20 anilinopyrimidines, hydroxyanilides, carboxamides, phenyl amides, phosphonates, cinnamic acids, oxysterol binding protein inhibitors, triazole carboxamides, cymoxanil, carbamates, benzamides, demethylation inhibiting piperazines, demethylation inhibiting pyrimidines, demethylation inhibiting azoles, including imidazoles and triazoles, cyproconazole, difenoconazole, fenbuconazole, flutriafol,

[0925] 25 mefentrifluconazole, metconazole, ipconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triti conazole, morpholines, cyflufenamid, metrafenone, pyriofenone, strobilurins, copper ammonium complex, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, lime sulfur,

[0926] 107 ethyl enebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinarn, thiazolidines and combinations thereof.

[0927] In view of the many possible embodiments to which the principles of the

[0928] 5 disclosed invention may be applied, it should be recognized that the illustrated embodi ments are only preferred examples of the invention and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims. We therefore claim as our invention all that comes within the scope and spirit of these claims.

[0929] 108

Claims

We claim:

1. A method for inhibiting apyrase, comprising contacting the apyrase with a compound of the formula, whereinR1and R2are independently selected from C1-6 alkyl optionally substituted with one or more R5; C6-10 aryl, optionally substituted with one or more R5, aralkyl optionally substituted with one or more R5; cycloalkyl optionally substituted with one or more R5; C5-10 heteroaryl optionally substituted with one or more R3: and heterocyclylalkyl optionally substituted with one or more R5;R3and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl, C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they7are attached form a dihydrophthalazine- 1 ,4-dione; or each R5is independently selected from Ra, Rb, Rasubstituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or different R8or Rb, or -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb, -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)„rCH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb, -O-(CH2)m-C(O)NH-(CH2)OT-Rb; each Rais independently7selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10 aryl, C5-10 heieroary 1, C6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered109heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Ru, -OR3, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;Rbis independently selected from the group consisting of =0, -0Rd, halogen. Ci-? haloalkyloxy, -OCF3, =S, -SRd, =NRd, =N0Rd, -NR°R°, -SF5, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NR°R°, -S(O)2NRCR°, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -0S(0)2NR°R°, -C(O)Rd, -C(O)ORd, -C(O)NR°RC, -C(NH)NRCR°, -C(NRa)NRcR°, -C(N0H)Ra, -C(NOH)NR°RC, -OC(O)Rd, -OC(O)ORd, -OC(O)NR°R°, -0C(NH)NR°R°, -0C(NRa)NR°R°, -[NHC(0)]„Rd, -[NRaC(O)]„Rd, -[NHC(0)]„0Rd, -[NRaC(0)]„0Rd, -[NHC(O)]„NRCR°, -[NRaC(0)]KNR°R°, -|NHC(NH)]„NRcReand -[NRaC(NRa)]„NR‘>R°; each R° is independently Ra, or, alternatively, two R° are taken together with the nitrogen atom to wInch they’ are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different Regroups; each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(0)Rd; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3.

2. The method of claim 1 , wherein the compound has the formula1103. The method of claim 1 or claim 2, wherein at least one of R1and R2is C6-10 aryl, optionally substituted with one or more R5; wherein R1and R2are both C6-10 and, optionally substituted with one or more R5; wherein R1and R.2are the same; wherein at least one of R1and R2is C1-6 alkyd; wherein one of R1and R2is aralkyl optionally substituted with one or more R5; wherein one of R1and R2is cycloalkyl optionally substituted with one or more R5; wherein one of R1and R2is heteroaryl optionally substituted with one or more R5; or wherein one of R1and R2is heterocyclylalkyl optionally substituted with one or more R5.

4. The method of any one of claims 1 - 3, wherein at least one of R3and R4is hydrogen.

5. The method of any one of claims 1 - 3, wherein at least one of R3and R4is C1-6 alkyd.

6. The method of claim 1 , wherein the compound has the formula7. The method of claim 1, wherein the compound has a formula selected from:1118. The method of claim 1, wherein R3is Rathat together with R1and the nitrogen they are both attached to thereto forms a heterocyclylalkyl optionally- substituted with one or more Rd.

9. The method of claim 1 or claim 8, wherein R4is Rathat together with R2and the nitrogen they are both attached to thereto forms a heterocyclylalkyl optionally substituted with one or more Rd.

10. The method of claim 1 , wherein R1and R2independently are selected from11211. The method of any one of claims 1 - 10, wherein contacting the apyrase comprises treating a crop with the compound.

12. The method of claim 11, further comprising treating the crop with a pesticide.

13. The method of claim 12, wherein the pesticide is selected from acaricides, fungicides, herbicides, insecticides, molluscicides, nematocides, or a combination thereof.

14. The method of claim 13, wherein the pesticide comprises a fungicide selected from selected from benzimidazoles, dicarboximides, phenylpyrroles, anilinopyrimidines, hydroxyanilides, carboxamides, phenyl amides, phosphonates, cinnamic acids, oxysterol binding protein inhibitors (OSBPI), triazole carboxamides, cymoxanil, carbamates, benzamides, demethylation inhibiting piperazines, demethylation inhibiting pyrimidines, demethylation inhibiting azoles, including imidazoles and triazoles, such as cyproconazole, difenoconazole, fenbuconazole,114flutriafol, mefentrifluconazole, metconazole, ipconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, morpholines, cyflufenamid, metrafenone, pyriofenone, strobilurins, copper ammonium complex, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, lime sulfur, ethylenebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinam, thiazolidines and combinations thereof.

15. A composition, comprising a fungicide; and a compound of the formulawherein R1and R2are independently selected from C1-6 alkyl optionally substituted with one or more Raoptionally substituted with one or more Ra, Rb, or both; C6-10 aryl, optionally substituted with one or more R5, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more R5, C5.10 heteroaryl optionally substituted with one or more R5and heterocyclylalkyl optionally substituted with one or more R5;R?and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl, C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they are attached form a dihydrophthalazine- 1 ,4-dione; or each R5is independently selected from Ra, Rb, R* substituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb,115-S-(CH2),,,-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb,-O-(CH2)m-C(O)NH-(CH2)m-Rb; each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10 aryl, C5-10 heteroaryl, C6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -ORa, C1-6 haloalkyl, or Z, together with R4and tire atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;Rbis independently selected from the group consisting of =0, -0Rd, halogen, Ci-3 haloalkyloxy, -OCF3, ==S, -SRd, ==NRd, =N0Rd, -NR°R°, -SF5, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(0)NR°R°, -S(O)2NRCRC, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd-OS(O)2NRCRC, -C(O)Rd-C(O)ORd, -C(O)NR°RC, -C(NH)NRCR°, -C(NRa)NRcRc, -C(N0H)Ra, -C(N0H)NR°R°, -OC(O)Rd, -0C(0)0Rd, -0C(0)NR°R°, -0C(NH)NR°R°, -0C(NRa)NR°R°, -[NHC(0)]„Rd, -[NRaC(0)]„Rd, -[NHC(0)]„0Rd, -[NRaC(0)]„0Rd-[NHC(O)]„NRCRC, -[NRaC(0)]nNRcRc, -[NHC(NH)]„NRCRCand -[NRaC(NRa)]nNR°Rc; each R° is independently Ra, or, alternatively, two R° are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocy clylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different Regroups; each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(0)Rd;116each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3; and a phytologically acceptable carrier.

16. The composition of claim 15, wherein the composition comprises from about 1 to about 80 weight percent of the compound.

17. A pesticidal composition, comprising a pesticide; compound of the formula wherein R1and R2are independently selected from C1-6 alkyd optionally substituted with one or more Raoptionally substituted with one or more Ra, Rb, or both; C6-10 aryl, optionally substituted with one or more R5, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more R5, C5.10 heteroaryl optionally substituted with one or more R5and heterocyclylalkyl optionally substituted with one or more R5;R?and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl, C5-10 heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they are attached form a dihydrophthalazine- 1 ,4-dione; or each R5is independently selected from Ra, Rb, R* substituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or different Raor Rb, or -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb,117-S-(CH2),,,-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb, ~S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb, -C(O)NH-(CHRa)m-Rb,-O-(CH2)m-C(O)NH-(CH2)m-Rb; each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10 aryl, C5-10 heteroaryl, C6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -ORa, C1-6 haloalkyl, or Z, together with R4and tire atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;Rbis independently selected from the group consisting of =0, -0Rd, halogen, Ci-3 haloalkyloxy, -OCF3, ==S, -SRd, ==NRd, =N0Rd, -NR°R°, -SF5, halogen, -CF3, -CN, -NO2, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(0)NR°R°, -S(O)2NRCRC, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd-OS(O)2NRCRC, -C(O)Rd-C(O)ORd, -C(O)NR°RC, -C(NH)NRCR°, -C(NRa)NRcRc, -C(N0H)Ra, -C(N0H)NR°R°, -OC(O)Rd, -0C(0)0Rd, -0C(0)NR°R°, -0C(NH)NR°R°, -0C(NRa)NR°R°, -[NHC(0)]„Rd, -[NRaC(0)]„Rd, -[NHC(0)]„0Rd, -[NRaC(0)]„0Rd-[NHC(O)]„NRCRC, -[NRaC(0)]nNRcRc, -[NHC(NH)]„NRCRCand -[NRaC(NRa)]nNR°Rc; each R° is independently Ra, or, alternatively, two R° are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocy clylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different Regroups; each Rdis independently hydrogen or C1-6 alkyl; each Reis independently halogen, C1-6 alkyl or -C(0)Rd;118each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3; and a phytologically acceptable carrier.

18. The pesticidal composition of claim 17, wherein the pesticide comprises an acaricide, fungicide, herbicide, insecticide, molluscicide, nematocide, or a combination thereof.

19. A fungicidal composition, comprising a fungicide; compound of tire formula, whereinwherein R1and R2are independently selected from C1-6 alkyl optionally substituted with one or more Raoptionally substituted with one or more Ra, Rb, or both; C6-10 and, optionally substituted with one or more RD, aralkyl optionally substituted with one or more R5, cycloalkyl optionally substituted with one or more R?, C5-10 heteroaryl optionally substituted with one or more R5and heterocyclylalkyl optionally substituted with one or more R5;R3and R4are independently selected from hydrogen, C1-6 alkyl, C6-10 aryl, Ci-jo heteroaryl, each optionally substituted with one or more Raand Rb; or R3and R4, together with the atoms to which they7are attached form a dihydrophthalazine- 1 ,4-dione; or each R5is independently selected from Ra, Rb, R" substituted with one or more Ra, Rb, or both and -ORasubstituted with one or more of the same or differen t119Raor Rb, or -(CH2)„,-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb, -S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb, -O- (CH2)m-CH[(CH2)mRb]Rb-S-(CHRa)m-Rb, -C(O)NH-(CH2)W-Rb, -C(O)NH-(CHRa)m-Rb,-O-(CH2)m-C(O)NFI-(CH2)m-Rb; each Rais independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, Cs-io aryl, C5-10 heteroaryl, Ce-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl, or Ratogether with the nitrogen and the R1or R2attached thereto forms a heterocyclylalkyl optionally substituted with one or more Rd;Z is selected from halogen, C1-6 alkyl optionally substituted with one or more Rb, -ORa, C1-6 haloalkyl, or Z, together with R4and the atoms to which Z and R are attached, forms a 5- or 6-membered ring optionally substituted with one or more of Ra, Rb, and Rasubstituted with one or more Rb, Rd, or both;Rbis independently selected from the group consisting of =0, -0Rd, halogen, C1-3 haloalkyloxy, -OCF3, =S, -SRd, =NRd, =N0Rd, -NR°R°, -SFs, halogen, -CF3, -CN, -N02, -S(O)Rd-S(O)2Rd, -S(O)2ORd, -S(O)NR°RC, -S(O)2NRCRC, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -0S(0)2NR°Rc, -C(O)Rd-C(O)ORd, -C(0)NR°Re, -C(NH)NRCR°, -C(NRa)NRcR°, -C(N0H)Ra, -C(NOH)NRCR°, -OC(O)Rd, -OC(O)ORd, -0C(0)NR°Rc, -0C(NH)NR“R°, -0C(NRa)NR°R°, -[NHC(0)]„Rd, -[NRaC(0)]„Rd, -[NHC(0)]„0Rd, -[NRaC(0)]„0Rd-|NHC(O)]„NRCRC, -[NRaC(0)]nNR°R°, -[NHC(NH)]„NR°R° and -[NRaC(NRa)]„NR°R°; each R° is independently Ra, or. alternatively, two R° are taken together with the nitrogen atom to which they are bonded to form a 5 to 10-membered heterocyclylalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R6groups; each Rdis independently hydrogen or C1-6 alkyl;120each Reis independently halogen, C1-6 alkyd or -C(O)Rd; each m is independently an integer from 1 to 3; and each n is independently an integer from 0 to 3; and a phytologically acceptable carrier.

20. The composition of claim 19, wherein the fungicide is selected from the group consisting of benzimidazoles, dicarboximides, phenylpyrroles, anilinopyrimidines, hydroxyanilides, carboxamides, phenyl amides, phosphonates, cinnamic acids, oxysterol binding protein inhibitors, triazole carboxamides, cymoxanil, carbamates, benzamides, demethylation inhibiting piperazines, demethylation inhibiting pyrimidines, demethylation inhibiting azoles, including imidazoles and triazoles, cyproconazole, difenoconazole, fenbuconazole, flutriafol, mefentrifluconazole, metconazole, ipconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, morpholines, cyflufenamid, metrafenone, pyriofenone, strobil urins, copper ammonium complex, copper hydroxide, copper oxide, copper oxychloride, copper sulfate, sulfur, lime sulfur, ethylenebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinam, thiazolidines and combinations thereof.121

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