Apyrase inhibitors

Abstract

Provided are methods of using molecules as described herein in supporting crop viability and yield, such as by protecting crops from pests. In some cases, the methods inhibit apyrase enzymes by contacting such enzymes with a compound of the formula (I), wherein G, Z, and R1 are as described herein. In further embodiments, an apyrase inhibitor as described herein is used in combination with one or more pesticide to treat a crop at risk of disease.

Description

Attorney Reference: TECS-013 APYRASE INHIBITORS CROSS REFERENCE

[0001] This application claims the benefit of the earlier filing date of U.S. Provisional Application No. 63 / 559,786, filed February 29, 2024, the disclosure of which is incorporated herein by reference. FIELD

[0002] The present disclosure relates to inhibitors of apyrase and methods for their use, in particular in the treatment of crops susceptible to pathogens. INTRODUCTION

[0003] 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. SUMMARY

[0004] Provided are methods of using molecules as described herein in supporting crop viability and yield, such as by protecting crops from pests. In some cases, the methods inhibit apyrase enzymes by contacting such enzymes with a compound of the formula , wherein G, Z, and R1are as described herein.In further embodiments, an apyrase inhibitor as described herein is used in combination with one or more pesticide to treat a crop at risk of disease. DETAILED DESCRIPTION

[0006] Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

[0007] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or interveningAttorney Reference: TECS-013 value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0008] Unless defined 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 invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and exemplary methods and materials may now be described. Any and all publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction.

[0009] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any element, e.g., any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely”, “only” and the like in connection with the recitation of claim elements, or the use of a “negative” limitation.

[0010] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. To the extent the definition or usage of any term herein conflicts with a definition or usage of a term in an application or reference incorporated by reference herein, the instant application shall control.

[0011] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible. DEFINITIONS

[0012] “Administering” refers to any suitable mode of administration, to control a fungal pathogen, including, treatment of an extant crop, seeds, soil or combination thereof.

[0013] “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 toAttorney Reference: TECS-013 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 the crop, pathogen, severity of the pathogen, use restrictions, economic thresholds and other factors known to those of ordinary skill in the art.

[0014] 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 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 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.

[0015] 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 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).

[0016] As used herein, the terms "wettable granule", "water dispersible granule", and "dispersible granule" refer to a solid granular formulation prepared by a granulation process, optionally containing fine particles of polymer-associated active 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 are prepared for application by the 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,Attorney Reference: TECS-013 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.

[0017] As used herein, the terms "wettable powder", "water dispersible powder", and "dispersible powder", refer to a solid powdered 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 powder is prepared for application by the 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.

[0018] 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 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 the 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.

[0019] 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 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 the 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-soluble, water-suspendable or emulsifiable formulations comprising the presently disclosed compounds can also be converted into or formulated as solids (for example, wettable powders), which can then be diluted into a final formulation.Attorney Reference: TECS-013 In 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, flowers or the entire plant.

[0020] Compounds herein can include all stereoisomers, including E and Z isomers, enantiomers, diastereomers, mixtures, racemates, atropisomers, and tautomers thereof.

[0021] Non-limiting examples of optional substituents include hydroxyl groups, sulfhydryl groups, halogens, amino groups, nitro groups, nitroso groups, cyano groups, azido groups, sulfoxide groups, 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, heterocyclylalkyl groups, heteroaryl groups, cycloalkyl groups, acyl groups, acyloxy groups, carbamate groups, amide groups, ureido groups, epoxy groups, and ester groups.

[0022] “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, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, 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 alkyl 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 molecule by a single bond. Whenever it appears herein, a numerical range such as “C1-6alkyl” means that the alkyl group consists of 1 carbon atom, 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 “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 alkyl.

[0023] Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2- methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 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-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, and longer alkyl groups, such as heptyl, octyl, and the like.

[0024] Non-limiting examples of straight alkyl groups include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl.Attorney Reference: TECS-013

[0025] Branched alkyl groups include any straight alkyl group substituted with any number of alkyl groups. Non-limiting examples of branched alkyl groups include isopropyl, isobutyl, sec-butyl, and t- butyl.

[0026] 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, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, the alkyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkyl is optionally substituted with halogen. Non-limiting examples of substituted alkyl groups includes hydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl, 1-chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, and 3- carboxypropyl.

[0027] “Alkenyl” refers to an optionally substituted straight-chain, or optionally substituted branched- 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 C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, C47, C48, C49, or C50 group that is substituted or unsubstituted. Non-limiting examples of alkenyl and alkenylene groups include ethenyl, prop-1-en-1-yl, isopropenyl, but-1-en-4-yl; 2-chloroethenyl, 4- hydroxybuten-1-yl, 7-hydroxy-7-methyloct-4-en-2-yl, and 7-hydroxy-7-methyloct-3,5-dien-2-yl.

[0028] Whenever it appears herein, a numerical range such as “C2-C6alkenyl” 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 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 stated 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 substituted with oxo, halogen, - CN, -CF3, -OH, -OMe, -NH2, 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.

[0029] “Alkynyl” refers to an optionally substituted straight-chain or optionally substituted branched- chain hydrocarbon. The triple bond of an alkynyl group can be internal or terminal. An alkynyl or alkynylene group can be, for example, a C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40,Attorney Reference: TECS-013 C41, C42, C43, C44, C45, C46, C47, C48, C49, or C50group that is substituted or unsubstituted. Non-limiting examples of alkynyl groups include ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, and 2-methyl-hex-4-yn-1-yl; 5-hydroxy-5-methylhex-3-yn-1-yl, 6-hydroxy-6-methylhept-3-yn-2-yl, and 5-hydroxy-5-ethylhept-3-yn- 1-yl.

[0030] Whenever it appears herein, a numerical range such as “C2-C6alkynyl” 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 C2-C8 alkynyl, a C2-C7alkynyl, a C2-C6alkynyl, a C2-C5alkynyl, a C2-C4alkynyl, a C2-C3alkynyl, or a C2alkynyl. 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 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.

[0031] 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 substituted with any number of halogen atoms. A haloalkynyl group can be any alkynyl group substituted with any number of halogen atoms.

[0032] An alkoxy group can be, for example, an oxygen atom substituted with any alkyl, alkenyl, or alkynyl group. An ether or an ether group comprises an alkoxy group. Non-limiting examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, and isobutoxy.

[0033] 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.

[0034] “Alkoxy” refers to a radical of the formula -ORawhere Rais an alkyl radical as defined. Unless 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 optionally substituted with halogen.Attorney Reference: TECS-013

[0035] “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 include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the hydroxyalkyl is aminomethyl.

[0036] “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, tricyclic, 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 aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl. Aryl radicals include, but are not limited to, aryl 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 triphenylene. In some embodiments, the aryl is phenyl. Unless stated otherwise specifically in the specification, an aryl 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 aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, an aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl is optionally substituted with halogen.

[0037] “Cycloalkyl” refers to a stable, partially or fully saturated, monocyclic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom), bridged, or spiro ring systems. Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (C3-C15 cycloalkyl), from three to ten carbon atoms (C3-C10 cycloalkyl), from three to eight carbon atoms (C3-C8 cycloalkyl), 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 cycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl. Non-limiting 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-systems. 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-methyl-cycloprop-1- yl, cycloprop-2-en-1-yl, cyclobutyl, 2,3-dihydroxycyclobut-1-yl, cyclobut-2-en-1-yl, cyclopentyl, cyclopent-2-en-1-yl, cyclopenta-2,4-dien-1-yl, cyclohexyl, cyclohex-2-en-1-yl, cycloheptyl, cyclooctanyl, 2,5-dimethylcyclopent-1-yl, 3,5-dichlorocyclohex-1-yl, 4-hydroxycyclohex-1-yl, 3,3,5-Attorney Reference: TECS-013 trimethylcyclohex-1-yl, octahydropentalenyl, octahydro-1H-indenyl, 3a,4,5,6,7,7a-hexahydro-3H-inden- 4-yl, decahydroazulenyl, bicyclo-[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, 1,3- dimethyl[2.2.1]heptan-2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl.

[0038] Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0039] Polycyclic cycloalkyls or carbocycles include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl.

[0040] Partially saturated cycloalkyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless stated otherwise specifically in the specification, a cycloalkyl 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 cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -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.

[0041] “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, five, or six deuteriums. Deuteroalkyl include, for example, CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. In some embodiments, the deuteroalkyl is CD3.

[0042] “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, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like. In some embodiments, the haloalkyl is trifluoromethyl.

[0043] “Halo” or “halogen” refers to bromo, chloro, fluoro, or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro.

[0044] “Heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g.,

[0045] -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 C1-6heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen,Attorney Reference: TECS-013 nitrogen (e.g. -NH-, -N(alkyl)-), sulfur, or combinations thereof wherein the heteroalkyl is attached to the 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, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heteroalkyl is optionally substituted 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.

[0046] “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyls. 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 hydroxyalkyl is hydroxymethyl.

[0047] A heterocycle can be any ring containing a ring atom that is not carbon, for example, N, O, S, P, Si, B, or any other heteroatom. A heterocycle can be substituted with any number of substituents, for example, alkyl 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.

[0048] “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, imidazolidinyl, oxazolidinyl, isoxazolinyl, thiazolidinyl, isothiazolinyl, oxathiazolidinonyl, oxazolidinonyl, hydantoinyl, tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperazinyl, piperidinyl, dihydropyranyl, tetrahydropyranyl, piperidin-2-onyl, 2,3,4,5-tetrahydro-1H-azepinyl, 2,3-dihydro-1H-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-1H-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- 1H-cycloocta[b]pyrrolyl.

[0049] “Heterocyclylalkyl” or “heterocycloalkyl” or “cycloheteroalkyl” 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 heterocyclylalkyl radical may be a monocyclic,Attorney Reference: TECS-013 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 non-aromatic ring atom) or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocyclylalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized.

[0050] 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-C8heterocyclylalkyl), from two to six carbon atoms (C2-C6 heterocyclylalkyl), from two to five carbon atoms (C2-C5 heterocyclylalkyl), or two to four carbon atoms (C2-C4heterocyclylalkyl). In some embodiments, the heterocyclylalkyl is a 3- to 6-membered heterocyclylalkyl or a 3- to 8-membered heterocyclylalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered heterocyclylalkyl. Examples of such heterocyclylalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-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 (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 optionally substituted with oxo, halogen, methyl, ethyl, -CN, - CF3, -OH, or -OMe. In some embodiments, the heterocyclylalkyl is optionally substituted with halogen.

[0051] “Heteroaryl” 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, bicyclic, tricyclic, or tetracyclic ring system, which 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 nitrogenAttorney Reference: TECS-013 atom may be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, 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-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, 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 heteroaryl is optionally 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. COMPOUNDS

[0052] Provided are apyrase inhibitor compounds. In some cases, the compound has formula (I): wherein:G is monocyclic aryl or monocyclic heteroaryl; wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicyclic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl;Attorney Reference: TECS-013 or Z and R1together with the nitrogen to which they are attached form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl rings optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10 aryl, C6-C10arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, -OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C( NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc, -OC( NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC (O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6 alkyl or C3-8 cycloalkyl; each Reis independently C1-6alkyl, C3-8cycloalkyl, -C(O)Rd, and -C(O)ORd; provided that the compound does not have the formula .

[0053] In some embodiments, G comprises a six-membered aryl or six-membered heteroaryl ring, such as phenyl or pyridine. In some embodiments, G is optionally substituted phenyl, i.e. G can be unsubstituted phenyl or it can be phenyl substituted with Ra, Rb, and Rasubstituted with one or more of the same or different Rb.

[0054] In some cases, G is substituted phenyl. In some cases, G is a phenyl group substituted at its para position, such as with a C1-6alkyl group. In some cases, G is a phenyl group substituted at its para position with a n-propyl group, i.e. G has formula (Ia):Attorney Reference: TECS-013

[0055] In some cases, G is a phenyl para position with an Ar group that is an optionally substituted aryl orin formula (Ib). As such, Ar in formula (Ib) can be an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group, or a substituted heteroaryl group.

[0056] In some embodiments of substituted with an Ragroup of C1-6alkyl, or substituted with an Rbgroup of

[0057] In some cases, G is an optionally substituted biphenyl group, i.e. G is a phenyl group that is substituted with an Ragroup of phenyl. In some cases, the compound has formula (Ib1), i.e. wherein G is an unsubstituted biphenyl group.

[0058] In some cases, G is anIn some cases, the compound has formula (Ic), wherein the sulfonamide is at the 5-position of the pyrimidine ring, and there is an Ar group at the 2-position of the pyrimidine ring, wherein the Ar group of formula (Ic) is optionally substituted aryl or heteroaryl. If “Ar” is aryl, then it will be a C5-C10 aryl, since that is the option for Rarecited in relation to formula (I). If “Ar” is heteroaryl, then it will be a 5-10 membered heteroaryl, since that is the option for Rarecited in relation to formula (I). wherein Ar is optionally substituted aryl

[0059] In some cases, the Ar of formula (Ic) is unsubstituted, substituted with an Ragroup of C1-6alkyl, or substituted with an Rbgroup of halogen.Attorney Reference: TECS-013 Group Z

[0060] As discussed above, Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6alkyl.

[0061] In some cases, Z is substituted phenyl. For instance, Z can be phenyl substituted with an optionally substituted aryl or heteroaryl group. In some cases, Z is phenyl substituted with an optinally substituted alkyl group. In some cases, Z is phenyl substituted with an Rbgroup.

[0062] In some cases, the compound has formula (Id):

[0063] In some cases, the compound :

[0064] In formulas (Id) and (Ie), the Z group is a phenyl group that is substituted with a sulfonamide (- NHSO2-) or (-NHSO2-) group, as allowed for in the description of the options for formula (I).

[0065] In some cases, Z is phenyl substituted with an Rbgroup of halogen or -CF3.

[0066] In some cases, Z is optionally substituted monocyclic heteroaryl, such as pyridyl or pyrimidyl.

[0067] In certain cases, Z and R1together with the nitrogen to which they are attached form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl rings optionally substituted with 1, 2 or 3 groups selected from Raand Rb. In one such embodiment wherein Z and R1together form a 5-, 6-, or 7-membered ring, the ring formed by Z and R1together contains one or more additional heteroatoms. In one aspect of such embodiments, the one or more additional heteroatoms are selected from the group consisting of oxygen, nitrogen and sulfur. In such embodiments wherein an additional heteroatom is nitrogen, the nitrogen atom optionally is substituted. Similarly, in such embodiments wherein an additional heteroatom is sulfur, the sulfur atom optionally is substituted.

[0068] In some cases, Z and R1together with the nitrogen to which they are attached form a fused 5- membered or 6-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb.

[0069] In one embodiment, wherein Z and R1together form a 5-membered or 6-membered ring, the ring formed by Z and R1together contains one or more additional heteroatoms. In one such embodiment, the ring formed by Z and R1together is a morpholinyl or piperazinyl ring.Attorney Reference: TECS-013

[0070] In one embodiment, wherein Z and R1together form a 5-membered or 6-membered ring, the ring formed by Z and R1together is fused to an aromatic or heteroaromatic ring, which may be substituted or unsubstituted. In one such embodiment wherein Z and R1together form a 5-membered or 6-membered ring, the ring formed by Z and R1together is fused to an aromatic or heteroaromatic ring, which is substituted with 1, 2 or 3 groups selected from Raand Rb. In one embodiment wherein a ring formed by Z and R1together is fused to an aromatic or heteroaromatic ring, the resulting fused ring system is an indoline ring system.

[0071] In some embodiments, Z is selected from the group consisting of: O N ,

[0072] In some cases, features of the G groups can be combined with features of the Z groups. For instance, in some cases the G group shown in formulas (Ia), (Ib), (Ib1), or (Ic) can be combined with the Z group shown in formulas (Id) or (Ie) in any possible combination. Additional aspects

[0073] As discussed above, each Rdis independently C1-6alkyl or C3-8cycloalkyl. In some cases, Rdis C1-3 alkyl or C3-4 cycloalkyl.

[0074] As discussed above, each Reis independently C1-6alkyl or C3-8cycloalkyl. In some cases, Reis C1-3 alkyl or C3-4 cycloalkyl.

[0075] As discussed above, many groups can be substituted with Raor Rb. Additionally, Racan be substituted with Rb. In some cases, Rbis a group that includes an Rcgroup, which can be Ra. In some cases, Rbis a group that includes a Rdgroup, which is Ra. There can be a limit on the number of times that a substituted is substituted with another substituent. For example, in some cases Rais not substituted with Rb.Attorney Reference: TECS-013

[0076] In some cases, the size of a group can be limited by specifying the number of non-hydrogen atoms in the group. For example, in some cases Z and its substituents have 6 to 20 non-hydrogen atoms, such as 6 to 16 non-hydrogen atoms or 6 to 12 non-hydrogen atoms. These numbers of non-hydrogen atoms include all levels of substitution. For example, in Compound A-1 shown below in the next section, Z can be interpreted as a phenyl (6 atoms) substituted with an Raof methyl (1 atom) and Raof tetrazole (5 atoms), wherein the tetrazole is further substituted with Rbof methyl (1 atom), thereby giving a total non- hydrogen atom could of 6+1+5+1 or 13 atoms. Thus, the methyl on the tetrazole is a second-level substitution of the original Z group of phenyl, but this methyl on tetrazole is still counted towards the number of non-hydrogen atoms for Z.

[0077] Similarly, in some cases the G group can have a certain number of non-hydrogen atoms, such as 6 to 20 non-hydrogen atoms, 6 to 16 non-hydrogen atoms, or 6 to 12 non-hydrogen atoms. In Compound A-1 of the next section, G is a phenyl group (6 atoms) substituted with an Ragroup of methyl (3 atoms) for a total of 9 non-hydrogen atoms in G. Specific Embodiments of Compounds

[0078] In some cases, the compound has a structure selected from Table 1, which is shown below. Table 1 - eAttorney Reference: TECS-013 N-(2,5-dimethylphenyl)-[1,1'- - - m-Attorney Reference: TECS-013 N-(4H-1,2,4-triazol-3-yl)- e - hAttorney Reference: TECS-013 N-(2-(3-methyl-4H-1,2,4- 4- 4- eAttorney Reference: TECS-013 N-(3-(1-cyclopropyl-1H- - h id e hAttorney Reference: TECS-013 N-(benzo[d][1,3]dioxol-5- h 4- h hAttorney Reference: TECS-013 e e e e hAttorney Reference: TECS-013 e 4- eAttorney Reference: TECS-013 N-(2,3- dihydrobenzo[b][1,4]dioxin- - e li lAttorney Reference: TECS-013 4-cyclohexyl-N-(m- H-Attorney Reference: TECS-013 N-(2-chlorophenyl)-4- A-71 f ze e - h eAttorney Reference: TECS-013 N-cyclohexyl-N-methyl-4- ((4- e e e )- e e - es eAttorney Reference: TECS-013 e d hAttorney Reference: TECS-013 4- e e '- - ti e aAttorney Reference: TECS-013 N-(4-methyl-3- A-104 sulfamoylphenyl)-4-Attorney Reference: TECS-013 e h hAttorney Reference: TECS-013 N-(5-chloro-2-(1H-1,2,4- eTARGET CROPS AND THEIR PATHOGENS

[0079] The present disclosure provides formulations and methods for their use in treating crops for pathogens. In one embodiment, a disclosed compound 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 ordinary skill 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.

[0080] Roux and coworkers describe the compounds:different plant-pathogenic fungi. These compounds are referred to herein as “Roux compound 1,” and “Roux compound 13,” respectively (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 than Roux compounds 1 and 13.Attorney Reference: TECS-013

[0081] 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 applied to improved varieties / varieties, cultivars, as well as mutants, hybrids and genetically modified embodiments of these plants.

[0082] 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. occurring in agricultural or horticultural crops, including flowers, lawns, and pastures.

[0083] 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.

[0084] The present compounds are useful for potentiating the effects of herbicides. For example, the present compounds can be used in combination with one or more herbicide to control weeds or other unwanted vegetation.

[0085] 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.

[0086] The present compounds are useful for potentiating the effects of acaricides or miticides. For example, the present compounds can be used in combination with one or more acaricidal agent to control mites.

[0087] The present compounds are useful for potentiating the effects of molluscicides. For example, the present compounds can be used in combination with one or more molluscicide to prevent interference of slugs or snails with a crop.

[0088] 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 nematodes with a crop.

[0089] 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, Colletotrichum graminicola, Fusarium oxysporum, Sclerotiana sclerotiorum, Verticillium dahlia, Mycospharella gramincola and Sphacelotheca reliana.

[0090] 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 ofAttorney Reference: TECS-013 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.

[0091] The genus Colletotrichum 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).

[0092] Fusarium wilt of banana, caused by the soil-borne fungus Fusarium oxysporum f.sp. cubense, is a 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).

[0093] The white mold fungus Sclerotinia sclerotiorum is known to attack more than 400 host species and is considered one of the most prolific plant pathogens. The majority of the affected crop species are dicotyledonous, along with a number of agriculturally significant monocotyledonous plants. Some important crops affected by S. sclerotiorum include legumes (soybean), most vegetables, stone fruits and tobacco.

[0094] The ascomycete Verticillium dahliae is a soil-borne 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 and ornamental plants.

[0095] 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 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.

[0096] The basidiomycete fungus Sphacelotheca reliana infects corn (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 converted to sori containing masses of powdery teliospores that resemble mature galls of common smut.

[0097] Examples of crops to be treated and plant diseases (pathogens) to be controlled using the presently disclosed compounds and compositions include, without limitation: Sugar beet: brown spot disease (Cercospora beticola), black root disease (Aphanomyces cochlioides), root rot disease (Thanatephorus cucumeris), leaf rot disease (Thanatephorus cucumeris), and the like.

[0098] Peanut: brown spot disease (Mycosphaerella arachidis), leaf mold (Ascochyta sp.), rust disease (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.Attorney Reference: TECS-013

[0099] Cucumber: powdery mildew (Sphaerotheca fuliginea), downy mildew (Pseudoperonospora cubensis), gummy stem blight (Mycosphaerella melonis), wilt disease (Fusarium oxysporum), sclerotinia rot (Sclerotinia sclerotiorum), gray mold (Botrytis cinerea), anthracnose (Colletotrichum orbiculare), scab (Cladosporium cucumerinum), brown spot disease (Corynespora cassiicola), damping-off disease (Pythium debaryanum, Rhizoctonia solani Kuhn), Phomopsis root rot disease (Phomopsis sp.), Bacterial spot (Pseudomonas syringae pv. Lechrymans), and the like.

[0100] Tomato: gray mold disease (Botrytis cinerea), 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 mold disease (Pseudocercospora fuligena), and the like.

[0101] Eggplant: gray mold disease (Botrytis cinerea), 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. 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. Onion: neck rot disease (Botrytis allii), gray mold disease (Botrytis cinerea), leaf blight disease (Botrytis squamosa), downy mildew disease (Peronospora destructor), Phytophthora porn disease (Phytophthora porn), and the like.

[0102] 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 mildew disease (Peronospora parasitica), sclerotinia rot disease (Sclerotinia sclerotiorum), black spot disease (Alternaria brassicicola), gray mold disease (Botrytis cinerea), and the like.

[0103] Common bean: sclerotinia rot disease (Sclerotinia sclerotiorum), gray mold disease (Botrytis cinerea), anthracnose (Colletotrichum lindemuthianum), angular spot disease (Phaeoisariopsis griseola), and the like.

[0104] Apple: powdery mildew disease (Podosphaera leucotricha), scab disease (Venturia inaequalis), Monilinia disease (Monilinia mali), black spot disease (Mycosphaerella pomi), valla canker disease (Valsa mali), alternaria blotch disease (Alternaria mali), 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), Sooty blotchAttorney Reference: TECS-013 (Gloeodes pomigena), violet root rot disease (Helicobasidium mompa), gray mold disease (Botrytis cinerea), and the like.

[0105] Japanese apricot: scab disease (Cladosporium carpophilum), gray mold disease (Botrytis cinerea), brown rot disease (Monilinia mumecola), and the like.

[0106] Persimmon: powdery mildew disease (Phyllactinia kakicola), anthracnose disease (Gloeosporium kaki), angular leaf spot (Cercospora kaki), and the like.

[0107] 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.

[0108] Almond: brown rot disease (Monilinia taxa), spot blotch disease (Stigmina carpophila), scab disease (Cladosporium carpophilum), red leaf spot disease (Polystigma rubrum), alternaria blotch disease (Alternaria alternata), anthracnose (Colletotrichum gloeospoides), and the like.

[0109] Yellow peach: brown rot disease (Monilinia fructicola), anthracnose disease (Colletotrichum acutatum), black spot disease (Alternaria sp.), Monilinia kusanoi disease (Monilinia kusanoi), and the like.

[0110] Grape: gray mold disease (Botrytis cinerea), powdery mildew disease (Uncinula necator), ripe rot disease (Glomerella cingulata, Colletotrichum acutatum), downy mildew disease (Plasmopara viticola), anthracnose disease (Elsinoe ampelina), brown spot disease (Pseudocercospora vitis), black rot disease (Guignardia bidwellii), white rot disease (Coniella castaneicola), rust disease (Phakopsora ampelopsidis), and the like.

[0111] Pear: scab disease (Venturia nashicola), rust disease (Gymnosporangium asiaticum), black spot disease (Alternaria kikuchiana), ring rot disease (Botryosphaeria berengeriana), powdery mildew disease (Phyllactinia mali), Cytospora canker disease (Phomopsis fukushii), brown spot blotch disease (Stemphylium vesicarium), anthracnose disease (Glomerella cingulata), and the like.

[0112] Tea: ring spot disease (Pestalotiopsis longiseta, P. theae), anthracnose disease (Colletotrichum theae-sinensis), Net blister blight (Exobasidium reticulatum), and the like.

[0113] 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 sp.), and the like.

[0114] Wheat: powdery mildew (Blumeria graminis f. 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 (Septoria tritici), glume blotch disease (Leptosphaeria nodorum), typhula snow blight disease (Typhula incarnata), sclerotinia snow blight disease (Myriosclerotinia borealis), damping-off diseaseAttorney Reference: TECS-013 (Gaeumannomyces graminis), ergot disease (Claviceps purpurea), stinking smut disease (Tilletia caries), loose smut disease (Ustilago nuda), and the like.

[0115] Barley: leaf spot disease (Pyrenophora graminea), net blotch disease (Pyrenophora teres), leaf blotch disease (Rhynchosporium secalis), loose smut disease (Ustilago tritici, U. nuda), and the like.

[0116] Rice: blast disease (Pyricularia oryzae), sheath blight disease (Rhizoctonia solani), bakanae disease (Gibberella fujikuroi), 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 (Burkholderia glumae), Cercospora leaf spot disease (Cercospora oryzae), false smut disease (Ustilaginoidea virens), rice brown spot disease (Alternaria alternata, Curvularia intermedia), kernel discoloration of rice (Alternaria padwickii), pink coloring of rice grains (Epicoccum purpurascens), and the like.

[0117] Tobacco: sclerotinia rot disease (Sclerotinia sclerotiorum), powdery mildew disease (Erysiphe cichoracearum), phytophthora rot disease (Phytophthora nicotianae), and the like.

[0118] Tulip: gray mold disease (Botrytis cinerea), and the like.

[0119] Sunflower: downy mildew disease (Plasmopara halstedii), sclerotinia rot disease (Sclerotinia sclerotiorum), and the like.

[0120] Bent grass: Sclerotinia snow blight (Sclerotinia borealis), Large patch (Rhizoctonia solani), Brown patch (Rhizoctonia solani), Dollar spot (Sclerotinia homoeocarpa), blast disease (Pyricularia sp.), Pythium red blight disease (Pythium aphanidermatum), anthracnose disease (Colletotrichum graminicola), and the like.

[0121] Orchard grass: powdery mildew disease (Erysiphe graminis), and the like.

[0122] Soybean: purple stain disease (Cercospora kikuchii), downy mildew disease (Peronospora 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.

[0123] Potato: hytophthora rot disease (Phytophthora infestans), early blight disease (Alternaria solani), scurf disease (Thanatephorus cucumeris), verticillium wilt disease (Verticillium albo-atrum, V. dahlia, V. nigrescens, and the like.

[0124] Banana: Panama disease (Fusarium oxysporum), Sigatoka disease (Mycosphaerella fijiensis, M. musicola), and the like.

[0125] Rapeseed: sclerotinia rot disease (Sclerotinia sclerotiorum), root rot disease (Phoma lingam), black leaf spot disease (Alternaria brassicae), and the like.Attorney Reference: TECS-013

[0126] Coffee: rust disease (Hemileia vastatrix), anthracnose (Colletotrichum coffeanum), leaf spot disease (Cercospora coffeicola), and the like.

[0127] Sugarcane: brown rust disease (Puccinia melanocephala), and the like.

[0128] Corn: zonate spot disease (Gloeocercospora sorghi), rust disease (Puccinia sorghi), southern rust disease (Puccinia polysora), smut disease (Ustilago maydis), brown spot disease (Cochliobolus heterostrophus), northern leaf blight (Setosphaeria turcica), and the like.

[0129] Cotton: seedling blight disease (Pythium sp.), rust disease (Phakopsora gossypii), sour rot disease (Mycosphaerella areola), anthracnose (Glomerella gossypii), and the like. PESTICIDES

[0130] The presently disclosed compounds are useful for enhancing the effect of a variety of agrochemicals, including fungicides, antiviral agents, bactericides, herbicides, insecticidal / acaricidal agents, molluscicides, nematicides, soil pesticides, plant control agents, synergistic agents, fertilizers and soil conditioners.

[0131] 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 are well known to those of skill in the art and include, without limitation, those set forth by class in Table 2, which is shown below. Table 2 , -Attorney Reference: TECS-013 Table 2 Trade Names n, ar,Attorney Reference: TECS-013 Table 2 Family & Group # Common Names Trade Names (Combination Products) o, e , z, dAttorney Reference: TECS-013 Table 2 Trade Names ) ,Attorney Reference: TECS-013 Table 2 Family & Group # Common Names Trade Names (Combination Products) y e m e, t, il,Attorney Reference: TECS-013 Table 2 Family & Group # Common Names Trade Names (Combination Products)

[0132] 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 entirety.

[0133] In one embodiment, a presently disclosed enhancer compound is used in combination 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.

[0134] In particular embodiments, a disclosed enhancer is used in combination with one or more of a 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, 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, ethylenebisdithiocarbamates, aromatic hydrocarbons, phthalimides, guanidines, polyoxins, fluazinam and thiazolidines.

[0135] 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, triticonazole, and prothioconazole.

[0136] In one embodiment, the combined treatment with a selected fungicide and an enhancer according to the present disclosure provides synergistic fungicidal activity against plant pathogenic fungi.

[0137] In one embodiment, the disclosure provides compositions and methods of treating plants or plant 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 combinationAttorney Reference: TECS-013 with other compounds in addition to the presently disclosed apyrase inhibitors. As with the apyrase 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 crop growth.

[0138] In one embodiment, the presently disclosed compounds 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 way of example, suitable herbicides for 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 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 solanesyltransferase inhibitors, lycopene cyclase inhibitors.

[0139] In one embodiment, the presently disclosed compounds 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. FORMULATIONS Formulations

[0140] The present disclosure provides specific apyrase inhibitors to enhance the 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 from about 25% to about 55%, such 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% weight 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, 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 theAttorney Reference: TECS-013 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.

[0141] The enhancer, pesticide and combinations thereof are not particularly limited by the dosage form. Examples of the dosage form include wettable powders, emulsions, emulsifiable concentrates, oil- dispersible liquids, powders, granules, water-soluble agents, suspensions, granular wettable powders, and tablets. The method for preparing formulation is not particularly limited, and conventionally-known methods may be adopted depending on the dosage form.

[0142] Several formulation examples are described below. The preparation formulations shown below 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 below.

[0143] "Part" means "part by mass" unless otherwise specified.

[0144] Formulation Example 1: Wettable Powders

[0145] 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 alkyl naphthalene sulfonate are mixed uniformly, and then finely pulverized to obtain wettable powders containing 40 parts by mass of the enhancer.

[0146] Formulation Example 2: Emulsifiable Concentrates

[0147] 3 parts of an enhancer disclosed herein, 60 parts of mixed petroleum distillates, 27 parts of dimethyl lactamide, and 10 parts of tristyrylphenol ethoxylates are mixed and dissolved to obtain an emulsifiable concentrate containing 3% by mass of the enhancer.

[0148] Formulation Example 3: Granules

[0149] 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 disclosed herein are obtained.

[0150] Formulation Example 4: Granules

[0151] 5 parts of an enhancer disclosed herein, 73 parts of clay, 20 parts of bentonite, 1 part of sodium dioctyl 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.

[0152] Formulation Example 5: Suspensions

[0153] 10 parts of an enhancer disclosed herein, 4 parts of polyoxyethylene alkyl ether, 2 parts of 3 kDa sodium polycarboxylate as dispersant, 10 parts of glycerin, 0.2 parts of xanthan gum, 0.1 parts of biocidesAttorney Reference: TECS-013 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 the enhancer.

[0154] Formulation Example 6: Oil Dispersible Concentrates

[0155] 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.

[0156] The skilled artisan will recognize that the various compositions are used commercially at varying 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. METHODS FOR ASSESSING ENHANCED ACTIVITY Apyrase inhibition assay

[0157] 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

[0158] Screen for Apyrase Inhibitors –

[0159] 96 well plates were used for the assay: (Greiner bio-one: REF- 655901- 96 well, PS, F-bottom, Clear, Non-binding)

[0160] Buffers:

[0161] Reaction Buffer: 60mM Hepes; 3mM MgCl2, 3mM CaCl2 and 3mM ATP (pH 6.5)

[0162] Development Buffer A: 2% aqueous ammonium molybdate

[0163] Development Buffer B: 11% ascorbic acid in 37.5% TCA in water

[0164] Stop buffer C: 2% trisodium citrate in 2% acetic acid solution in water

[0165] Steps:

[0166] Add 100 µl of reaction buffer to each well.

[0167] Add 10µl of DMSO (control) or inhibitor / compound or compounds such as N1915 or orthovanadate to each well. (use inhibitor conc at 1mM; orthovanadate at 2mM and N1915 at 1mM)

[0168] Add 10µl of apyrase (concentration based on optimization – Dilute 1U / µl enzyme to different concentrations such as 0.1U, 0.05U, 0.0025, 0.001U, 0.0005U- to find a good range)

[0169] Incubate plate at room temperature for 1hr

[0170] Mix development buffer A and B in the ratio of 1:1.5 (just before use).Attorney Reference: TECS-013

[0171] Add 50ul of A:B mix in each well (incubate for 2 mins)

[0172] Add 50ul of C in each well

[0173] Measure / Read Absorbance of plate @630nm

[0174] Inhibitory data for the apyrase assay described above are provided for selected compounds in Table 3. D is inhibition of 0% to 10%, C is inhibition from 10% to 20%, B is inhibition from 20% to 30%, and A is inhibition above 30%. Blank entries signify compounds that were not tested. Table 3 Compound InhibitionAttorney Reference: TECS-013 A-27 D A-28 DAttorney Reference: TECS-013 A-60 D A-61 DAttorney Reference: TECS-013 A-93 D A-94 AMethod 2: In vitro Assessment of Combination Activity

[0175] Selected compounds are assessed in combination with fungicides against a range of commercially important plant pathogenic fungi.

[0176] 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 the test compound. The test compounds are recorded as active if control of the pathogen was observed.Attorney Reference: TECS-013

[0177] 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 gave 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 the test compound is added at Rate 2, where Rate 2 is higher than Rate 1. Finally, as a benchmark, Well 4 is the same as Well 1, except that it contained the fungicide at a higher rate, at which it gave 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 compounds are scored as inactive, active or highly active.

[0178] 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, Microdochium nivale. In this assay, Roux Compound 13 exhibited 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, compounds of the present disclosure are effective in the combination assay, enhancing fungicidal activity of one or more fungicides against at least one strain. Method 3: Greenhouse Crop Tests

[0179] 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, wheat plants (JB Diego) were used. Seeds were sown in 9cm diameter pots to a depth of 1 to 2 cm using Petersfield potting compost (75% medium 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 11 growth stage (first pair of true leaves (unifoliate) unfolded). Wheat plants were inoculated with Puccinia triticina (Brown rust) 24 hours after 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 replicates were used for each combination of fungicide, pathogen and test compound. Each plant was evaluated at fourteen days (once the disease symptoms were fully expressed) for % control of the disease. Appropriate controls were used for all experiments, including an ‘inoculationAttorney Reference: TECS-013 check’ wherein plants were inoculated with their specific pathogen to assess 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. Exemplary compounds 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, enhance the activity of fungicides, thus the enhancer compounds work synergistically in combination with fungicides to control disease.

[0180] Amistar (0.04 L / ha)

[0181] Imtrex (0.45 L / ha)

[0182] Proline (0.15 L / ha)

[0183] Balaya (0.25 L / ha) Table 4 C m nd Ami t r Imtr x Pr lin B l aMethod 4: Enhancement of Herbicide Activity

[0184] This method demonstrates the enhancement of herbicidal activity provided by the present compounds. Specifically, Amaranthus retroflexus (pigweed) was treated pre-emergence with metribuzinAttorney Reference: TECS-013 alone or in combination with 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 rate shown in Table 5 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 5. Exemplary compounds A-62, A-8, A-29, A-3, A-108, A-34, A-21, A-59 and A-103 demonstrated significant enhancement of metribuzin herbicidal activity at seven and fourteen days.Attorney Reference: TECS-013 Table 5. Pre-Emergence Amaranthus Kill Percentage Assessed 7 DAT Assessed 14 DAT Enhancer Metribuzin rate (g / ha) Metribuzin rate (g / ha)METHODS OFMAKINGENHANCERCOMPOUNDS

[0185] Exemplary enhancer compounds were purchased from commercial suppliers, such as Enamine, located at Industriepark Hoechst, G837. 65926 Frankfurt am Main Germany. Other compounds were prepared consistent with the methods set forth below: Synthesis of compounds

[0186] Compounds of the present disclosure can be synthesized according to the scheme shown below. Specifically, an aryl sulfonyl chloride can be allowed to react with the amine NHR1R2to give the requiredAttorney Reference: TECS-013 sulfonamide. The R group on the aryl ring can have various forms and variations. In some cases, the aryl ring can be substituted with an R group at the ortho or meta position, or substituted with multiple R groups at multiple positions.

[0187] wherein:

[0188] n and m than or equal to 3.

[0189] Raand Rbare as described herein. In some cases Rais phenyl, alkyl, heteroaryl, or cycloalkyl.

[0190] Such syntheses are reported in Journal of Medicinal Chemistry 2022, 65, 15710-15724; Bioorganic & Medicinal Chemistry Letters 2020, 30, 127650; and Journal of Medicinal Chemistry 2004, 47, 4979-4982.

[0191] Many sulfonyl chloride (-SO2Cl) starting compounds that can be used in the above scheme are commercially available, or can be chemically synthesized from commercially available compounds. For example, the compound 4-biphenylsulfonyl chloride (CAS number 1623-93-4) is an exemplary starting material where m is 0, n is 1, and the one Ragroup is phenyl. 4-biphenylsulfonyl chloride is commercially sold by more than 60 chemical suppliers. APPENDIX 1

[0192] Shown below is Appendix 1 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODEAttorney Reference: TECS-013 A4 Bactericide. Resistance known. carb Risk in fungi unknown. DNA topoisomerase oxylic acids carboxylic acids oxolinic acid Resistance management 31 II 2Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL ORCOMMON NAME COMMENTSFRACAND CODE BIOLOGICAL GROUP CODE Resistance common in manAttorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE 9Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE zx trbin 1 AAttorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE R itn rik nknwn bt 1 9 0 8 5 3 4 5Attorney Reference: TECS-013 D5 Bactericide. Resistance protein synthesis tetracycline known. High risk. tetracyc (ribosome, antibiotic line antibiotic oxytetracycline Resistance management 41CAND CODE BIOLOGICAL GROUP CODE 3 2Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE 8 8 9 1Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODEAttorney Reference: TECS-013 oxidase (S 18 squalene-ep BI class IV) allylamines naftifine Medical fungicides only. in sterol terbinafineAttorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE 6 9 0 1 2 .3Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE 1 2 3 4 5 6 7 8Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE 7 4 5 6 7 6 2 3 4 6 7 8Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC AND CODE BIOLOGICAL GROUP CODE C 01 02 03 04 05 06 07 08 09 10 11 12Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAMECHEMICAL ORCOMMON NAME COMMENTSFRACBIOLOGICAL GROUP CODE 01Attorney Reference: TECS-013 MOA TARGET SITE GROUP NAME CHEMICAL OR COMMON NAME COMMENTS FRAC BIOLOGICAL GROUP CODE 02Attorney Reference: TECS-013 APPENDIX 2

[0193] Shown below is Appendix 2. MODE OF ACTION CHEMICAL CLASSIFICATION ACTIVE Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Alloxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Butroxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Clethodim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Cloproxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Cycloxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Profoxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Sethoxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Tepraloxydim Inhibition of Acetyl CoA Carboxylase Cyclohexanediones (DIMs) Tralkoxydim Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Clodinafop-propargyl Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Clofop Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Cyhalofop-butyl Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Diclofop-methyl Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Fenoxaprop-ethyl Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Fenthiaprop Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Fluazifop-butyl Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Haloxyfop-methyl Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Isoxapyrifop Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Metamifop Inhibition of Acetyl CoA Aryloxyphenoxy-propionates Carboxylase (FOPs) Quizalofop-ethyl Inhibition of Acetyl CoA Carboxylase Phenylpyrazoline Pinoxaden Inhibition of Acetolactate Synthase Pyrimidinyl benzoates Bispyribac-sodium Inhibition of Acetolactate Pyribenzoxim (prodrug of Synthase Pyrimidinyl benzoates bispyribac)Attorney Reference: TECS-013 Inhibition of Acetolactate Synthase Pyrimidinyl benzoates Pyriftalid Inhibition of Acetolactate Synthase Pyrimidinyl benzoates Pyriminobac-methyl Inhibition of Acetolactate Synthase Pyrimidinyl benzoates Pyrithiobac-sodium Inhibition of Acetolactate Synthase Sulfonanilides Pyrimisulfan Inhibition of Acetolactate Synthase Sulfonanilides Triafamone Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 1 Cloransulam-methyl Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 1 Diclosulam Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 1 Florasulam Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 1 Flumetsulam Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 1 Metosulam Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 2 Penoxsulam Inhibition of Acetolactate Synthase Triazolopyrimidine - Type 2 Pyroxsulam Inhibition of Acetolactate Synthase Sulfonylureas Amidosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Azimsulfuron Inhibition of Acetolactate Synthase Sulfonylureas Bensulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Chlorimuron-ethyl Inhibition of Acetolactate Synthase Sulfonylureas Chlorsulfuron Inhibition of Acetolactate Synthase Sulfonylureas Cinosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Cyclosulfamuron Inhibition of Acetolactate Synthase Sulfonylureas Ethametsulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Ethoxysulfuron Inhibition of Acetolactate Synthase Sulfonylureas Flazasulfuron Inhibition of Acetolactate Synthase Sulfonylureas Flucetosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Flupyrsulfuron-methyl-Na Inhibition of Acetolactate Synthase Sulfonylureas ForamsulfuronAttorney Reference: TECS-013 Inhibition of Acetolactate Synthase Sulfonylureas Halosulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Imazosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Iodosulfuron-methyl-Na Inhibition of Acetolactate Synthase Sulfonylureas Mesosulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Metazosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Metsulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Nicosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Orthosulfamuron Inhibition of Acetolactate Synthase Sulfonylureas Oxasulfuron Inhibition of Acetolactate Synthase Sulfonylureas Primisulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Propyrisulfuron Inhibition of Acetolactate Synthase Sulfonylureas Prosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Pyrazosulfuron-ethyl Inhibition of Acetolactate Synthase Sulfonylureas Rimsulfuron Inhibition of Acetolactate Synthase Sulfonylureas Sulfometuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Sulfosulfuron Inhibition of Acetolactate Synthase Sulfonylureas Triasulfuron Inhibition of Acetolactate Synthase Sulfonylureas Tribenuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Thifensulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Trifloxysulfuron-Na Inhibition of Acetolactate Synthase Sulfonylureas Triflusulfuron-methyl Inhibition of Acetolactate Synthase Sulfonylureas Tritosulfuron Inhibition of Acetolactate Synthase Imidazolinones Imazamethabenz-methyl Inhibition of Acetolactate Synthase Imidazolinones Imazamox Inhibition of Acetolactate Synthase Imidazolinones Imazapic Inhibition of Acetolactate Synthase Imidazolinones Imazapyr Inhibition of Acetolactate Synthase Imidazolinones ImazaquinAttorney Reference: TECS-013 Inhibition of Acetolactate Synthase Imidazolinones Imazethapyr Inhibition of Acetolactate Synthase Triazolinones Flucarbazone-Na Inhibition of Acetolactate Synthase Triazolinones Propoxycarbazone-Na Inhibition of Acetolactate Synthase Triazolinones Thiencarbazone-methyl Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Atraton Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Atrazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Ametryne Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Aziprotryne=aziprotryn Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Chlorazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines CP 17029 Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Cyanazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Cyprazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Desmetryne Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Dimethametryn Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Dipropetryn Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Eglinazine-ethyl Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Ipazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Methoprotryne=methoprotryn Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines procyazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Proglinazine-ethyl Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Prometon Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Prometryne Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Propazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Sebuthylazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Secbumeton Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines SimetryneAttorney Reference: TECS-013 Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Simazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Terbumeton Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Terbuthylazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Terbutryne Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazines Trietazine Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazolinone Amicarbazone Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazinones Ethiozin Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazinones Hexazinone Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazinones Isomethiozin Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazinones Metamitron Inhbition of Photosynthesis at PSll - Serine 264 Binders Triazinones Metribuzin Inhbition of Photosynthesis at PSll - Serine 264 Binders Uracils Bromacil Inhbition of Photosynthesis at PSll - Serine 264 Binders Uracils Isocil Inhbition of Photosynthesis at PSll - Serine 264 Binders Uracils Lenacil Inhbition of Photosynthesis at PSll - Serine 264 Binders Uracils Terbacil Inhbition of Photosynthesis at PSll - Serine 264 Binders Phenlcarbamates Chlorprocarb Inhbition of Photosynthesis at PSll - Serine 264 Binders Phenlcarbamates Desmedipham Inhbition of Photosynthesis at PSll - Serine 264 Binders Phenlcarbamates Phenisopham Inhbition of Photosynthesis at PSll - Serine 264 Binders Phenlcarbamates Phenmedipham Inhbition of Photosynthesis at PSll - Serine 264 Binders Pyridazinone Chloridazon (=pyrazon) Inhbition of Photosynthesis at PSll - Serine 264 Binders Pyridazinone Brompyrazon Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Benzthiazuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Bromuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas ButuronAttorney Reference: TECS-013 Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Chlorbromuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Chlorotoluron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Chloroxuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Difenoxuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Dimefuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Diuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Ethidimuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Fenuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Fluometuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Fluothiuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Isoproturon Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Isouron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Linuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Metobenzuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Metobromuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Methabenzthiazuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Metoxuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Monolinuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Monuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Neburon Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Parafluron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Siduron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Tebuthiuron Inhbition of Photosynthesis at PSll - Serine 264 Binders Ureas Thiazafluron Inhbition of Photosynthesis at PSll - Serine 264 Binders Amides Chloranocryl=dicryl Inhbition of Photosynthesis at PSll - Serine 264 Binders Amides Pentanochlor Inhbition of Photosynthesis at PSll - Serine 264 Binders Amides PropanilAttorney Reference: TECS-013 Inhbition of Photosynthesis at PSll - Histidine 215 Binders Nitriles Bromofenoxim Inhbition of Photosynthesis at PSll - Histidine 215 Binders Nitriles Bromoxynil Inhbition of Photosynthesis at PSll - Histidine 215 Binders Nitriles Ioxynil Inhbition of Photosynthesis at PSll - Histidine 215 Binders Phenyl-pyridazines Pyridate Inhbition of Photosynthesis at PSll - Histidine 215 Binders Benzothiadiazinone Bentazon PS I Electron Diversion Pyridiniums Cyperquat PS I Electron Diversion Pyridiniums Diquat PS I Electron Diversion Pyridiniums Morfamquat PS I Electron Diversion Pyridiniums Paraquat Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Lactofen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Acifluorfen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Bifenox Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Chlornitrofen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Fomesafen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Fluorodifen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Fluoroglycofen-ethyl Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Fluoronitrofen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Nitrofen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Oxyfluorfen Inhibition of Protoporphyrinogen Oxidase Diphenyl ethers Chlomethoxyfen Inhibition of Protoporphyrinogen Oxidase Phenylpyrazoles Pyraflufen-ethyl Inhibition of Protoporphyrinogen Oxidase N-Phenyl-oxadiazolones Oxadiargyl Inhibition of Protoporphyrinogen Oxidase N-Phenyl-oxadiazolones Oxadiazon Inhibition of Protoporphyrinogen Oxidase N-Phenyl-triazolinones AzafenidinAttorney Reference: TECS-013 Inhibition of Protoporphyrinogen Oxidase N-Phenyl-triazolinones Carfentrazone-ethyl Inhibition of Protoporphyrinogen Oxidase N-Phenyl-triazolinones Sulfentrazone Inhibition of N-Phenyl-imides (procide acitive Protoporphyrinogen Oxidase form) Fluthiacet-methyl Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Butafenacil Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Saflufenacil Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Pentoxazone Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Chlorphthalim Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Cinidon-ethyl Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Flumiclorac-pentyl Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Flumioxazin Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Flumipropyn Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Trifludimoxazin Inhibition of Protoporphyrinogen Oxidase N-Phenyl-imides Tiafenacil Inhibition of Protoporphyrinogen Oxidase Other Pyraclonil Inhibition of Phytoene Desaturase Phenyl ethers Beflubutamid Inhibition of Phytoene Desaturase Phenyl ethers Diflufenican Inhibition of Phytoene Desaturase Phenyl ethers Picolinafen Inhibition of Phytoene Desaturase N-Phenyl heterocycles Flurochloridone Inhibition of Phytoene Desaturase N-Phenyl heterocycles Norflurazon Inhibition of Phytoene Desaturase Diphenyl heterocycles Fluridone Inhibition of Phytoene Desaturase Diphenyl heterocycles Flurtamone Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones Mesotrione Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones Sulcotrione Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones TembotrioneAttorney Reference: TECS-013 Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones Tefuryltrione Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones Bicyclopyrone Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones Fenquinotrione Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Triketones (procide) Benzobicyclon Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Pyrazoles (procide) Benzofenap Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Pyrazoles Pyrasulfotole Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Pyrazoles Topramezone Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Pyrazoles (procide) Pyrazolynate Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Pyrazoles (procide) Pyrazoxyfen Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Pyrazoles Tolpyralate Inhibition of Hydroxyphenyl Pyruvate Dioxygenase Isoxazoles Isoxaflutole Inhibition of Homogentisate Solanesyltransferase Phenoxypyridazine Cyclopyrimorate 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 Synthetase Phosphinic acids Glufosinate-ammonium Inhibition of Glutamine Synthetase Phosphinic acids Bialaphos / bilanafos Inhibition of Dihydropteroate Synthase Carbamate Asulam Inhibition of Microtubule Assembly Dinitroanilines Benefin=benfluralin Inhibition of Microtubule Assembly Dinitroanilines Butralin Inhibition of Microtubule Assembly Dinitroanilines Dinitramine Inhibition of Microtubule Assembly Dinitroanilines EthalfluralinAttorney Reference: TECS-013 Inhibition of Microtubule Assembly Dinitroanilines Fluchloralin Inhibition of Microtubule Assembly Dinitroanilines Isopropalin Inhibition of Microtubule Assembly Dinitroanilines Nitralin Inhibition of Microtubule Assembly Dinitroanilines Prodiamine Inhibition of Microtubule Assembly Dinitroanilines Profluralin Inhibition of Microtubule Assembly Dinitroanilines Oryzalin Inhibition of Microtubule Assembly Dinitroanilines Pendimethalin Inhibition of Microtubule Assembly Dinitroanilines Trifluralin Inhibition of Microtubule Assembly Pyridines Dithiopyr Inhibition of Microtubule Assembly Pyridines Thiazopyr Inhibition of Microtubule Assembly Phosphoroamidates Butamifos Inhibition of Microtubule Assembly Phosphoroamidates DMPA Inhibition of Microtubule Assembly Benzoic acid Chlorthal-dimethyl=DCPA Inhibition of Microtubule Assembly Benzamides Propyzamide=pronamide Inhibition of Microtubule Organization Carbamates Barban Inhibition of Microtubule Organization Carbamates Carbetamide Inhibition of Microtubule Organization Carbamates Chlorbufam Inhibition of Microtubule Organization Carbamates Chlorpropham Inhibition of Microtubule Organization Carbamates Propham Inhibition of Microtubule Organization Carbamates Swep Inhibition of Cellulose Synthesis Triazolocarboxamide Flupoxam Inhibition of Cellulose Synthesis Benzamides Isoxaben Inhibition of Cellulose Synthesis Alkylazines TriaziflamAttorney Reference: TECS-013 Inhibition of Cellulose Synthesis Alkylazines Indaziflam Inhibition of Cellulose Synthesis Nitriles Dichlobenil Inhibition of Cellulose Synthesis Nitriles Chlorthiamid Uncouplers Dinitrophenols Dinosam Uncouplers Dinitrophenols Dinoseb Uncouplers Dinitrophenols DNOC Uncouplers Dinitrophenols Dinoterb Uncouplers Dinitrophenols Etinofen Uncouplers Dinitrophenols Medinoterb Inhibition of Very Long-Chain Fatty Acid Synthesis Azolyl-carboxamides Cafenstrole Inhibition of Very Long-Chain Fatty Acid Synthesis Azolyl-carboxamides Fentrazamide Inhibition of Very Long-Chain Fatty Acid Synthesis Azolyl-carboxamides Ipfencarbazone Inhibition of Very Long-Chain Fatty Acid Synthesis α-Thioacetamides Anilofos Inhibition of Very Long-Chain Fatty Acid Synthesis α-Thioacetamides Piperophos Inhibition of Very Long-Chain Fatty Acid Synthesis Isoxazolines Pyroxasulfone Inhibition of Very Long-Chain Fatty Acid Synthesis Isoxazolines Fenoxasulfone Inhibition of Very Long-Chain Fatty Acid Synthesis Oxiranes Indanofan Inhibition of Very Long-Chain Fatty Acid Synthesis Oxiranes Tridiphane Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Acetochlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Alachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Allidochlor=CDAA Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Butachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Butenachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Delachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Diethatyl-ethylAttorney Reference: TECS-013 Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Dimethachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Dimethenamid Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Metazachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Metolachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Pethoxamid Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Pretilachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Propachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Propisochlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Prynachlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Chloroacetamides Thenylchlor Inhibition of Very Long-Chain Fatty Acid Synthesis α-Oxyacetamides Mefenacet Inhibition of Very Long-Chain Fatty Acid Synthesis α-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 Synthesis Thiocarbamates Tiocarbazil Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Tri-allate Inhibition of Very Long-Chain Fatty Acid Synthesis Thiocarbamates Vernolate Inhibition of Very Long-Chain Fatty Acid Synthesis Benzofurans BenfuresateAttorney Reference: TECS-013 Inhibition of Very Long-Chain Fatty Acid Synthesis Benzofurans Ethofumesate Auxin Mimics Pyridine-carboxylates Picloram Auxin Mimics Pyridine-carboxylates Clopyralid Auxin Mimics Pyridine-carboxylates Aminopyralid Auxin Mimics Pyridine-carboxylates Halauxifen Auxin Mimics Pyridine-carboxylates Florpyrauxifen Auxin Mimics Pyridyloxy-carboxylates Triclopyr Auxin Mimics Pyridyloxy-carboxylates Fluroxypyr Auxin Mimics Phenoxy-carboxylates 2,4,5-T Auxin Mimics Phenoxy-carboxylates 2,4-D Auxin Mimics Phenoxy-carboxylates 2,4-DB Auxin Mimics Phenoxy-carboxylates Clomeprop Auxin Mimics Phenoxy-carboxylates Dichlorprop Auxin Mimics Phenoxy-carboxylates Fenoprop Auxin Mimics Phenoxy-carboxylates Mecoprop Auxin Mimics Phenoxy-carboxylates MCPA Auxin Mimics Phenoxy-carboxylates MCPB Auxin Mimics Benzoates Dicamba Auxin Mimics Benzoates Chloramben Auxin Mimics Benzoates TBA Auxin Mimics Quinoline-carboxylates Quinclorac Auxin Mimics Quinoline-carboxylates Quinmerac Auxin Mimics Pyrimidine-carboxylates Aminocyclopyrachlor Auxin Mimics Other Benazolin-ethyl Auxin Mimics Phenyl carboxylates Chlorfenac=fenac Auxin Mimics Phenyl carboxylates Chlorfenprop Auxin Transport Inhibitor Aryl-carboxylates Naptalam Auxin Transport Inhibitor Aryl-carboxylates Diflufenzopyr-sodium Inhibition of Fatty Acid Thioesterase Benzyl ether Cinmethylin Inhibition of Fatty Acid Thioesterase Benzyl ether MethiozolinAttorney Reference: TECS-013 Inhibition of Serine-Threonine Protein Phosphatase Other Endothal Inhibition of Solanesyl Diphosphate Synthase Diphenyl ether Aclonifen Inhibition of Lycopene Cyclase Triazole Amitrole Unknown Bromobutide Unknown Cumyluron Unknown Difenzoquat Unknown DSMA Unknown Dymron=Daimuron Unknown Etobenzanid Unknown Arylaminopropionic acid Flamprop-m Unknown Fosamine Unknown Methyldymron Unknown Monalide Unknown MSMA Unknown Oleic acid Unknown Oxaziclomefone Unknown Pelargonic acid Unknown Pyributicarb Unknown Quinoclamine Unknown Acetamides Diphenamid Unknown Acetamides Naproanilide Unknown Acetamides Napropamide Unknown Benzamide Tebutam Unknown Phosphorodithioate Bensulide Unknown Chlorocarbonic acids Dalapon Unknown Chlorocarbonic acids Flupropanate Unknown Chlorocarbonic acids TCA Unknown Trifluoromethanesulfonanilides Mefluidide Unknown Trifluoromethanesulfonanilides Perfluidone Unknown CAMA Unknown Cacodylic acidAttorney Reference: TECS-013 APPENDIX 3

[0194] Shown below is Appendix 3. Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying Active xim, ,Attorney Reference: TECS-013 Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying Active in, er, )- nAttorney Reference: TECS-013 Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying Active nAttorney Reference: TECS-013 Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying Active c,Attorney Reference: TECS-013 Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying Active ,Attorney Reference: TECS-013 Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying ActiveAttorney Reference: TECS-013 Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying Active ncAttorney Reference: TECS-013WO Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying ActiveAttorney Reference: TECS-013WO Main Group and Primary Site of Sub-group, class or Active Ingredients Action exemplifying ActiveMain Group and Primary Site of Sub-group, class or Active IngredientsAttorney Reference: TECS-013WO UNE* Botanical essence including Chenopodium ambrosioides near ambrosioides synthetic, extracts and unrefined extract oil

[0195] Notwithstanding the appended claims, aspects of the present disclosure are further provided in the following numbered clauses: 1. A method for inhibiting apyrase, comprising contacting the apyrase with a compound of formula (I): wherein:G is monocyclic aryl or monocyclic heteroaryl; wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb;Attorney Reference: TECS-013WO Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10 aryl, C6-C10 arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, -NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6alkyl or C3-8cycloalkyl; each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd; provided that the compound does not have the formulaAttorney Reference: TECS-013WO 2. The method of clause 1, wherein G comprises a six-membered aryl or six-membered heteroaryl ring. 3. The method of clause 2, wherein G is an optionally substituted phenyl. 4. The method of clause 3, wherein G is substituted phenyl. 5. The method of clause 4, wherein the compound has formula (Ia):6. The method of clause 4, wherein the compound has formula (Ib): wherein Ar is optionally7. The method of clause 6, wherein Ar in formula (Ib) is unsubstituted, substituted with an Ragroup of C1-6 alkyl, or substituted with an Rbgroup of halogen. 8. The method of clause 2, wherein G is an optionally substituted biphenyl group. 9. The method of clause 8, wherein the compound has the formula (Ib1):10. The method of clause 1, wherein G is optionally substituted pyrimidinyl.Attorney Reference: TECS-013WO 11. The method of clause 10, wherein the compound has formula (Ic): wherein Ar is optionally12. The method of clause 11, wherein Ar in formula (Ic) is unsubstituted, substituted with an Ragroup of C1-6alkyl, or substituted with an Rbgroup of halogen. 13. The method of any one of clauses 1-12, wherein G and its substituents have 6 to 20 non- hydrogen atoms. 14. The method of any one of clauses 1-13, wherein Z is substituted phenyl. 15. The method of clause 14, wherein Z is phenyl substituted with an optionally substituted aryl or heteroaryl group. 16. The method of clause 15, wherein Z is phenyl substituted with an optionally substituted alkyl group. 17. The method of clause 16, wherein Z is phenyl substituted with an Rbgroup. 18. The method of clause 17, wherein the compound has the formula (1d):19. The method of clause 17, wherein the compound has the formula (1e):Attorney Reference: TECS-013WO 20. The method of clause 17,with an Rbgroup of halogen or -CF3. 21. The method of any one of clauses 1-13, wherein Z is optionally substituted monocyclic heteroaryl. 22. The method of clause 21, wherein Z is optionally substituted pyridyl. 23. The method of clause 21, wherein Z is optionally substituted pyrimidyl. 24. The method of any one of clauses 1-13, wherein Z and R1together form a 5-membered or 6-membered heterocyclylalkyl ring. 25. The method of any one of clauses 1-13, wherein Z is selected from the group consisting of , , .Attorney Reference: TECS-013WO 26. The method of any one of clauses 1-25, wherein Z and its substituents have 6 to 20 non- hydrogen atoms. 27. The method of any one of clauses 1-26, wherein contacting the apyrase comprises treating a crop with the compound. 28. The method of clause 27, further comprising treating the crop with a pesticide. 29. The method of clause 28, wherein the pesticide is selected from acaricides, fungicides, herbicides, insecticides, molluscicides, nematocides, or a combination thereof. 30. The method of clause 29, wherein the pesticide comprises a fungicide. 31. The method of clause 28, wherein the pesticide comprises an herbicide. 32. The method of clause 31, wherein the herbicide comprises glyphosate. 33. The method of clause 29, 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 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, 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. 34. A composition, comprisingAttorney Reference: TECS-013WO a fungicide; a phytologically acceptable carrier; and a compound of formula (I): wherein:G is monocyclic aryl or wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10aryl, C6-C10arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)N RcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -O C(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl which may optionally include one or more of the same or different additional heteroatoms and whichAttorney Reference: TECS-013WO may optionally be substituted with one or more of the same or different group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6 alkyl or C3-8 cycloalkyl; and each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd. 35. The composition of clause 34, wherein the composition comprises from about 1 to about 80 weight percent of the compound. 36. The composition of clause 35, wherein the composition is a suspension formulation. 37. The composition of clause 36, wherein the composition comprises from about 1 to about 50 weight percent of the compound. 38. The composition of clause 37, further comprising sodium polycarboxylate. 39. The composition of clause 34, further comprising biocides. 40. The composition of clause 35, further comprising organosilicone antifoam emulsion. 41. The composition of clause 38, wherein the composition is a wettable powder. 42. The composition of clause 34, wherein the composition is an emulsifiable concentrate. 43. The composition of clause 40, further comprising tristyrylphenol ethoxylates. 44. The composition of clause 34, wherein the composition is an oil dispersible concentrate. 45. A pesticidal composition, comprising a pesticide; a phytologically acceptable carrier; and a compound of formula (I):Attorney Reference: TECS-013WO wherein: G is monocyclic aryl orwherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10 aryl, C6-C10 arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)N RcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -O C(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6alkyl or C3-8cycloalkyl; and each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd.Attorney Reference: TECS-013WO 46. The pesticidal composition of clause 45, wherein the pesticide comprises an acaricide, fungicide, herbicide, insecticide, molluscicide, nematocide, or a combination thereof. 47. A fungicidal composition, comprising a fungicide; a phytologically acceptable carrier; and a compound of formula (I): (I) wherein: G is monocyclic aryl or monocyclic heteroaryl; wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C5-C10 aryl, C6-C10 arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)N RcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -O C(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORAttorney Reference: TECS-013WOd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6 alkyl or C3-8 cycloalkyl; each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd. 48. The composition of clause 47, 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, 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.

[0196] In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments 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.

Claims

Attorney Reference: TECS-013WO CLAIMS What Is Claimed Is:

1. A method for inhibiting apyrase, comprising contacting the apyrase with a compound of formula (I): wherein:G is monocyclic aryl or wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C5-C10 aryl, C6-C10 arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, -NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc;Attorney Reference: TECS-013WO each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6 alkyl or C3-8 cycloalkyl; each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd; provided that the compound does not have the formula .

2. The method of claim 1, wherein G comprises a six-membered aryl or six-membered heteroaryl ring.

3. The method of claim 2, wherein G is an optionally substituted phenyl or optionally substituted biphenyl group..

4. The method of claim 3, wherein the compound has a formula (Ia): formula (Ib):wherein Ar is optionallyand / or formula (Ib1):Attorney Reference: TECS-013WO5. The method of claim 1, wherein G is optionally substituted pyrimidinyl.

6. The method of claim 5, wherein the compound has formula (Ic): wherein Ar is selected from aryl and heteroaryl, whereinthe substitutions are selected from C1-6alkyl and halogen.

7. The method of any one of claims 1-6, wherein G and its substituents have 6 to 20 non- hydrogen atoms.

8. The method of any one of claims 1-7, wherein Z is phenyl substituted with a group selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkyl, Rb, or a combination thereof.

9. The method of claim 8, wherein the compound has a formula selected from formula (1d):and formula (1e):Attorney Reference: TECS-013WO 10. The method of claim 8, wherein Z is phenyl substituted with an Rbgroup of halogen or - CF3 or Z is optionally substituted monocyclic heteroaryl, such as optionally substituted pyridyl or optionally substituted pyrimidyl.

11. The method of any one of claims 1-7, wherein Z and R1together form a 5-membered or 6-membered heterocyclylalkyl ring.

12. The method of any one of claims 1-7, wherein Z is selected from the group consisting of , , .

13. The method of any one of claims 1-12, wherein Z and its substituents have 6 to 20 non- hydrogen atoms.

14. The method of any one of claims 1-13, wherein contacting the apyrase comprises treating a crop with the compound.

15. The method of claim 14, further comprising treating the crop with a pesticide.

16. The method of claim 28, wherein the pesticide is selected from acaricides, fungicides, herbicides, insecticides, molluscicides, nematocides, or a combination thereof.Attorney Reference: TECS-013WO 17. A composition, comprising a fungicide; a phytologically acceptable carrier; and a compound of formula (I): wherein:G is monocyclic aryl or wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6 alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6 alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10aryl, C6-C10arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)N RcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -O C(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl whichAttorney Reference: TECS-013WO 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6 alkyl or C3-8 cycloalkyl; each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd.

18. The composition of claim 17, wherein the composition comprises from about 1 to about 80 weight percent of the compound.

19. A pesticidal composition, comprising a pesticide; a phytologically acceptable carrier; and a compound of formula (I): wherein:G is monocyclic aryl or monocyclic heteroaryl; wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6alkyl; or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10aryl, C6-C10arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2,Attorney Reference: TECS-013WO =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)N RcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -O C(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6 alkyl or C3-8 cycloalkyl; each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd.

20. The pesticidal composition of claim 19, wherein the pesticide comprises an acaricide, fungicide, herbicide, insecticide, molluscicide, nematocide, or a combination thereof.

21. A fungicidal composition, comprising a fungicide; a phytologically acceptable carrier; and a compound of formula (I): (I) wherein: G is monocyclic aryl or monocyclic heteroaryl; wherein G is optionally substituted with 1, 2, or 3 groups selected from Raand Rb; Z is selected from the group consisting of monocyclic aryl, bicylic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and C1-6alkyl; wherein Z is optionally substituted with 1, 2 or 3 groups selected from Raand Rb; R1is hydrogen or C1-6alkyl;Attorney Reference: TECS-013WO or Z and R1together form a 5-, 6-, or 7-membered ring selected from heterocyclylalkyl optionally substituted with 1, 2 or 3 groups selected from Raand Rb; each Rais independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C5-C10 aryl, C6-C10 arylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocyclylalkyl, 4-11 membered heterocyclylalkylalkyl, 5-10 membered heteroaryl and 6-16 membered heteroarylalkyl; each Rais optionally substituted with one or more groups selected from Rband Re; each Rbis independently selected from the group consisting of =O, -ORd, -OCF3, - OCF2H =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CF2H, -CN, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, - NHS(O)2Rd, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)N RcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -O C(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -NHSO2Rd, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc; each Rcis independently hydrogen, Ra, or, alternatively, two Rcare taken together with the nitrogen atom to which they are bonded to form a 5 to 8-membered heterocyclylalkyl 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 group selected from Ra, =O, halogen, and Re; each Rdis independently C1-6alkyl or C3-8cycloalkyl; each Reis independently C1-6 alkyl, C3-8 cycloalkyl, -C(O)Rd, and -C(O)ORd.

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