Insect neuropeptide 3

Abstract

The present invention relates to natural or natural-like analogs of insect pyrokinin neuropeptide [Hy]-NADEDQQQSVDFTPRL-[NH2] (SEQ ID NO: 2) having activity against insects, such as hemiptera, diptera, lepidoptera, cockroaches and / or coleopteran insects, such as aphids, moths and fruit flies, and the use of these natural or natural-like analogs as insect control agents, such as insecticides, and plant protection agents.

Description

Technical Field

[0001] The present invention relates to natural or nature-like analogs of insect pyrokinin neuropeptides having activity against insects (e.g. Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera, such as aphids, moths and fruit flies), and their use as insect control agents (e.g. pesticides) and plant protection agents. Background Art

[0002] With the global reliance on broad-spectrum insecticides, whose damaging effects are well documented, there is an increasing need to develop more environmentally friendly, target-specific insecticides for the protection of valuable crop plants. The development and use of neuropeptides and their synthetic analogs offer a promising avenue for the development of more environmentally friendly and target-specific insecticides.

[0003] In insects, neuropeptides are regulatory peptides that play functional roles in growth and development, behavior and reproduction, metabolism and homeostasis, and muscle movement. The insect neuropeptide family is large and includes insect kinins and CAPA (CAPA, CAP2b, CAPA3) neuropeptides, AKH peptides, and pyrokinins.

[0004] Due to their high specificity, insect neuropeptides and their cognate receptors (G-protein coupled receptors, GPCRs) can be developed for use in insecticides to selectively reduce the fitness of target pest insects while minimizing adverse environmental effects and minimizing damage to other non-target species such as pollinators, whose populations have been drastically reduced due to the use of pesticides / insecticides.

[0005] Attempts have been made in the art to provide modified synthetic analogs of such insect neuropeptides for use as targeted insecticides, which have shown promising results. However, while these modified peptides are desirable and effective, it can be challenging to bring these modified peptides to market in many regions where their use is strictly regulated.

[0006] The present invention aims to solve one or more of the above problems and to provide novel natural pyrokinin neuropeptides and natural-like variants or analogs thereof for use as insect control agents and plant protection agents. Summary of the invention

[0007] The inventors have discovered novel pyrokinins and their naturally-like variants or analogs which have insecticidal activity against insects (e.g., Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera) and are therefore potentially useful as pest control agents or insecticides while having little or no effect on important pollinator species (e.g., bees).

[0008] Therefore, in a first aspect, the present invention provides a pesticidal compound having the following formula (I) or a salt or solvate thereof:

[0009] R 1 -Y 1 -ZY 2 -R 2

[0010] (I)

[0011] in:

[0012] R 1 is hydrogen (which may be designated as "H-" or "Hy-"), C 1-4 Alkyl (e.g., methyl, ethyl, propyl, butyl), formyl, acyl, fatty acyl, sugar moiety, phosphate or sulfate, or R 1 is the pyroglutamic acid group of the formula:

[0013]

[0014] Any alkyl, formyl, acyl or fatty acyl group may be optionally substituted with one or more oxo or C 1-6 Alkyl or sugar moieties, phosphate or sulfate group substitution;

[0015] Y 1 Absent or a peptide consisting of 1 to 2 amino acids;

[0016] Z is a peptide according to the formula

[0017] NADEDQQQSVDFTPRL(SEQ ID NO:1);

[0018] Y 2 Absent or a peptide consisting of 1 to 2 amino acids;

[0019] R 2 NH2、NR 2a H, NR 2a R 2b , OH or OR 2a ; where R 2a and R 2b If present, each is independently C 1-6 - alkyl (eg methyl, ethyl, propyl, butyl, pentyl or hexyl).

[0020] In another aspect, there is provided a composition comprising a compound as defined herein or a salt thereof in admixture with one or more solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifiers or synergists. Suitably, the composition is an agricultural composition, an insect control composition or a plant protection composition.

[0021] In another aspect, there is provided a use of a compound or salt thereof as defined herein, or a composition as defined herein, as an insect control agent. The use may be as an insecticide against insects encoding pyrokinin. The use may be as an insecticide against Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera, preferably Hemiptera, Diptera and / or Lepidoptera, most preferably Lepidoptera such as moths.

[0022] In another aspect, there is provided a method of increasing insect mortality, the method comprising contacting an insect population with a compound as defined herein or a salt thereof, or a composition as defined herein. Suitably, the insect is an insect encoding a pyrokinin, such as a Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera, preferably a Hemiptera, Diptera and / or Lepidoptera, most preferably a Lepidoptera, such as a moth.

[0023] In another aspect, a method for increasing the mortality of Hemiptera, Diptera, Lepidoptera, Blattaria and / or Coleoptera insects is provided, the method comprising contacting a Hemiptera, Diptera, Lepidoptera, Blattaria and / or Coleoptera insect population with a compound or salt thereof as defined herein or a composition as defined herein. Preferably, the insect is a Lepidoptera insect, such as a moth.

[0024] In another aspect, there is provided the use of a compound as defined herein or a salt thereof or a composition as defined herein as a plant protection agent for protecting plants from an insect encoding said pyrokinin. Preferably, the insect is a Lepidoptera insect, such as a moth.

[0025] In another aspect, there is provided the use of a compound as defined herein or a salt thereof, or a composition as defined herein, as a plant protection agent for protecting plants from insects of the orders Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera, preferably Hemiptera, Diptera and / or Lepidoptera, most preferably Lepidoptera, such as moths.

[0026] In another aspect, there is provided a method of inhibiting infestation of a plant by an insect encoding a pyrokinin, the method comprising contacting the plant with a compound or salt thereof as defined herein or a composition as defined herein. Suitably, the compound or composition is applied to the plant when the plant is free or substantially free of insects encoding a pyrokinin.

[0027] In another aspect, there is provided a method of inhibiting infestation of a plant by Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera, the method comprising contacting the plant with a compound as defined herein or a salt thereof, or a composition as defined herein. Suitably, the compound or composition is applied to the plant when the plant is free or substantially free of Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera. Preferably, the insect is selected from Hemiptera, Diptera and / or Lepidoptera, most preferably Lepidoptera, such as a moth.

[0028] In another aspect, there is provided a method of reducing infestation of a plant by pyrokinin-encoding insects, or a method of reducing the load of pyrokinin-encoding insects on a plant, the method comprising contacting the plant with a compound or salt thereof as defined herein, or a composition as defined herein.

[0029] On the other hand, there is provided a method for reducing the infestation of plants by Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects, or a method for reducing the load of Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera insects on plants, the method comprising contacting the plant with a compound as defined herein or a salt thereof or a composition as defined herein. Preferably, the insect is selected from Hemiptera, Diptera and / or Lepidoptera insects, most preferably Lepidoptera insects, such as moths. In one embodiment, the compounds, compositions and agents of the present invention are suitably active against the moth species Plutella xylostella. In one embodiment, the compounds, compositions and agents of the present invention are suitably active against the moth species Spodoptera frugiperda. In one embodiment, the compounds, compositions and agents of the present invention are suitably active against the looper species Trichoplusia ni.

[0030] Suitable insects encoding pyrokinin include Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera, preferably Hemiptera, Diptera and / or Lepidoptera. In a preferred embodiment, the insect encoding pyrokinin is a Lepidoptera insect, such as a moth.

[0031] In another aspect, there is provided a method for producing a pesticidal compound according to the first aspect, the method comprising:

[0032] (a) Chemically synthesizing the insecticidal compound of formula (I) or its precursor.

[0033] In one embodiment, the chemical synthesis comprises the method described in the examples. In one embodiment, the chemical synthesis comprises Figure 2 The methods and steps shown.

[0034] Aspects of the invention and further features of embodiments will now be defined under the following headings.Any feature in any section may be combined with any aspect of the embodiments in any feasible combination. DETAILED DESCRIPTION

[0035] definition

[0036] Throughout the present specification and claims, the conventional three-letter and one-letter codes for naturally occurring amino acids are used, i.e., A (Ala), G (Gly), L (Leu), I (Ile), V (Val), F (Phe), W (Trp), S (Ser), T (Thr), Y (Tyr), N (Asn), Q (Gln), D (Asp), E (Glu), K (Lys), R (Arg), H (His), M (Met), C (Cys), and P (Pro).

[0037] "Amino acid" mentioned herein may refer to naturally occurring amino acids or any other amino acids, including synthetic amino acids and non-protein amino acids. "Naturally occurring" herein refers to the 20 amino acids encoded by the standard genetic code, sometimes referred to as protein amino acids.

[0038] The term amino acid is an abbreviation for α-amino [α-amino] carboxylic acid. Each molecule contains a central carbon atom, called the α-carbon, to which are attached an amino group and a carboxyl group. The remaining two bonds to the α-carbon atom are usually satisfied by a hydrogen (H) atom and a side chain, as shown below by R:

[0039]

[0040] Unless otherwise indicated, the amino acid residues in the peptides of the present invention are in the L-configuration. As used herein, the terms "polypeptide", "protein", "peptide" are used interchangeably and refer to a polymeric form of amino acids of any length, which may include coded amino acids and non-coded amino acids. As used herein, amino acid residues will be indicated as above by their full names or according to the standard three-letter or one-letter amino acid code.

[0041] Symbol C x-xx Refers to the number of carbon atoms in the functional group. The number at the "x" position is the lowest number of carbon atoms, and the number at the "xx" position is the highest number of carbon atoms. For example, C 1-6 -Alkyl refers to an alkyl group as defined herein having 1 to 6 carbon atoms.

[0042] As used herein, the symbols I, n or t are associated with various alkyl groups in a conventional manner. Specifically, the suffix refers to the arrangement of atoms and indicates a straight chain ('n') or branched chain ('i' or 't') alkyl group.

[0043] The term "alkyl" as used herein refers to a saturated straight or branched monovalent hydrocarbon radical, wherein the alkyl group may be optionally substituted. The number of carbon atoms in the alkyl group may be specified using the symbols described above, for example, when there are 1 to 8 carbon atoms, the term C may be used. 1-8-alkyl. Examples of alkyl groups include methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), 2-propyl (i-Pr, isopropyl, -CH(CH3)2) and 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3).

[0044] An "alkylene," "alkenylene," or "alkynylene" group is an alkyl, alkenyl, or alkynyl group that is positioned between and serves to connect two other chemical groups. Thus, an "alkylene," "alkenylene," or "alkynylene" group is an alkyl, alkenyl, or alkynyl group that is positioned between and serves to connect two other chemical groups. 1-6 "Alkylene" refers to a straight chain saturated divalent hydrocarbon radical of one to six carbon atoms or a branched chain saturated divalent hydrocarbon radical of three to six carbon atoms. Example alkylene groups include methylene (-CH2-), 1,1-ethylene (-CH(CH3)-), 1,2-ethylene (-CH2CH2-), 1,1-propylene (-CH(CH2CH3)-), and 2,2-propylene (-C(CH3)2-).

[0045] As used herein, the term "alkenyl" refers to a straight or branched monovalent hydrocarbon radical having at least one site of unsaturation (i.e., a carbon-carbon double bond). Alkenyl groups may be optionally substituted and include groups having "cis" and "trans" orientations or alternatively "E" and "Z" orientations. The number of carbon atoms in an alkenyl group may be specified using the symbols described above, for example, when there are 2 to 8 carbon atoms, the term C may be used. 2-8 -Alkenyl. Example alkenyl groups include, but are not limited to, vinyl (-CH=CH2) and prop-1-enyl (-CH=CHCH3).

[0046] In the chemical structures drawn in this article, or The presence of indicates a point of attachment or a radical, for example, the radical in question associated with various functional groups.

[0047] The term "comprising" is used in the present description and claims, which does not exclude other elements or steps. When referring to a singular noun, an indefinite or definite article is used, for example "a" or "an", "the", this includes the plural form of the noun unless otherwise stated.

[0048] As used herein, the term "about" when referring to a measurable value such as a parameter, amount, duration, etc., is intended to include variations of + / -10% or less, preferably + / -5% or less, more preferably + / -1% or less, and still more preferably + / -0.1% or less of the specific value, as long as these variations are suitable for implementation in the disclosed invention. It should be understood that the value referred to by the modifier "about" itself is also specifically and preferably disclosed.

[0049] "Plant" as used herein refers to a whole plant or a part thereof, including fresh fruits, vegetables and seeds. A plant or plant part may be a living plant or a part thereof. In addition, the term "plant" as used herein encompasses whole plants, ancestors and offspring of plants, and plant parts, including seeds, buds, stems, leaves, roots (including tubers), flowers, and tissues and organs, wherein each of the aforementioned comprises a target gene / nucleic acid. The term "plant" also encompasses plant cells, suspension cultures, callus, embryos, meristem regions, gametophytes, sporophytes, pollen and microspores, wherein each of the aforementioned also comprises a target gene / nucleic acid.

[0050] As used herein, "crop" refers to a plant species or variety grown for harvest as food, livestock feed, fuel raw material, or for any other economic purpose. As non-limiting examples, the crop may be corn, cereals such as wheat, rye, barley, and oats, sorghum, rice, sugar beets and fodder beets, fruits such as pome fruits (e.g., apples and pears), citrus fruits (e.g., oranges, lemons, limes, grapefruits, or mandarins), stone fruits (e.g., peaches, nectarines, or plums), nuts (e.g., almonds or walnuts), soft fruits (e.g., cherries, strawberries, blackberries, or raspberries), plantaginaceae or grapevines, leguminous crops such as beans, lentils, peas, and soybeans, oilseed crops such as sunflowers, safflower, rapeseed, canola, castor beans, or olives, gourds, or other crops. Cucurbitaceae, such as cucumbers, melons or pumpkins, fiber plants, such as cotton, flax, fuel crops (such as sugar cane, miscanthus or switchgrass), vegetables (such as potatoes, tomatoes, peppers, lettuce, spinach, onions, carrots, eggplant, asparagus or cabbage), ornamental plants (such as flowers (such as petunias, geraniums, roses, tulips, lilies or chrysanthemums), shrubs, broad-leaved trees (such as poplars or willows) and evergreen trees (such as conifers), grasses (such as lawns, turf or pasture) or other useful plants (such as coffee, tea, tobacco, hops, peppers, rubber or latex plants).

[0051] As used herein, "pest" refers to organisms that are harmful to plants, animals, humans or human affairs, including but not limited to crop pests such as insects (defined below), household pests or insects such as cockroaches, ants, etc., and disease vectors such as the anopheles mosquito.

[0052] As used herein, "pest infection" or "pest disease" refers to any inflammatory condition, disease, or disorder in a living organism, such as a plant, animal, or human, caused by a pest.

[0053] "Active substance", "active ingredient" or "effective ingredient" are used interchangeably herein and mean any biological, biochemical or chemical element and its derivatives, fragments or compounds based thereon, including microorganisms, which has a general or specific effect on pests on a subject, in particular insect pests on plants, plant parts or plant products (whether naturally occurring or manufactured, including any impurities inevitably produced during the manufacture of the same).

[0054] As used herein, the terms "effective amount" and "effective dosage" refer to the amount necessary to achieve the desired result.

[0055] "Insects" as used herein are insects in a broad, colloquial sense, including all species of the general phylum Panarthropoda (classification Systema Naturae [natural classification system], Brands, SJ (compilation) 1989-2005. Systema Naturae [natural system] 2000. Amsterdam, the Netherlands [http: / / sn2000.taxonomy.nl / ]), including the phyla Arthropoda, Tardigrades and Clawed Animals; it includes all different stages of the life cycle, such as but not limited to eggs, larvae, nymphs, pupae and adults. Suitable insect pests are defined elsewhere herein.

[0056] As used herein, "insecticide compound" refers to a compound that is biologically active against insects (as defined above), including but not limited to compounds that can kill insects, larvicides, insect growth regulators, behavior-changing compounds, attractants, repellents, pheromones, kairomones, egotropes, and insect pathogenic fungi, viruses, and proteins. The insecticide preferably exerts its biological activity by contacting the compound with the insect without being ingested by the insect. It includes not only ready-to-use compounds or compound formulations, but also precursors in inactive forms that can be activated by external factors. Possibly, the insecticide can be combined with materials used in conjunction, such as synergists or safeners, flavorings, or odor compositions. Preferably, the compound is contained in a carrier as defined above. "Contained in a carrier" as used herein refers to being combined or contained in a carrier by, for example, but not limited to, embedding, encapsulation, and adsorption.

[0057] Unless the context requires otherwise, throughout this specification, including the following claims, the words "comprise" and "include" and variations such as "comprises", "comprising" and "including", will be understood to imply the inclusion of stated integers or steps or groups of integers or steps but not the exclusion of any other integers or steps or groups of integers or steps.

[0058] It must be noted that, as used in the specification and the appended claims, the singular forms "a / an" and "the" include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when a value is expressed as an approximation by using the antecedent "about," it will be understood that the particular value forms another embodiment. The term "about" in connection with a numerical value is optional, and means, for example, + / - 10%.

[0059] Compounds of the present invention

[0060] Specific compounds of the present invention include, for example, compounds of formula (I), wherein, unless otherwise specified, R 1 , Y 1 , Y 2 , R 2 Each of and any associated substituents have the meanings defined above or in any of paragraphs (1) to (12) below:-

[0061] (1)R 1 is selected from hydrogen, acyl or fatty acyl, or phosphate or sulfate, or R 1 is the pyroglutamic acid group of the formula:

[0062]

[0063] wherein the acyl or fatty acyl group is optionally substituted with a sugar moiety, phosphate or sulfate.

[0064] (2)R 1 Selected from hydrogen, formyl, acetyl (Ac), propionyl, butanoyl, palmitoyl [palmitoyl], butyryl, cerotoyl, decanoyl, docosenoyl, dodecanoyl, tauroyl, heptanoyl, hexanoyl, eicosanoyl, eicosenoyl, tetracosanoyl, linoleoyl, lipoyl, myristoyl, nonanoyl, octadecanoyl, octanoyl, palmitoyl, stearoyl, undecanoyl and valeryl.

[0065] (3)R 1 is selected from hydrogen, acetyl or palmitoyl, or R 1 is the pyroglutamic acid group of the formula:

[0066]

[0067] (4)R 1 Selected from hydrogen or palmitoyl.

[0068] (5)R 1 It's hydrogen.

[0069] (6)R 1 is the pyroglutamic acid group of the formula:

[0070]

[0071] (7)Y 1 Absent or a peptide consisting of 1 or 2 amino acid residues.

[0072] (8)Y 1 Does not exist.

[0073] (9)Y 2 Absent or a peptide consisting of 1 or 2 amino acid residues.

[0074] (10)Y 2 Does not exist.

[0075] (11)R 2 NH2、NR 2a H, NR 2a R 2b or OH, where R 2a and R 2b If present, each is independently C 1-6 - alkyl (eg methyl, ethyl, propyl, butyl, pentyl or hexyl).

[0076] (12)R 2 It's NH2.

[0077] Suitably, R 1 is as defined in any of paragraphs (1) to (6) above. More suitably, R 1 is as defined in any of paragraphs (3) to (6) above. Most suitably, R 1 is as defined in paragraph (4) or (5) above.

[0078] Appropriately, Y 1 or Y 2 is as defined in any of paragraphs (7) to (10) above. Most suitably, Y 1 or Y 2 is as defined in paragraph (8) or (10) above.

[0079] Suitably, R 2 is as defined in paragraph (11) or (12) above. Most suitably, R 2 is as defined in paragraph (12) above.

[0080] In a preferred embodiment, R 1 It is hydrogen, Y1 and Y 2 does not exist, and R 2 It's NH2.

[0081] In a preferred embodiment, R 1 It is hydrogen, Y 2 Does not exist, Y 1 is one or two amino acids, and R 2 It's NH2.

[0082] In a preferred embodiment, R 1 It is hydrogen, Y 1 Does not exist, Y 2 is one or two amino acids, and R 2 It's NH2.

[0083] Further explanation of the compounds of the present invention

[0084] R 1 and R 2

[0085] The end groups at the N-terminus and C-terminus of the peptide backbone are designated as R 1 and R 2 Therefore, R 1 With Y 1 The nitrogen atom of the N-terminal amino group is bonded to 2 With Y 2 Bonded to the C-terminal carbonyl carbon atom.

[0086] The compounds of the invention may include further functionalization, suitably at the N or C terminus. Suitably, the compounds may be functionalized to increase stratum corneum permeability or to increase stability. Suitably, the compounds may be functionalized with aromatic groups, aliphatic groups or lipophilic groups. Thus, suitably, R 1 It may be an aromatic group, a heteroaromatic group, an aliphatic group or a lipophilic group.

[0087] In certain embodiments, the compound can be functionalized with a lipophilic group such as a fatty acyl group. Fatty acyl groups include, but are not limited to, palmitoyl, butyroyl, cetyl, decanoyl, docosenoyl, dodecanoyl, tauropyl, heptanoyl, hexanoyl, eicosanoyl, eicosenoyl, tetracosanoyl, linoleoyl, lipoyl, myristoyl, nonanoyl, octadecanoyl, octanoyl, palmitoleoyl, stearoyl, undecanoyl, and valeryl. Thus, suitably, R 1 The group may be palmitoyl ([Palm]), that is:

[0088]

[0089] In one embodiment, the compound can be functionalized with an acyl group. An "acyl" group is a group of the formula R 3a -C(O)- group, where R 3a It is C 1-6 Alkyl, such as formyl, acetyl (Ac), propionyl, butyric acid acyl, or wherein R 3a is benzoyl. Suitably, R 3a The group may be R 1b -C(O)-, such as acetyl (Ac), that is:

[0090]

[0091] In certain embodiments, R 1 The groups may be substituted with sugar moieties.

[0092] In certain embodiments, one or more amino acid residues in peptides Y and Z may be naturally modified with a sugar moiety, i.e., the amino acid residues may be "sugar-modified analogs." For example, the sugar may be part of a Ser or Thr side chain modification (glycosylation) or a Lys or Arg side chain modification (glycosylation).

[0093] The sugar moiety discussed herein can be a monosaccharide or a disaccharide. The example of a monosaccharide includes glucose, 6-deoxyglucose, mannose, galactose, glucosamine, galactosamine, N-acetylglucosamine, N-acetylgalactosamine, glucuronic acid, allose, altrose, gulose, idose, fucose, talose, ribose, deoxyribose, arabinose, xylose, lyxose, ribulose, xylulose, fructose, psicose, sorbose or tagatose. The example of a disaccharide includes sucrose, lactose, lactulose, allolactose, maltose, isomaltose, isomaltulose, trehalose, cellobiose, kojibiose, nigerose, sophorose, laminaribiose, gentiobiose, thiomaltose, mannobiose or its N-, C- or S-glycoside derivatives. Most suitably, the sugar moiety is selected from glucosamine or galactosamine. The sugar may be present as an N-terminal modification or as part of a Ser side chain modification. 1 The groups may be substituted with phosphate or sulfate.

[0094] In certain embodiments, one or more amino acid residues in peptides Y and Z may be naturally modified with phosphate or sulfate. For example, the phosphate or sulfate may be part of a side chain modification, i.e., the amino acid may be phosphorylated or sulfated.

[0095] R 1 selected from hydrogen (which may not be noted in a particular peptide sequence, or may be designated instead as "H-" or "Hy-"), C 1-4 Alkyl (e.g., methyl, ethyl, propyl, butyl), -N(R 1a )-C(=N+ (R 1b )(R 1c ))NR 1d R 1e or -C(=N + (R 1b )(R 1c ))NR 1d R 1e ; where R 1a , R 1b , R 1c , R 1d and R 1e are each independently selected from hydrogen or C 1-4 Alkyl (eg, methyl, ethyl, propyl, butyl), preferably hydrogen or methyl.

[0096] In some embodiments, if R 1 Yes-C(=N + (R 1b )(R 1c ))NR 1d R 1e ; R 1a , R 1b , R 1c , R 1d and R 1e Each is a methyl group, that is, R 1 Yes-C(=N + Me2)NMe2.

[0097] When R 1 = "H" (or "Hy";), which usually represents the free primary amino group at the N-terminus. The other hydrogen atom of the N-terminal amino group is usually unchanged, regardless of R 1 Exceptionally, when the N-terminal residue is N-methylated, even if the N-terminal residue has a secondary amine group, R 1 can still be represented as H. Therefore, the N-methylated leucine residue at the N-terminus can be represented as R 1 -[n-me-L]-, where R 1 is H. However, it can also be simply expressed as R 1 -L-, where R 1 is a methyl group, and another hydrogen atom is not shown.

[0098] In some embodiments, an N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue can undergo conversion to form a pyroglutamic acid terminal group [pyr]:

[0099]

[0100] The N-terminal glutamine (Q) or glutamic acid (E) residue may undergo this conversion in biological systems by reacting with certain enzymes. This conversion can also be achieved synthetically.

[0101] Therefore, Y 1 The peptide (if present) or the Z peptide may also contain an N-terminal [pyr] group:

[0102]

[0103] The N-terminal [pyr] group can be formed due to the cyclization of the N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue to form a pyroglutamate terminal group. Since this conversion can occur under certain biological conditions, it is considered to be a naturally occurring modification of the N-terminal glutamine (Gln or Q) or N-terminal glutamic acid (Glu or E) residue.

[0104] Suitably, R 2 NH2、NR 2a H, NR 2a R 2b OR 2a ; where R 2a and R 2b Each is as defined herein. Preferably R 2 It's NH2.

[0105] Specific examples of pyrokinins according to the present invention include:

[0106]

[0107] or a salt or solvate thereof.

[0108] In some embodiments, the compounds of the invention may be in the form of a salt or a solvate (eg, a hydrate).

[0109] The compounds of the invention may be provided in combination with one or more additional active pesticides such as those described herein.

[0110] Y 1 and Y 2

[0111] The peptide may comprise one or two further peptide groups located between the terminal R1 and R2 groups at the N and C termini respectively. Suitably, these groups are Y 1 and Y 2 If present, these groups are located on either side of the Z peptide group.

[0112] In one embodiment, Y 1 and Y 2 The group does not exist.

[0113] In one embodiment, the compound comprises only Y 1 In one embodiment, the compound comprises only Y 2 Group.

[0114] In one embodiment, the compound comprises Y 1 and Y 2 Group.

[0115] Suitably, when present, the Y group comprises one or two amino acids. Suitably, the Y group may comprise any amino acid, suitably selected from: M, R, G and K.

[0116] In one embodiment, the Y group is selected from the group consisting of: GR, RG, KR, RK, K, R, M, and G. In one embodiment, the Y group is selected from the group consisting of: RG, KR, and K.

[0117] In one embodiment, the compound comprises only Y 2 Group, where Y 2 The group is selected from RG, KR and K.

[0118] Modified amino acids or unnatural amino acid analogs

[0119] In preferred embodiments, the pesticidal compound does not contain any modified amino acids or unnatural amino acid analogs.

[0120] Specifically, preferably, peptide Y 1 (if any) does not contain any modified amino acids or unnatural amino acid analogs, and peptide Y 2 (if any) does not contain any modified amino acids or non-natural amino acid analogs. Thus, in certain embodiments, peptide Y 1 and Y 2 Only unmodified amino acid residues are contained, suitably only naturally occurring amino acid residues.

[0121] In particular, peptide Z does not comprise any modified amino acids or non-natural amino acid analogs. Thus, in certain embodiments, peptide Z comprises only unmodified amino acid residues, suitably only natural amino acid residues.

[0122] active

[0123] Suitably, the compounds of the invention have anti-insect activity. Suitably, the activity is against insects of the order Hemiptera, Diptera, Lepidoptera, Blattodea and / or Coleoptera.

[0124] In preferred embodiments, the compounds of the invention have activity against lepidopteran insects. Therefore, the compounds of the invention may be particularly useful against lepidopteran insects and may be particularly useful in the related uses and methods described herein. Particularly preferred lepidopteran insects are moths.

[0125] The compounds of the invention generally increase insect mortality, for example when topically contacted with or ingested by suitable insects. Thus, the compounds of the invention described herein (and compositions containing them) can be considered insecticides, and can be referred to as "insect control agents."

[0126] Suitably, the compounds of the invention thereby indirectly increase plant health, including increasing plant growth, yield, etc., by preventing the plant from being infested by insects and reducing the insect load on the plant. Thus, the compounds of the invention described herein (and compositions containing them) may also be considered "plant protection agents".

[0127] Without wishing to be bound by theory, any or all of the effects described may be mediated by agonist activity at the pyrokinin receptors of the target insect. Pyrokinin receptors believed to be present in the target insect include the GPCR pyrokinin receptor 1 and pyrokinin receptor 2, PK1-R and PK2-R. The compounds of the present invention are suitable for binding to one or more pyrokinin receptors of the target insect. Suitably, the compounds of the present invention have agonist activity when binding to the pyrokinin receptors of the target insect. Suitably, the compounds of the present invention bind to pyrokinin receptor 1 and / or pyrokinin receptor 2. Suitably, the compounds of the present invention are agonists of pyrokinin receptor 1 and / or pyrokinin receptor 2.

[0128] Insect Control Agents

[0129] The term "insect control agent" refers to an agent used to increase the mortality of insects (i.e., as an insecticide). Any compound of the present invention or its composition can be considered an insect control agent and can be used as an insect control agent. Therefore, the present invention suitably provides the use of the compound or composition of the present invention as an insect control agent, for example, for Diptera, Hemiptera, Coleoptera, Blattodea and / or Lepidoptera. Therefore, an insect control agent can be applied to increase the mortality of a given insect or insect population.

[0130] As used herein, increased mortality refers to an increase in the percentage of dead insects compared to the percentage of dead insects in an otherwise identical insect population that has not been exposed to the insect control agents of the present invention.

[0131] Suitably, insect mortality can be calculated as the number of dead insects per treatment area / total number of insects. Suitably, the treatment area can be a well of a plate, or can be one or more leaves, or the entire plant. Suitably, insect mortality can be measured by carrying out an artificial diet assay for Lepidoptera as described in the Examples herein.

[0132] Insect control agents can be used to reduce the size of an insect population, or to inhibit the growth of an insect population, or to inhibit feeding by an insect population (eg, compared to an otherwise identical insect population not exposed to the agent).

[0133] An insect control composition is a composition comprising an insect control agent, ie, a compound of the present invention as described.

[0134] Plant protection agents

[0135] The term "plant protection agent" refers to an agent used to protect plants or plant parts from insects (e.g., to prevent infestation or colonization) or to be used as a food source by such insects (e.g., by draining juice). Any compound of the invention or its composition may be considered a plant protection agent and may be used as a plant protection agent. Thus suitably, the invention provides the use of a compound of the invention or a composition as a plant protection agent, for example, to protect plants from insects of the order Diptera, Hemiptera, Coleoptera, Blattodea and / or Lepidoptera.

[0136] Infestation or colonization may be by larvae (or nymphs), adults, or may be through use as a host or reservoir for eggs. However, the terms "infestation" and "colonization" should not be construed as requiring the presence of insects to be harmful to the plant.

[0137] Plant protection agents can be applied to reduce the insect load of plants or plant parts, inhibit or reduce insect infestation of plants, inhibit the increase of insect load of plants or plant parts (e.g., reduce its rate), or maintain plants in an insect-free state (compared to an otherwise identical plant with an insect population not exposed to the agent), among other purposes. Thus, plant protection agents can be applied to plants or plant parts that already carry Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects, or to plants or plant parts that are free or substantially free of Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects.

[0138] Crop protection compositions are compositions which comprise a crop protection agent, ie the compounds according to the invention as described.

[0139] plant

[0140] Reference herein to "plants or plant parts" or "plants or parts thereof" refers to any part of a plant, including but not limited to; leaves, stems, roots, flowers, buds, bulbs and seeds.

[0141] Suitable plants or parts thereof that can be protected by the compounds of the present invention or the compositions thereof or the agents of the present invention include crops and plants of agricultural, horticultural or economic importance. Suitable plants may include any of the following plants or parts thereof: abaca (Musa textilis), alfalfa (Medicago sativa), almonds (Prunus dulcis), anise (Pimpinella anisum), wild apple (Malus sylvestris), apricots (Prunus armeniaca), betel nut (Arecacatechu), root celery (Arracacia xanthorhiza), arrowroot (Maranta arundinacea), artichoke (Cynara scolymus), Jerusalem artichoke (Helianthus tuberosus), asparagus (Asparagus officinalis), avocado (Persea americona), American pennisetum (Pennisetum americanum), underground pea (Vigna subterranean), plantains (Musa paradisiaca), barley (Hordeum vulgare), beans (Phaseolus vulgaris), mung beans (Phaseolus vigna spp.), sugar beets (Beta vulgaris, bergamot (Citrusbergamia), Rubus spp., pepper (Piper nigrum), black wattle (Acaciamearnsii), blueberry spp., Brazil nut (Bertholletia excelsa), breadfruit (Artocarpus altilis), broad bean (Vicia faba), cauliflower (Brassica oleracea botrytis), sorghum (Sorghum bicolor), Brussels sprouts (Brassica oleracea gemmifera), buckwheat (Fagopyrum esculentum), Brussels sprouts (Brassica oleracea capitate), turnips (Brassica rapa), Brassica spp.), cocoa (Theobroma cacao), melon (Cucumis melo), caraway (Carumcarvi), cardamom (Elettaria cardamomum), cardoon (Cynara cardunculus), carob (Ceratoniasiliqua), carrot (Daucus carota), cashew (Anacardium occidentale), cassava (Manihotesculenta), castor (Ricinus communis), cauliflower (Brassica oleracea botrytis), celery (Apium graveolens), chayote (Sechium edule), plum species (Prunus spp.), chestnut (Castanea sativa), chickpea (Cicer arietinum), chicory (Cichorium intybus), chicory (Cichorium intybus), pepper species (Capsicum spp.), cinnamon (Cinnamomum verum), lemongrass (Cymbopogon nardus), citron (Citrus medica), Citrus (Citrus veticulata), Clover species (Trifolium spp.), Clove (Syzygium aromaticum), Coconut (Cocos nucifera), Colocasia spp.; Yellow-fleshed taro species (Xanthosoma spp.), Coffee species (Coffee spp.), Cola spp., Brassica napus, Maize (Zea mays), Wild lettuce (Valerianella locusta), Cotton species (Gossypium spp.), Cowpea (Vigna unguiculate), Blueberry species (Vaccinium spp.), Lepidium sativum, Cucumis sativus, Ribes species (Ribes spp.), Sugar apple (Annona reticulata), Colocasia esculenta, Date palm (Phoenix dactylifera), Moringa oleifera, Phaseolus spp.), garlic (Allium sativum), onion (Allium cepa), pea (Pisum sativum), durum wheat (Triticum durum), yellow taro species (Xanthosoma spp.); taro species (Colocasia spp.), eggplant (Solanum melongena), chicory (Cichorium endivia), needle grass (Lygeum spartum), fennel (Foeniculum vulgare), fenugreek (Trigonella foenumgraecum), fig (Ficus carica), European filbert (Corylus avellane), giant hemp (Furcraea macrophylla), flax (Linum usitatissimum), New Zealand hemp (Phormium tenax), geranium species (Pelargonium spp.); geranium species (Geranium spp.), ginger (Zingiber officinalis), gourd species (Langenaria spp.); pumpkin species (Cucurbita spp.), chickpeas (Cicer arietinum), grapefruit (Citrus paradise), grapes (Vitis vinifera), needle grass (Lygeum spartum), orchard grass (Dactylis glomerata), peanuts (Arachis hypogaea), guava (Psidium guajava), hazelnuts (Corylus avellane), Indian hemp (Crotalaria juncea), agave (Agave fourcroydes), henna (Lawsonia inermis), hops (Humulus lupulus), horseradish (Armoracia Rusticana), indigofera tinctorial, jasmine species (Jasminum spp.), jute species (Corchorus spp.), kale (Brassica oleracea acephala), kapok (Ceiba pentandra), kenaf (Hibiscus cannabinus), kohlrabi (Brassica oleracea gongylodes), Lavandula spp.), leek (Allium ampeloprasum), lemon (Citrus limon), lemongrass (Cymbopogon citratus), lentil (Lens culinaris), Lespedeza spp., lettuce (Lactuca sativa), liquorice (Glycyrrhiza glabra), lime (Citrus aurantifolia), mandarin (Citrus limetta), flax (Linum usitatissimum), litchi (Litchi chinensis), loquat (Eriobotrya japonica), lupin species (Lupinus spp.), macadamia species (Macadamia spp.), nutmeg (Myristica fragrans), agave (Agaveatrovirens), citrus (Citrus reticulata), mango (Mangifera indica), cassava (Manihotesculenta), rye (Secale cereal), hawthorn (Mespilus germanica), Cucumis melo, Penicum miliaceum, Eleusine coracana, Setaria italica, Echinochloa crusgalli, Eleusine coracana; Mentha spp., Morus spp., Morus alba, Agaricus spp.; Pleurotus spp., Volvariella, Brassica nigra; Sinapis alba, Prunus persica, Phormium tenax, Guizotia abyssinica, Myristica fragrans, Avena spp., Elaeis guineensis, Abelmoschus esculentus), olive (Olea europea), sweet orange (Citrus sinensis), sour orange (Citrus aurantium), orchard grass (Dactylis glomerate), sago palm species (Metroxylon spp.), Borassus flabellifer, Carica papaya, Pastinaca sativa, Pear, Pisum sativum, Carya illinoensis, Capsicum annuum, Diospyros kaki, Diospyros virginiana, Cajanus cajan, Ananas comosus, Pistacia spp., Prunus domestica, Punica granatum, Citrus grandis, Solamum tuberosum, Ipomoea batatas, Cucurbita spp., Chrysanthemum cineraraiefolium, Aspidosperma spp.), quince (Cydonia oblonga), cinchona species (Cinchona spp.), quinoa (Chenopodium quinoa), radish (Raphanus sativus) (including horseradish (Cochlearia armoracia)), ramie (Boehmeria nivea), bentgrass species (Agrostis spp.), ramie (Boehmeria nivea), rhubarb species (Rheum spp.), rice (Oryza sativa); Oryza glaberrima, rose species (Rose spp.), Brazilian rubber tree (Hevea brasiliensis), rye (Secale cereal), ryegrass species (Lolium spp.), safflower (Carthamus tinctorius), sago palm species (Metroxylon spp.), Onobrychis viciifolia, Wild lettuce (Valerianella locusta), Tragopogon porrifolius, Sapodilla (Achrassapota), Citrus (Citrus reticulata), Brussels sprouts (Brassica ileracea capitate), Black salsify (Scorzonera hispanica), Sesame (Sesamumindicum), Avocado (Butyrospermumparadoxum), Agave sislana, Lime (Citrus aurantifolia), Soybean (Glycinemax), Spelt (Triticum spelta), Spinach (Spinacia oleracea), Rye (Secalecereal), Cucurbita spp., Fragaria spp., Sudan grass (Sorghumbicolor Sudanense), Sugarcane (Saccharum officinarum), Sunflower (Helianthus annuus), Crotalaria juncea, lemon (Citrus limetta), sweet potato (Ipomoea batatas), citrus (Citrus reticulata), arrow-leaved yellow taro (Xanthosoma sagittifolium), cassava (Manihot esculenta), taro (Colocasia esculenta), tea tree (Camellia sinensis), Ethiopian teff (Eragrostisabyssinica), cattail (Phleum pratense), tobacco (Nicotiana tabacum), tomato (Lycopersicumesculentum), lotus species (Lotus spp.), stone chestnut species (Aleurites spp.), turnip (Brassicarapa), ground peach (Urena lobate), vanilla (Vanilla planifolia), bean (Vicia sativa), walnut species (Juglans spp.), watermelon (Citrullus lanatus), Acacia mearnsii, Triticum spp., Hordeum spp., Dioscorea spp.), Paraguayan tea (Ilex paraguariensis). .

[0142] Suitably, the plant or part thereof that can be protected by the compounds, compositions or agents of the present invention is selected from plants or parts thereof that are infested by Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera, or plants or parts thereof that attract Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera. Suitably, the plant or part thereof that is infested by Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera, or the plant or part thereof that attracts Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera is any of the above.

[0143] Suitably, the plant or part thereof which is infested by or attracts Hemipteran insects is any of those listed above.

[0144] Suitably, the plant or part thereof which is infested by or attracts dipteran insects is any of those listed above.

[0145] Suitably, the plant or part thereof which is infested by or attracts lepidopteran insects is any of those listed above.

[0146] Suitably, the plant or part thereof which is infested by or attracts coleopteran insects is any of those listed above.

[0147] Suitably, the plant or part thereof which is infested by or attracts Blattaria insects is any of those listed above.

[0148] In one embodiment, the plant or part thereof is selected from plants or parts thereof that are subject to or attract infestation by Hemiptera insects, for example: cereal crops, such as wheat (Triticum spp.), oats (Avena spp.), rye (Secale spp.), barley (Hordeum spp.), rice (Oryza spp.) and corn (Zea mays); fruit and vegetable crops, including apples (Malus spp.); pears (Plough spp.); strawberries (Fragaria spp.), blueberries (Vaccinium spp.), blackberries (Rubus spp.), raspberries (Rubus spp.), citrus (Citrus spp.), olives (Olea spp.), durian (Durio spp.), longan (Dimocarpus spp.), spp.), litchi (L. chinensis), persimmon (Diospyros spp.); beans and peas (including but not limited to species of bean, cowpea, pea, lablab, soybean, garbanzo, pigeon pea, and peanut), sugar beet (Beta vulgaris), sugarcane (Saccharum spp.), lettuce (Lactuca spp.), Brassica spp. (including rapeseed), onion (Allium spp.), tomato (Solanum spp.), pepper (Capsicum spp.), asparagus (Asparagus), melons, pumpkin, zucchini (Cucumis spp.), and tuber (potato) (Solanum spp.), or parts thereof.

[0149] In one embodiment, the plant or part thereof is selected from plants or parts thereof that suffer from or attract aphid infestation (suitably, green peach aphid infestation), including Solanaceae, Cruciferae, and Leguminosae, for example: cereal crops, such as wheat (Triticum species, including winter wheat); fruit and vegetable crops, including peach (Prunus species), strawberry (Fragaria species), blueberry (Vaccinium species), blackberry (Rubus species), raspberry (Rubus species), Brassica (Brassica species) (e.g. rapeseed), lettuce (Lactuca species), tomato (Solanum species), pepper (Capsicum species), beans and peas (including but not limited to Vigna, Pisum species), melons, pumpkin, zucchini (Cucumis species), citrus (Citrus species), and tubers (potato) (Solanum species), or parts thereof. In one embodiment, the plant is a vegetable crop, suitably a Brassica species.

[0150] In one embodiment, the plant or part thereof is selected from plants or parts thereof that are subject to or attract dipteran insect infestation, such as: cereals (Triticum species); oats (Avena species); rye (Secale species); barley (Hordeum species), rice (Oryza species) and corn (Zea mays species); beans and peas (including but not limited to Phaseolus, Vigna, Pisum, Lens, Glycine, Cicer, Cajanus, Arachis, etc.); fruit crops (including apples (Malus species), pears (Pyrus species), strawberries (Fragaria species), and peas (including but not limited to Phaseolus, Vigna, Pisum, Lens, Glycine, Cicer, Cajanus, Arachis, etc.); species), blueberry (Vaccinium species), blackberry (Rubus species), raspberry (Rubus species), cherry, plum, apricot, peach, nectarine (Prunus species), black currant, red currant, white currant, gooseberry (Ribes species), kiwifruit (Actinidia species), papaya (Carica papaya species), avocado (Persea gratis species), mango (Mangosteen), longan (Dimocarpus species), lychee (L. chinensis), grape (Vitis species), fig (Ficus species), passion fruit (Passiflora species), Asian pear (Pyrus species), citrus (Citrus species), and olives (Olea europaea species); vegetable crops, including Allium species (Allium spp.), eggplant, tomato (Solanum spp.) and peppers (Capsicum spp.), lettuce (Lactuca spp.), Brassica spp. and courgettes, cucurbits, pumpkin, courgette (Cucumber spp.); root crops of the Apiaceae family, including carrots (Daucus spp.), parsnips (Pastinaca spp.) or parts thereof.

[0151] In one embodiment, the plant or part thereof is selected from plants or parts thereof that are subject to or attract infestation by Lepidoptera insects, for example: cereal crops, such as wheat (Triticum species), oats (Avena species), rye (Secale species), barley (Hordeum species), rice (Oryza species) and corn (Zea mays); fruit and vegetable crops, including apples (Malus species); pears (Pyrus species); tree nuts (including, for example, almonds (Apricot kernels (P. amygdalus)), pistachios (Pistachios ), walnuts (Juglandaceae), hazelnuts (Corylus species); avocados, including alligator (Lauraceae), blueberries (Vaccinium species), citrus (Citrus species), olives (Olea species), durian (Durian species), longan (Diospyros species), litchi (L. chinensis), persimmon (Diospyros species); beans and peas (including but not limited to Phaseolus, Vigna, Pisum, Lablab, Glycine max, Garbanzo pea, Pigeon pea, Arachis species), sugar beets (sugar beet) (Beta vulgaris), sugar cane (Saccharum spp.), lettuce (Lactuca spp.), Brassica (Brassica spp.) (including rapeseed), onion (Allium spp.), tomato (Solanum spp.), pepper (Capsicum spp.), asparagus (Asparagus spp.), melons, pumpkin, zucchini (Cucumis spp.), and tuber (potato) (Solanum spp.), cauliflower (Brassica oleracea Botrytis), or parts thereof.

[0152] insect

[0153] The compounds, compositions and agents of the present invention suitably have anti-insect activity as described above.

[0154] The compounds, compositions and agents of the present invention are effective against any insect. For example, from the phylum Arthropoda, in particular from the class Arachnida, for example Acarus spp., Aceria sheldoni, Aculops spp., Aculus spp., Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides pteronyssius, Dermatophagoides farinae. farinae), Dermacentor spp., Eotetranychus spp., Epitrimerus pyri, Eutetranychus spp., Eriophyes spp., Halotydeus destructor, Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp., Metatetranychus spp., Nuphersa spp., Oligonychus spp., Ornithodorus spp.), Ornithonyssus spp., Panonychus spp., Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp.), Israeli killer scorpion (Scorpio maurus), narrow tarsonemus species (Stenotarsonemus spp.), Tarsonemus species (Tarsonemus spp.), Tetranychus species (Tetranychus spp.), Vaejovis species (Vaejovis spp.), tomato long-legged fly (Vasates lycopersici). .

[0155] Still other examples are from the order of the Anoplura (Phthiraptera), e.g., Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Ptirus pubis, Trichodectes spp.

[0156] There are other examples from the subclass Chilopoda, such as Geophilus spp., Scutigera spp.

[0157] Still other examples are from the order Coleoptera, for example Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Agelasta alni, Agriotes spp., Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus spp., Apion spp., Apogonia spp., Atomaria spp., Attagenus spp., Bruchidius obtectus), Bruchus spp., Cassida spp., Cerotoma trifurcata, Ceutorrhynchus spp., Chaetocnema spp., Cleonus mendicus, Conoderus spp., Cosmopolites spp., Costelytra zealandica, Ctenicera spp., Curculio spp., Cryptorhynchus lapathi, Cylindrocopturus spp., Dermestes spp., Diabrotica spp., Dichocrocis spp.), Diloboderus spp., Epilachna spp., Epitrix spp., Faustinus spp., Gibbium psylloides, Hellula undalis, Heteronychusarator, Heteronyx spp.), Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypothenemus spp., Lachnosterna consanguinea, Lema spp., Leptinotarsa ​​decemlineata, Leucoptera spp., Lissorhoptrus oryzophilus, Lixus spp., Luperodes spp., Lyctus spp., Megascelis spp., Melanotus spp., Meligethes aeneus), Melolontha spp., Migdolus spp., Monochamus spp., Naupactus xanthographus, Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus spp., Oxycetonia jucunda, Phaedoncochleariae, Phyllophaga spp., Phyllotreta spp., Popillia japonica, Premnotrypes spp., Prostephanus truncatus), Psylliodes spp., Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp., Sphenophorus spp., Stegobium paniceum, Sternechus spp., Symphyletes spp.), Tanymecus spp., Tenebrio molitor, Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp. Suitably, the compounds, compositions and agents of the invention have activity against a species of the order Coleoptera selected from, for example, the following: picture beetle (Eupatoria vulgaris), cabbage seed weevil (Ceutorhynchus obstrictus), cabbage stem flea beetle (Psylliodeschrysocephalus), cabbage stem weevil (Ceutorhynchus pallidactylus), scarab larvae (Melolontha melolontha), Colorado potato beetle (Leptinotarsa ​​decemlineata), pea and bean weevils (Sitona lineatus), pollen beetles (Meligethes spp.), dwarf beetles (Atomaria linearis), rape winter stem weevils (Ceutorhynchus picitarsis), and nematodes (Agriotes spp.).

[0158] There are other examples from the order Collembola, such as Onychiurus armatus.

[0159] There are other examples from the class Diplopoda, such as Blaniulus guttulatus.

[0160] Still other examples are from the order Diptera, for example Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Asphondylia spp., Bactrocera spp., Bibio hortulanus, Calliphora erythrocephala, Ceratitis capitata, Chironomus spp., Chrysomyia spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Cordylobia anthropophaga, Culex species. spp.), Culicoides spp., Culiseta spp., Cuterebra spp., Dacus oleae, Dasyneura spp., Delia spp., Dermatobia hominis, Drosophila spp., Echinocnemus spp., Fanniaspp., Gasterophilus spp., Glossina spp., Haematopota spp., Hydrellia spp., Hylemyia spp., Hyppobosca spp., Hypoderma spp.), Liriomyza spp., Lucilia spp., Lutzomia spp., Mansonia spp., Musca spp., Nezara spp., Oestrus spp., Oscinella frit, Pegomyia spp., Phlebotomus spp., Phorbia spp.), Phormia spp., Prodiplosis spp., Psila rosae, Rhagoletis spp., Sarcophaga spp., Simulium spp., Stomoxys spp., Tabanus spp., Tannia spp., Tetanops spp., Tipula spp. There are other examples of Heteroptera, such as Anasatristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylommalivida, Cavelerius spp., Cimex spp., Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp.), Eurygaster spp., Heliopeltis spp., Horcias nobilellus, Leptocorisa spp., Leptoglossus phyllopus, Lygus spp., Macropes excavatus, Miridae, Monalonion atratum, Nezaras spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., Psallus spp., Pseudacysta persea), Rhodnius spp.), Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp. Still other examples are from the order Homoptera, e.g., Acyrthosipon spp., Acrogonia spp., Aeneolamia spp., Agonascena spp., Aleurodes spp., Aleurolobus barodensis, Aleurothrixus spp., Amrasca spp., Anuraphis cardui, Aonidiella spp., Aphanostigma pin, Aphis spp., Arboridia apicalis, Aspidiella spp., Aspidiotus spp., Atanus spp.), Aulacorthum solani, Bemisia spp., Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae, Calligypona marginata, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chromaphis juglandicola, Chrysomphalus ficus), corn leafhopper (Cicadulinambila), gall aphid (Coccomytilus halli), waxworm species (Coccus spp.), Cryptomyzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina spp., Diaspis spp., Drosicha spp., Dysaphis spp., Dysmicoccus spp., Empoasca spp., Eriosoma spp., Erythroneura spp., Euscelis bilobatus, Ferrisia spp., Geococcus coffeae, Hieroglyphus spp.), Homalodiscacoagulata, Hyalopterus arundinis, Icerya spp., Idiocerus spp., Idioscopus spp., Laodelphaxstriatellus, Lecanium spp., Lepidosaphes spp., Lipaphis erysimi, Macrosiphum spp., Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metopolophium dirhodum, Monellia costalis), walnut flat-horned aphid (Monelliopsis pecanis), Myzus spp., stone fruit black aphid (Nasonovia ribisnigri), black leafhopper spp. (Nephotettix spp.), brown planthopper (Nilaparvata lugens), oncometopia spp., long-horned aphid (Orthezia praelonga), whitefly (Parabemisia myricae), wood aphid spp. (Paratrioza spp.), shield scale spp. (Parlatoria spp.), gall aphid spp. (Pemphigus spp.), Peregrinus maidis, Phenacoccus spp., Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp., Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus spp., Quesada gigas), Rastrococcus spp., Rhopalosiphum spp., Saissetia spp., Scaphoides titanus, Schizaphis graminum, Selenaspidus articulatus, Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina, Tenalaphara malayensis, Tinocallis caryaefoliae, Tomaspis spp., Toxoptera spp., Trialeurodes spp., Trioza spp.), Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.

[0161] Still other examples are from the order Hymenoptera, e.g. Acromyrmex spp., Athalia spp., Atta spp., Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Solenopsis invicta, Tapinoma spp., Vespa spp.

[0162] Still other examples are from the order Isopoda, e.g. Armadillidium vulgare, Oniscus asellus, Porcellio scaber.

[0163] Still other examples are from the order Isoptera, e.g., Coptotermes spp., Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Microtermes obesi, Odontotermes spp., Reticulitermes spp.

[0164] Still other examples are from the order Lepidoptera, for example Acronicta major, Adoxophyes spp., Aedia leucomelas, Agrotis spp., Alabama spp., Amyelois transitella, Anarsia spp., Anticarsia spp., Argyroploces spp., Barathra brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp., Caloptilia theivora), Capuareticulana, Carpocapsa pomonella, Carposina niponensis, Chematobia brumata, Chilo spp., Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnephasia spp., Conopomorpha spp., Conotrachelus spp., Copitarsia spp., Cydia spp., Dalaca noctuides, Diatraea saccharalis, Earias spp. spp.), Ecdytolopha aurantium, Elasmopalpuslignosellus, Eldana saccharina, Ephestia spp., Epinotia spp., Epiphyas postvittana, Etiella spp., Eulia spp.), Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp., Hedylepta spp., Helicoverpa spp., Heliothis spp., Hofmannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, Kakivoria flavofasciata, Laphygma spp., Laspeyresia molesta), Leucinodes orbonalis, Leucoptera spp., Lithocolletis spp., Lithophaneantennata, Lobesia spp., Loxagrotis albicosta, Lymantria spp., Lyonetia spp., Malacosomaneustria, Maruca testulalis, Mamestra brassicae, Mods spp., Mythimna separata, Nymphula spp., Oiketicus spp., Oria spp., Orthaga spp.), Ostrinia spp., Oulema oryzae, Panolis flammea, Parnara spp., Pectinophora spp., Perileucoptera spp., Phthorimaea spp.), Citrus leafminer (Phyllocnistiscitrella), Phyllonorycter spp., Pieris spp., Platynota stultana, Plodia interpunctella, Plusia spp., Plutella xylostella, Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., Pseudoplusia includens, Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., Scirpophaga spp., Scotia segetum), Sesamia spp., Sparganothis spp., Spodoptera spp., Stathmopodaspp., Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thermesia gemmatalis, Tineapellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp., Tutaabsoluta, Virachola spp.

[0165] Still other examples are from the order Orthoptera, e.g., Acheta domesticus, Dichroplus spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Melanoplus spp., Pulex irritans, Schistocerca gregaria.

[0166] Still other examples are from the order Blattaria, for example, Blatta orientalis, Blattella germanica, Periplaneta america, Periplaneta spp., Supella longipalpa, termites of the suborder Isoptera, such as those of the family Termitidae.

[0167] Still other examples are from the order of the Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp., Tunga penetrans, Xenopsyllacheopis.

[0168] There are other examples from orders within the phylum Syntagma, such as Scutigerella spp.

[0169] Still other examples are from the order Thysanoptera, for example Anaphothrips obscurus, Baliothrips biformis, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp., Heliothrips spp., Hercinothrips femoralis, Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp. Still other examples are from the order Thysanoptera (=Thysanura), for example Lepisma saccharina, Thermobia domestica.

[0170] In a preferred embodiment, the compounds, compositions and agents of the present invention suitably have activity against Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera. In a preferred embodiment, the compounds, compositions and agents of the present invention suitably have activity against Lepidoptera. In a preferred embodiment, the compounds, compositions and agents of the present invention suitably have activity against moths. In one embodiment, the compounds, compositions and agents of the present invention suitably have activity against the moth species Plutella xylostella. In one embodiment, the compounds, compositions and agents of the present invention suitably have activity against the moth species Spodoptera frugiperda. In one embodiment, the compounds, compositions and agents of the present invention suitably have activity against the moth / looper species Trichoplusia ni.

[0171] Hemiptera

[0172] The compounds, compositions and agents of the invention are suitably active against insects of the order Hemiptera, including aphids, plant hoppers, leafhoppers, stink bugs, shield bugs and cicadas. Suitably, the compounds, compositions and agents of the invention are suitably active against aphids.

[0173] Hemiptera are defined by having distinctive mouthparts in the form of a "beak", consisting of modified mandibles and maxillae forming a "stylet" which fits within a modified labrum.

[0174] Many insects within these groups have endogenous neuropeptides with sequence homology to the peptides described herein, suggesting that the compounds of the invention may be active against these insects.

[0175] These insects may belong to the suborder Sternorhynchoidea, for example to the superfamily Aphidoidea (aphids), Aleyroidea (whiteflies), Coccidioidea (scale insects), Phylloxera (including the Phylloxera family or "root nodule aphids", and Aphididae or hairy conifer aphids), or Psyllidoidea (jumping plant lice, etc.).

[0176] Thus, the insect may be an aphid, a member of the aphid superfamily (Aphidoidea). Aphids (Hemiptera: Aphididae) are one of the most important groups of agricultural pests and are vectors for about 50% of insect-borne plant viruses. Within this superfamily, aphids may be part of the Aphididae family, which contains the following subfamilies: Aiceoninae, Anoeciinae, Aphidinae, Baltichaitophorinae, Calaphidinae, Chaitophorinae, Drepanosiphinae, Eriosomatinae, Greenideinae, Hormaphidinae, Israeliaphidinae, Macroideinae The subfamily includes the following: Lachninae, Lizeriinae, Macropodaphidinae, Mindarinae, Neophyllaphidinae, Phloeomyzinae, Phyllaphidinae, Pterastheniinae, Saltusaphidinae, Spicaphidinae, Taiwanaphidinae, Tamaliinae, and Thelaxinae.

[0177] The aphids may, for example, belong to the genus Aphis (e.g. Aphis pea), Aphis (e.g. Aphis gossypii, Aphis glycines, Aphis fabae), Diuraphis (e.g. Diuraphis noxia), Macrosiphum (e.g. Aphis rosea, Aphis potatoaphid), Aphis (e.g. Myzus persicae), Aphis (e.g. Aphis cerealis), or Aphis (e.g. Aphis wheataphid).

[0178] Green peach aphid (Myzus persicae) is the most economically important aphid crop pest worldwide, with a global distribution and a host range of more than 400 species in 40 different plant families. For example, it is a major pest of crops including fruit and potato, and a vector of viruses.

[0179] Macrosiphon rosea (Rose aphid) is an important horticultural pest, especially of cultivated roses, and is a vector of 12 plant viruses, including strawberry mild yellow edge virus.

[0180] Cotton aphid (cotton aphid or cucurbit aphid) is a pest of cucurbits and cotton.

[0181] In addition to aphids, the insects may, for example, belong to the family Aphididae, such as the genus Aphid (eg Aphid).

[0182] These insects may belong to the family Aleyrodidae, such as the genus Trialeurodes (eg Bemisia tabaci) or Trialeurodes (eg Trialeurodes).

[0183] These insects may belong to the family Psyllidae, such as the genus Pachypsylla (eg Pachypsylla venusta).

[0184] As examples of Hemiptera outside the suborder Thoracophoridae, these insects may belong to the family Cimicifuga, for example to the genus Cimicifuga (bed bugs), such as Cimex lectularius.

[0185] These insects may belong to the family Cicadidae, such as the genus Cuerna (e.g., Cuerna arida), the family Poaceae (e.g., Graminella nigrifrons), or the genus Homalodisca (e.g., Homalodisca vitripennis). The family Cicadidae also includes the cotton leafhopper (Amrasca biguttula).

[0186] These insects may belong to the family Delphacidae, such as the genus Nilaparvata (e.g. brown planthopper) or the genus Sogatella (e.g. white-backed planthopper). For example, the brown planthopper (brown planthopper) is a pest of rice crops, especially in Asia.

[0187] These insects may belong to the family Psyllidae, for example to the genus Psyllid (eg, the citrus psyllid).

[0188] These insects may belong to the family of the Lygus family, for example the genus Pseudatomoscelis (e.g. Lygus hesperus), the genus Lygus (e.g. Lygus hesperus) or Tupiocoris (e.g. Tupiocoris notatus). For example Lygus hesperus (cotton flea) is a pest of cotton.

[0189] These insects may belong to the family Pentatomidae, such as Euschistus (e.g., Euschistus servus), Banasa (e.g., Banasa dimiata), Euschistus (e.g., Euschistus heroes), Euschistus (e.g., Euschistus servus), Euschistus heroes), Euschistus (e.g., Euschistus strionica), Euschistus (e.g., Murgantia histrionica), Euryale (e.g., Euryale oryzae), Euschistus (e.g., Euryale oryzae), Euschistus (e.g., Euryale oryzae), or Euschistus (e.g., Euschistus strionica). For example, Euschistus servus (green stink bug) is an important pest of cotton. Euschistus servus (brown stink bug) is a pest of many agricultural crops, including seeds, grains, nuts, and fruits, especially in the southern United States. Euschistus servus is a pest of grain and soybean crops, especially in Brazil.

[0190] These insects may be of the family Pyrrocoris, for example of the genus Pyrrocoris (eg Pyrrocoris apterus).

[0191] These insects may belong to the family Assassinidae, for example to the genus Rhodnius (eg Rhodnius prolixus), or the genus Triatoma (eg Triatoma infestans). Rhodnius prolixus is a vector of human disease (Chagas disease).

[0192] These insects may belong to a family of psyllids, such as Acanthocasuarina muellerianae.

[0193] In one embodiment, the insect can be selected from the following species: A. hilare, ...

[0194] In one embodiment, the insect is of the species Myzus persicae.

[0195] Diptera

[0196] The compounds, compositions and agents of the invention may be active against insects of the order Diptera.

[0197] In particular, they may be active against Drosophilidae, such as fruit flies, including Drosophila, such as Drosophila suzukii. They may also be active against Tephritis, including Anastrepha (Anastrepha species); Bactrocera (Bactrocera species); Bactrocera (Bactrocera species); Tephritis (Tephritis spp.); Tephritis (Tephritis spp.).

[0198] Drosophilidae and Tephritidae are often collectively referred to as fruit flies.

[0199] The compounds, compositions and agents may also be active against other important dipteran pests, such as flies of the family Physiophidae (blow flies) and flies of the genera:

[0200] Phytominers (e.g. Phytomyza angelicastri);

[0201] Melani (e.g. Melani agromyza);

[0202] Antherigona (e.g. Antherigona species);

[0203] Ground fly (e.g., Delia radicum);

[0204] Contarinia (e.g. Contarinia sorghicola);

[0205] For more details on these and other examples, see Developing the Arsenal Against Pest and Vector Dipterans: Inputs of Transgenic and Paratransgenic Biotechnologies, Ogaugwu and Durvasula, IntechOpen, 2017: DOI: 10.5772 / 66440

[0206] Lepidoptera

[0207] The compounds, compositions and agents of the invention may be active against insects of the order Lepidoptera.

[0208] In particular, they may be active against insects of the genera Heliothis, Plutella, Spodoptera, Cydia and Trichoplusia. Suitably, the compounds, compositions and agents of the invention may be active against Heliothis, H. virescens, Spodoptera species, and Cydia pomonella (apple moth), larvae of Heliothis species, including Peltigera virescens and Spodoptera littoralis (which represent a variety of Heliothis and Spodoptera moth species and are worldwide agricultural pests), Plutella xylostella (diamondback borer, the most important Brassica pest worldwide), and Trichoplusia ni (cabbage looper).

[0209] In one embodiment, the compounds, compositions and agents of the present invention may have activity against Plutella xylostella. In one embodiment, the compounds, compositions and agents of the present invention may have activity against Spodoptera frugiperda. In one embodiment, the compounds, compositions and agents of the present invention may have activity against Trichoplusia ni.

[0210] Coleoptera

[0211] The compounds, compositions and agents of the invention may be active against insects of the order Coleopteran.

[0212] In particular, they may be active against insects of the genera Bruchus, Ceutorhynchus, Psylliodes, Leptinotarsa, Sitona, Meligethes, Atomaria, and Agriotes. Suitably, the compounds, compositions and agents of the invention may be active against the following species: picture beetle (Vicia faba), cabbage seed weevil (Ceutorhynchus obstrictus), cabbage stem flea beetle (Psylliodes chrysocephalus), cabbage stem weevil (Ceutorhynchus pallidactylus), scarab larvae (Melolontha melolontha), Colorado potato beetle (Leptinotarsa ​​decemlineata), pea and bean weevils (Sitonalineatus), pollen beetles (Meligethes spp.), dwarf beetles (Atomaria linearis), rapeseed winter stem weevil (Ceutorhynchus picitarsis), and nematodes (Agriotes spp.)

[0213] Insects of the order Blattida

[0214] The compounds, compositions and agents of the invention may be active against insects of the order Blattodea.

[0215] In particular, they may be active against insects of the order Isoptera.Suitably, the compounds, compositions and agents of the invention may be active against species of the family Termitidae.

[0216] Suitably, the compounds, compositions and agents of the invention may be active against the following species: Blatta orientalis, Blattella germanica, Periplaneta americana, Periplaneta spp., Supella longipalpa.

[0217] Household pests

[0218] The compounds, compositions and agents of the present invention may also have activity against household pests, such as cockroaches and termites (e.g., termites of the family Termitidae). These may include, among more than 3000 species, German cockroaches (German cockroaches), Oriental cockroaches (Oriental cockroaches), American cockroaches (American cockroaches), and brown-banded cockroaches (Brown-banded roaches). Cockroaches are common household pests worldwide and may carry a variety of diseases. It is contemplated that these and other household pests (e.g., ants) may be controlled by treating surfaces where the insects run, but particularly with food baits containing the compounds, compositions and agents of the present invention, as well as direct spray applications of the compounds, compositions and agents of the present invention.

[0219] Therefore, other aspects of the present invention may include baits comprising the compounds or compositions of the present invention, which may be baits for household pests. Other aspects of the present invention may include methods for controlling household pests, reducing household pest populations, suppressing household pest populations, and increasing household pest mortality rates, the method comprising treating surfaces (e.g., wood) contacted by household pests with the compounds or compositions of the present invention, or contacting household pests with the compounds or compositions of the present invention. Further details of such methods are described below. Optionally, processing or contacting may include suitable modes of application as described elsewhere herein, such as by spraying. Therefore, sprayable formulations comprising the compounds or compositions of the present invention are also suitably envisioned. Suitable formulations are described elsewhere herein.

[0220] Methods and uses of the present invention

[0221] Ways to increase insect mortality

[0222] The present invention provides a method of increasing insect mortality, comprising contacting an insect or insect population with a compound, composition or combination as described herein. The insect or insect population can be a Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insect.

[0223] In one embodiment, there is provided a method of increasing mortality of a dipteran insect, the method comprising contacting a dipteran insect or a dipteran insect population with a compound or composition or combination of the present invention.

[0224] In a specific embodiment, a method of increasing mortality of Drosophila suzukii is provided, comprising contacting a Drosophila suzukii insect or insect population with a compound or composition or combination of the present invention.

[0225] In one embodiment there is provided a method of increasing mortality of a Hemipteran insect, the method comprising contacting a Hemipteran insect or a population of Hemipteran insects with a compound or composition or combination as defined herein.

[0226] In a particular embodiment, there is provided a method of increasing mortality of aphids, the method comprising contacting an aphid or insect population with a compound or composition or combination as defined herein.

[0227] In a specific embodiment, there is provided a method of increasing the mortality of beet aphid (Aphis fabae), cotton aphid (Aphis gossypii), pea aphid (Acyrthosiphon pisum), peach aphid (Myzus persicae), cotton leafhopper (Amrascabiguttula) or cereal aphid (Rhopalosiphum padi), the method comprising contacting the beet aphid, cotton aphid, pea aphid, peach aphid, cotton leafhopper, cereal aphid insect or insect population with a compound or composition or combination as defined herein.

[0228] In a particular embodiment, there is provided a method of increasing the mortality of green peach aphid, the method comprising contacting a green peach aphid insect or insect population with a compound or composition or combination as defined herein.

[0229] In a particular embodiment, there is provided a method of increasing mortality of aphid, comprising contacting a aphid insect or insect population with a compound or composition or combination as defined herein.

[0230] In one embodiment there is provided a method of increasing mortality of a lepidopteran insect, the method comprising contacting the lepidopteran insect or a population of lepidopteran insects with a compound or composition or combination as defined herein.

[0231] In a particular embodiment, there is provided a method of increasing mortality of Plutella xylostella, the method comprising contacting a Plutella xylostella insect or insect population with a compound or composition or combination as defined herein.

[0232] In a particular embodiment, there is provided a method of increasing mortality of Spodoptera frugiperda, the method comprising contacting a Spodoptera frugiperda insect or insect population with a compound or composition or combination as defined herein.

[0233] In a particular embodiment, there is provided a method of increasing mortality of Trichoplusia ni, the method comprising contacting a Trichoplusia ni insect or insect population with a compound or composition or combination as defined herein.

[0234] In one embodiment there is provided a method of increasing mortality of a coleopteran insect, the method comprising contacting the coleopteran insect or a population of coleopteran insects with a compound or composition or combination as defined herein.

[0235] In one embodiment there is provided a method of increasing mortality of Blattaria insects, the method comprising contacting the Blattaria insects or a population of Blattaria insects with a compound or composition or combination as defined herein.

[0236] Methods for inhibiting or reducing infestation of plants or loci

[0237] The present invention also provides a method of inhibiting infestation of plants or plant parts by insects, suitably insects of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera, the method comprising contacting the plants or plant parts with the compound, composition or combination described.

[0238] In one embodiment, there is provided a method of inhibiting infestation of plants by dipteran insects, the method comprising contacting the plants with a compound or composition or combination of the present invention.

[0239] In a specific embodiment, there is provided a method of inhibiting infestation of a plant by Drosophila suzukii, the method comprising contacting the plant with a compound or composition or combination of the present invention.

[0240] In one embodiment there is provided a method of inhibiting infestation of a plant by insects of the order Hemiptera, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0241] In one embodiment there is provided a method of inhibiting infestation of a plant by aphids, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0242] In one embodiment there is provided a method of inhibiting infestation of a plant by beet aphid, cotton aphid, pea aphid, peach aphid or cereal aphid, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0243] In a particular embodiment, there is provided a method of inhibiting infestation of a plant by R. graminearum, which method comprises contacting the plant with a compound or composition or combination as defined herein.

[0244] In one embodiment there is provided a method of inhibiting infestation of a plant by Myzus persicae, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0245] In one embodiment there is provided a method of inhibiting infestation of a plant by a brown winged stink bug, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0246] In one embodiment there is provided a method of inhibiting infestation of a plant by lepidopteran insects, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0247] In one embodiment there is provided a method of inhibiting infestation of a plant by Plutella xylostella, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0248] In one embodiment there is provided a method of inhibiting infestation of a plant by Spodoptera frugiperda, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0249] In one embodiment there is provided a method of inhibiting infestation of a plant by Trichoplusia ni, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0250] In one embodiment there is provided a method of inhibiting infestation of a plant by coleopteran insects, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0251] In one embodiment there is provided a method of inhibiting infestation of a plant by insects of the order Blattodea, the method comprising contacting the plant with a compound or composition or combination as defined herein.

[0252] The invention also provides a method of inhibiting infestation of a locus where plants are growing or expected to grow by insects, suitably of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera, the method comprising contacting the locus with a compound, composition or combination as described.

[0253] The method may be preventative. Thus, for example, the compound may be applied to a plant or plant part or locus at a time when the plant or plant part or field is free or substantially free of insects.

[0254] Suitably, the location may be any agricultural location suitable for growing plants. Suitably, the location may be any area or location suitable for plant growth or plant growth. Suitable locations may include farmland, brownfields, fields, greenhouses, conservatories, containers, aquaponics and hydroponic systems, etc. In one embodiment, the location is a field.

[0255] Alternatively, the plant or plant part or locus may have been colonized or infested by insects, suitably of the orders Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera.

[0256] Thus, the present invention also provides a method of reducing insect infestation of a plant or plant part, or reducing the insect load of a plant or plant part, the method comprising contacting the plant or plant part with a compound, composition or combination as described herein. The present invention also provides a method of reducing insect infestation of a field or reducing the insect load in a field, the method comprising contacting the field with a compound, composition or combination as described herein. Suitable are insects of the orders Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera.

[0257] Ways to reduce insect feeding

[0258] The present invention also provides a method of reducing insect feeding, the method comprising contacting an insect or insect population with a compound, composition or combination as described herein. Suitably, the insect feeding on a plant or plant part is reduced. The insect or insect population may be a Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insect.

[0259] Ways to Protect Plants from Insects

[0260] The present invention also provides a method for protecting plants or parts thereof from insects or from insect infestation, in particular a method for protecting plants or plant parts from insects of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera or infestation thereof, wherein the method comprises applying the insecticidal compound or composition or combination of the present invention directly or indirectly to the plant or plant part. Suitably indirect application may comprise applying the compound or composition or combination of the present invention to a field or place where the plant is growing or expected to grow.

[0261] The present invention also provides a post-harvest treatment method for protecting or treating harvested plants or harvested parts of plants against insects or insect infestations, particularly against Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera insects or their infestations, the method comprising applying the insecticidal compound or composition of the present invention or combination directly or indirectly to the harvested plants or harvested parts of plants under conditions that effectively protect or treat the harvested plants or harvested parts of plants against insects. Suitably, indirect application may include applying the compound of the present invention or composition or combination to the storage location of the plant or harvested parts of the plant, or the location where storage is expected.

[0262] Suitably, the insect may be of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera.

[0263] How to contact insects

[0264] In one embodiment, there is provided a method of contacting insects with a compound, preferably an insect control agent, even more preferably an insecticide, which comprises applying a compound or composition or combination of the present invention to or onto a locus frequented by insects.

[0265] The location frequented by insects may be the natural habitat of the insects, or a place where the insects are active. The location may then be treated with a compound or composition as described above: as a non-limiting example, a mosquito net impregnated with an encapsulated insecticide may be used as a method of application. Alternatively, the location is created by applying a visual bait or attractant for the insects. Visual baits are known to those skilled in the art and include, but are not limited to, light sources, colored objects, and shapes or outlines that stand out against a contrasting background. As described above, insect attractants include, but are not limited to, pheromones, kairomones, and egotropes. The attractant may be present in the composition, or may be applied separately from the compound or composition or combination to ensure that the insects are attracted to the location where the compound or composition or combination is applied.

[0266] Suitably, the insect may be of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera. More suitably, the insect belongs to the order Lepidoptera. Most suitably, the insect is a moth, such as Plutella xylostella or Spodoptera frugiperda or Trichoplusia ni.

[0267] Administration of compounds or compositions

[0268] The compound or composition or combination of the present invention can be contacted with insect or insect colony, and suitably, this can include applying the compound or composition or combination directly to insect or insect colony. For example, it can be applied topically. Alternatively, the compound or composition or combination can be applied indirectly. For example, it can be applied to a substrate, a place or a place that may be contacted with an insect or insect colony. The substrate can be a part of a plant or a plant, especially for a Hemiptera or a Diptera or a Coleoptera or a Lepidoptera or a Blattale representing a plant (whether it is a crop or a horticultural plant) harmful organism, or can be a field, a place or a region suitable for plant growth. Therefore, suitably, the compound or composition or combination can be applied to a plant or a plant part. Therefore, suitably, the compound or composition or combination can be applied to a place where a plant grows.

[0269] However, for insects that are harmful to humans, such as Cimicifuga (e.g., bed bugs of the genus Cimicifuga, such as Cimex lectularius) or Assassinidae (e.g., bed bugs of the genus Cimicifuga, such as Cimex lectularius), which can act as vectors of human disease, the substrate can be a household surface or article, such as bedding, a mattress, or any other suitable household surface. The compound or composition can be applied to the substrate in a form suitable for ingestion by the insect.

[0270] Suitable contacting may include, for example, feeding or spraying.Feeding may be suitably encouraged by a bait attractant, which may be included in the composition of the invention, as explained below.

[0271] These methods may include contacting or applying a compound or composition or combination disclosed herein directly or indirectly to a plant or a part of a plant, for example at an application rate of more than 5 g of compound per hectare, for example, but not limited to, an application rate of more than 10 g of compound per hectare, for example, an application rate of more than 24 g of compound per hectare, for example, an application rate of more than 50 g of compound per hectare, for example, an application rate of more than 75 g of compound per hectare, for example, an application rate of more than 100 g of compound per hectare, or in particular, an application rate of more than 200 g of compound per hectare. These methods may include applying a compound, composition or combination disclosed herein directly or indirectly to a plant or a part of a plant, for example, at an application rate of 5 to 100 g of compound composition or combination per hectare, for example, but not limited to, an application rate of 5 to 200 g of compound composition or combination per hectare, in particular, an application rate of 5 to 50 g of compound composition or combination per hectare, for example, 5 to 30 g of compound composition or combination per hectare, or 10 to 25 g per hectare.

[0272] Compounds or compositions or combinations disclosed herein can be sprayed, sprayed, foamed, sprayed with smoke, hydroponics, hydroponics, coating, immersion, injection and / or encrustation, optionally after harvest, directly or indirectly contacted with a plant or a part of a plant / applied to a plant or a part of a plant. Suitable contact may include, for example, feeding or spraying. In certain embodiments, contact is carried out by ingestion. Contact may include using a composition as defined herein using a system and method described in, for example, WO 2020 / 021041, WO 2023 / 161802, WO 2022 / 264053, WO 2022 / 189386, WO 2022 / 165248, WO 2021 / 152093, WO 2020 / 212612 and WO 2020 / 021041 (the entire contents of the document are incorporated herein by reference) to inject a plant (e.g., tree) or part thereof.

[0273] Suitably, the compound may be contacted with the insect or insect population, or plant or plant part at any suitable effective concentration. Suitably, the compositions and combinations may comprise such effective concentrations of the compound. Suitably, the concentration of the compound is between 10 -3 Up to 10 -9 M, preferably between 10 -4 Up to 10 -6 M, preferably between 10 -4 Up to 10 -5 Between M.

[0274] Used as plant protection agent

[0275] The invention further provides the use of a compound, composition or combination as described herein as a plant protection agent, in particular for protecting plants or plant parts against insects, suitably Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera. Plant protection agents are further described above.

[0276] Used as an insect control agent

[0277] The present invention provides the use of a compound or composition as described herein or a combination thereof as an insect control agent, in particular in a method of increasing insect mortality or in a method of inhibiting insect infestation of plants.

[0278] The invention also provides for use of a compound or composition as described herein or a combination thereof as an insect control agent, in particular for use in a method of increasing mortality of Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera insects, or for use in a method of inhibiting or reducing infestation by insects (suitably Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera insects), or reducing the insect load of a plant.

[0279] The present invention also provides the use of the compounds or compositions described herein or a combination thereof as insect control agents, in particular by virtue of their biostatic effect on Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera insects, their biocidal effect on Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera insects, and / or their pesticidal effect on Hemiptera, Diptera, Coleoptera, Blattaria and / or Lepidoptera insects.

[0280] As used herein, "biostatic (effect)" or "biostatic use" includes any effect or use of a compound or composition or combination as described herein (optionally contained in a biostatic, biocidal, fungicidal or fungistatic composition as defined herein) for controlling, regulating or interfering with the harmful activity of a pest (e.g., a plant pest or a plant pathogen). Suitably, the pest is an insect of the order Hemiptera, Diptera, Coleoptera, Blattodea and / or Lepidoptera. Suitably includes, but is not limited to, inhibiting the growth or activity of insects, altering the behavior of insects, and repelling or attracting insects in plants, plant parts or other agriculturally relevant environments, such as for domestic use or in the soil.

[0281] "Pesticide activity" or "biocidal activity" are used interchangeably herein and refer to killing or severely disabling a pest. Suitably, it may be the same as insecticide activity when the pest is an insect. Suitably, the compound, composition or combination may be used as an insect control agent, wherein the insect encodes a pyrokinin.

[0282] Suitably, the compound or composition or combination may be used as an insect control agent, wherein the insect is of the order Diptera. Suitably, the compound may be used as an insect control agent, wherein the insect belongs to the genus Drosophila. Suitably, the compound may be used as an insect control agent, wherein the insect is Drosophila suzukii.

[0283] Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is an aphid. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect belongs to the genus Myzus aphid. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is Myzus persicae.

[0284] Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is of the order Hemiptera. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect belongs to the genus Mylostomus. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is Mylostomus punctatus.

[0285] Suitably, the compounds or compositions or combinations defined herein may be used as insect control agents, wherein the insect belongs to the order Lepidoptera. Suitably, the compounds or compositions or combinations defined herein may be used as insect control agents, wherein the insect belongs to the genus Plutella xylostella. Suitably, the compounds or compositions or combinations defined herein may be used as insect control agents, wherein the insect is Plutella xylostella.

[0286] Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect belongs to the order Lepidoptera. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect belongs to the genus Spodoptera. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is Spodoptera frugiperda.

[0287] Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect belongs to the order Lepidoptera. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect belongs to the genus Trichoplusia ni. Suitably, the compounds or compositions or combinations as defined herein may be used as an insect control agent, wherein the insect is Trichoplusia ni.

[0288] Suitably, the compounds or compositions or combinations defined herein may be used as an insect control agent, wherein the insect belongs to the order Coleoptera.

[0289] Suitably, the compounds or compositions or combinations defined herein may be used as an insect control agent, wherein the insect belongs to the order Blattodea. Suitably, the compounds or compositions or combinations defined herein may be used as an insect control agent, wherein the insect is a cockroach or a termite.

[0290] Methods of controlling insect fertility

[0291] The present invention also provides insecticidal compounds, compositions and combinations as described herein for controlling the fertility of insect species. Suitably, the insect is selected from Hemiptera, Diptera, Coleoptera or Lepidoptera, such as those described anywhere herein. Suitably, wherein in some embodiments, the Hemiptera insect is Myzus persicae. Suitably, wherein in some embodiments, the Diptera insect is Drosophila suzukii. Suitably, wherein in some embodiments, the Lepidoptera insect is Plutella xylostella. Suitably, wherein in some embodiments, the Lepidoptera insect is Spodoptera frugiperda. Suitably, wherein in some embodiments, the Lepidoptera insect is Spodoptera frugiperda.

[0292] Also provided is a method of controlling the fertility of a Hemipteran insect, the method comprising contacting a compound of the invention or a composition of the invention with a substrate (eg a plant or soil). Suitably, the Hemipteran insect is any one disclosed herein, such as an aphid.

[0293] Also provided is a method of controlling the fertility of a dipteran insect, the method comprising contacting a compound of the invention or a composition of the invention with a substrate (eg a plant or soil). Suitably, the dipteran insect is any of those disclosed herein.

[0294] Also provided is a method of controlling fertility of a lepidopteran insect, the method comprising contacting a compound of the invention or a composition of the invention with a substrate (eg a plant or soil). Suitably, the lepidopteran insect is any of those disclosed herein.

[0295] Also provided is a method of controlling the fertility of a coleopteran insect, the method comprising contacting a compound of the invention or a composition of the invention with a substrate (eg a plant or soil). Suitably, the coleopteran insect is any of those disclosed herein.

[0296] Also provided is a method of controlling the fertility of a Blattodea insect, the method comprising contacting a compound of the invention or a composition of the invention with a substrate (eg a plant or soil). Suitably, the Blattodea insect is any of those disclosed herein.

[0297] Also provided is a method of controlling the fertility of a hemipteran insect, the method comprising contacting a combination as described herein with a substrate, such as a plant or soil. Suitably, the hemipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0298] Also provided is a method of controlling the fertility of a dipteran insect, the method comprising contacting a combination as described herein with a substrate, such as a plant or soil. Suitably, the dipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0299] Also provided is a method of controlling fertility of lepidopteran insects, the method comprising contacting a combination as described herein or a composition of the invention with a substrate (e.g., a plant or soil). Suitably, the lepidopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or its analog.

[0300] Also provided is a method of controlling the fertility of coleopteran insects, the method comprising contacting a combination as described herein or a composition of the invention with a substrate (e.g., a plant or soil). Suitably, the coleopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or its analog.

[0301] Also provided is a method of controlling Blattaria fertility, the method comprising contacting a combination as described herein or a composition of the invention with a substrate (e.g., a plant or soil). Suitably, the Blattaria insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0302] Also provided is a method of controlling the fertility of a Hemipteran insect or insect population, the method comprising contacting a compound of the invention or a composition of the invention with a Hemipteran insect or insect population. Suitably, the Hemipteran insect is any of those disclosed herein.

[0303] Also provided is a method of controlling the fertility of a dipteran insect or insect population, the method comprising contacting a compound of the invention or a composition of the invention with a dipteran insect or insect population. Suitably, the dipteran insect is any of those disclosed herein.

[0304] Also provided is a method of controlling the fertility of a lepidopteran insect or insect population, the method comprising contacting a compound of the invention or a composition of the invention with a lepidopteran insect or insect population. Suitably, the lepidopteran insect is any of those disclosed herein.

[0305] Also provided is a method of controlling the fertility of a coleopteran insect or insect population, the method comprising contacting a compound of the invention or a composition of the invention with a coleopteran insect or insect population. Suitably, the coleopteran insect is any of those disclosed herein.

[0306] Also provided is a method of controlling the fertility of an insect of the order Blattaria or an insect population, the method comprising contacting an insect of the order Blattaria or an insect population with a compound of the invention or a composition of the invention. Suitably, the insect of the order Blattaria is any of those disclosed herein.

[0307] Also provided is a method of controlling the fertility of a Hemipteran insect or insect colony, the method comprising contacting a Hemipteran insect or insect colony with a combination as described herein. Suitably, the Hemipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0308] Also provided is a method of controlling the fertility of a dipteran insect or insect colony, the method comprising contacting a combination as described herein with a dipteran insect or insect colony. Suitably, the dipteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0309] Also provided is a method of controlling the fertility of a lepidopteran insect or insect colony, the method comprising contacting a combination as described herein or a composition of the invention with a lepidopteran insect or insect colony. Suitably, the lepidopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0310] Also provided is a method of controlling the fertility of a coleopteran insect or insect colony, the method comprising contacting a combination as described herein or a composition of the invention with a coleopteran insect or insect colony. Suitably, the coleopteran insect is any of those disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0311] Also provided is a method of controlling the fertility of a Blattaria insect or insect colony, the method comprising contacting a combination as described herein or a composition of the invention with a Blattaria insect or insect colony. Suitably, the Blattaria insect is any of those insects disclosed herein. Suitably, the combination comprises a compound of the invention and a kinin or an analog thereof.

[0312] In the context of the present invention, "controlling fertility" refers to reducing, inhibiting or eliminating the presence of an insect species during one or more of its growth stages. For example, the compositions of the present invention can be used to control the growth of mites at any stage (e.g., eggs, larvae, nymphs and adult forms).

[0313] Combination with other insecticides

[0314] The compounds of the invention may be used in combination with one or more additional pesticides or pesticidal compounds, such as those described herein. Also provided are combinations comprising a compound of the invention, or a salt or solvate thereof, in combination with one or more additional active pesticides or pesticidal compounds.

[0315] The compositions of the present invention may also contain one or more additional active pesticides or active pesticide compounds.

[0316] Suitably, the insecticide may be selected from an insect neuropeptide or an analog thereof, such as a kinin, an AKH peptide, a DH31 peptide, a DH44 peptide, a pyrokinin or a CAPA peptide (e.g., a CAPA-1, CAPA-2 or CAPA-3 analog). In a particular embodiment, the additional insecticide is a kinin, such as SB-P-69 ([Hy]-NFSPWG-[NH2], SEQ ID NO: 14). Additionally or alternatively, the insecticide may be selected from chemical insecticides, for example: pyrethroids (permethrin, cypermethrin, deltamethrin); organophosphates (malathion, chlorpyrifos, diazinon); neonicotinoids (imidacloprid, clothianidin, thiamethoxam); carbamates (carbaryl, methomyl, propoxur); botanical insecticides (pyrethrins (derived from chrysanthemums), rotenone (derived from certain plant roots)); biopesticides (Bacillus thuringiensis (Bt) products, Beauveria bassiana (fungus), Metarhizium anisopliae (fungus)); insect growth regulators (IGRs) (methoprene, pyriproxyfen); fipronil; spinosad; avermectins (including avermectin and ivermectin); chitin synthesis inhibitors (diflubenzuron, hexaflumuron); piperonyl butoxide; flonicamid; indoxacarb; and sulfafluoride.

[0317] Suitably, such additional pesticides or pesticide compounds may be included in the compositions of the present invention.

[0318] The methods of the invention may further comprise contacting the insect population or plant or part thereof with an additional insecticide or insecticidal compound (such as those described herein). Suitably, the additional insecticide or insecticidal compound is a kinin.

[0319] Suitably, any reference herein to a compound of the invention or a composition thereof may also refer to a compound of the invention in combination with one or more pesticides or pesticidal compounds, or a composition containing such a combination.

[0320] Suitably, there is provided a combination comprising a compound of the invention or a salt or solvate thereof and one or more peptides listed in the following table:

[0321]

[0322] In one embodiment, the compounds of the invention are used in combination with another pyrokinin, such as

[0323]

[0324]

[0325] In one embodiment, the compounds of the invention are used in combination with kinins, such as

[0326]

[0327] In one embodiment, the compounds of the invention are used in combination with a CAPA peptide (eg, a CAPA2 peptide).

[0328] In one embodiment, the compounds of the invention are used in combination with an AKH peptide, such as

[0329]

[0330] Suitably, combinations of any of the above compounds may be included in the compositions of the present invention.

[0331] The choice of adjunct or additional insecticide will generally depend on the particular target species.

[0332] Beneficial insect species

[0333] The compounds and compositions and combinations of the present invention are substantially non-toxic to beneficial insect species, including species that prey on pests and pollinator species. Important pollinator species, such as insects of the superfamily Apoidea, include honey bees, such as those of the genus Bombus, e.g., the European bumblebee. Important predatory species include Coccinellidae (ladybugs), such as Coccinella 2-spotted.

[0334] Substantially non-toxic means that the compounds and compositions and combinations of the present invention do not cause the death of beneficial insect species (e.g., pollinator species), and suitably means that they do not cause the premature death of beneficial insect species (e.g., pollinator species). This also means that the compounds and compositions and combinations of the present invention do not cause any harmful side effects to beneficial insect species (e.g., pollinator species), such as negatively affecting feeding behavior or locomotion.

[0335] Composition

[0336] The inventors provide compositions comprising at least one insecticidal compound of the present invention or a combination thereof, which can specifically bind to insects. Importantly, the compositions disclosed herein can inhibit, prevent or reduce one or more biological activities of insects by interacting with specific molecular structures (e.g., receptors, suitably neural receptors) of insects, thereby inhibiting, preventing or reducing the growth or fecundity of insects. In certain embodiments, the compositions disclosed herein can kill insects by specific interactions of at least one insecticidal compound contained in the composition, which can specifically bind to insect receptors.

[0337] The composition of the present invention or the composition used according to the present invention generally comprises the combination of the compound and one or more auxiliary components (e.g., solvent, carrier, diluent, adjuvant, preservative, dispersant, emulsifier or synergist). Suitably, the composition can be an agricultural composition, an insect control composition (e.g., an insecticide composition) or a plant protection composition.

[0338] In any of these embodiments, the compounds of the invention or the combination of compounds can be provided as part of a composition, such as an agricultural composition, an insect control composition (e.g., an insecticide composition) or a plant protection composition. Therefore, reference to the application or use of a compound or combination herein should be interpreted as covering the application or use of a suitable composition thereof, unless the context otherwise requires.

[0339] The compositions typically comprise a compound described herein in admixture with one or more auxiliary components such as solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifiers or synergists.

[0340] The composition may also comprise a combination with one or more additional active pesticides as described herein.

[0341] The present invention also provides a composition, such as an agricultural composition, an insect control composition or a plant protection composition, which comprises a compound of the present invention or a combination thereof mixed with one or more solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifiers or synergists. The composition can be an aqueous composition. Further details thereof will be explained below.

[0342] As used herein, "agriculture" refers to products suitable for use in agriculture or the agrochemical industry, including horticulture, floriculture, and home and garden uses, and also includes products for non-crop related uses, such as use by public health / pest control personnel to control unwanted insects and rodents, household uses, such as household fungicides and insecticides and agents, for protecting plants or plant parts, crops, bulbs, tubers, fruits (e.g. from harmful organisms, diseases or pests); for controlling, preferably promoting or increasing the growth of plants; and / or for promoting the yield of plants, crops or harvested plant parts (e.g., fruits, flowers, seeds, etc. thereof). Examples of such substances are clear to those skilled in the art, and preferably in the context of the present invention, include compounds with insecticide activity (e.g., contact insecticides or systemic insecticides, including household insecticides). Other such agrochemicals may be pesticides, growth regulators, nutrients / fertilizers, insect repellents, defoliants, etc.

[0343] As used herein, "agricultural use" includes not only the use of the pesticidal compounds of the present invention, their combinations or compositions, and optional agricultural chemicals as defined above (e.g., pesticides, growth regulators, nutrients / fertilizers, insect repellents, defoliants, etc.) suitable for and / or intended for use in field-grown crops (e.g., agriculture), but also includes the use of the compounds of the present invention, their combinations or compositions, and the agricultural chemicals as defined above intended for use in greenhouse-grown crops (e.g., horticulture / flower cultivation) or hydroponic cultivation systems, and even includes the use of the compounds of the present invention, their combinations or compositions, and agricultural chemicals as defined above suitable for and / or intended for non-crop uses, such as use in private gardens, household use (e.g., household herbicides or insecticides), or use by pest control personnel (e.g., weed control, etc.).

[0344] Suitably, the insect control composition according to the present invention is used to control insect colonies. The formulations of such compositions for controlling insect colonies are known to those skilled in the art, and include, but are not limited to, liquid emulsifiable concentrates, wettable powders, solutions, suspension concentrates, emulsions, suspoemulsions, granules and water dispersible granules (Mulqueen, 2003). Preferably, the insect control composition according to the present invention comprises the insecticidal compound of the present invention, and optionally a combination of other insecticidal compounds. Suitably, the insecticidal compound is contained in a carrier as described below.

[0345] The composition of the present invention may comprise a pesticidal formulation or an agrochemical formulation. "Pesticide formulation" as used herein refers to any composition comprising a compound or combination of compounds intended to prevent, eliminate, repel, attract or mitigate any harmful organism. "Agrochemical formulation" as used herein refers to a composition for agricultural use, comprising a bioactive agent, optionally further comprising one or more additives that are conducive to optimal dispersion, atomization, distribution, retention and / or activity of the agrochemical. As non-limiting examples, such additives are diluents, solvents, adjuvants, surfactants, wetting agents, spreading agents, oils, adhesives, penetrants, buffers, acidulants, defoamers or drift control agents.

[0346] Composition used herein refers to a composition comprising at least one active substance (suitably the insecticidal compound of the present invention), optionally further comprising one or more additives that are conducive to the optimal dispersion, atomization, deposition, leaf wetting, distribution, retention and / or absorption of the active substance. It can be clearly seen from the further description herein that the composition used herein includes biological insect control agents or biological insecticides, and these terms can be used interchangeably in this application. Therefore, the composition used herein includes a composition containing at least one biomolecule as an active ingredient, substance or element, for controlling harmful organisms in plants or other agricultural related environments (such as soil). Suitably, at least one of the biomolecules comprises the insecticidal compound of the present invention or a combination thereof. Suitably, wherein the harmful organism is an insect. As a non-limiting example, the additives in the composition disclosed herein may include but are not limited to diluents, solvents, adjuvants, surfactants, wetting agents, dispersants, oils, adhesives, thickeners, penetrants, buffers, acidulants, anti-settling agents, antifreeze agents, light protectants, defoamers, biocides and / or drift control agents.

[0347] Suitably, the composition of the invention is an aqueous composition.

[0348] The compound content of the composition can vary within a wide range. The compound concentration of the composition is suitably an effective amount and can be 0.0000001% to 95% by weight of the compound, preferably 0.0001% to 1% by weight. The terms "effective amount" and "effective dose" used herein refer to the amount required to achieve the desired result.

[0349] In a specific embodiment, the concentration of the compounds of the present invention included in the composition can be at least 0.0001% by weight. In a specific embodiment, the concentration of the compounds of the present invention included in the composition can be up to 50% by weight. In a specific embodiment, the concentration of the compounds of the present invention included in the composition can be 0.0001% to 50% by weight. In a specific embodiment, the present invention provides a composition comprising at least one insecticidal compound of the present invention, wherein the concentration range of at least one compound of the present invention in the composition is 0.001% to 50% by weight. In another specific embodiment, the concentration of at least one compound of the present invention included in the composition can be 0.001% to 50% by weight. In another specific embodiment, the concentration of at least one compound of the present invention included in the composition can be 0.01% to 50% by weight. In another specific embodiment, the concentration of at least one compound of the present invention included in the composition can be 0.1% to 50% by weight.

[0350] The composition of the present invention or the composition used according to the present invention may comprise a combination of more than one compound of the present invention, and / or a combination with other pesticidal compounds described herein. Thus, the composition of the present invention may, for example, comprise a first compound of the present invention and a second compound of the present invention, or a first compound of the present invention and a second pesticidal compound. Suitably, the first and second compounds may be any of those described herein, and may be present in the composition in any relative proportion.

[0351] The composition can be an aqueous composition, such as a saline composition. The aqueous composition can contain one or more buffers, such as a phosphate buffer (e.g., phosphate buffered saline) or a Tris buffer. Alternatively, the composition can be an oil dispersion or emulsion, such as an oil and water emulsion. Alternatively, the composition can be a natural and synthetic substance such as a suspension, powder, foam, paste, granule, aerosol, impregnated, or encapsulated in, for example, a polymeric substance. The appropriate form of the composition can be selected for the intended use according to the target insect and its habitat.

[0352] Adjuvants can enhance product performance, for example, by increasing the efficiency of delivery of the active ingredient, reducing the level of active ingredient required, or extending the spectrum of efficacy.

[0353] Different types of additives offer different benefits and advantages, which are achieved by adjusting properties such as spray formation, spray retention, wetting, deposit formation or absorption.

[0354] Adjuvants that modulate spray formation can influence spray quality by reducing spray drift and waste, allowing more product to reach the target. This can reduce usage rates, thereby improving environmental performance and providing a potentially more cost-effective solution. Such adjuvants include nonionic surfactants and emulsifier blends.

[0355] Adjuvants that regulate spray retention may dissipate the kinetic energy of the droplets during impact, meaning that the likelihood of bouncing or running off is reduced. Such adjuvants include alkyl polyglucosides, alkoxylated alcohols, and polyoxyethylene mono-branched alcohols (e.g., polyoxyethylene (8) mono-branched alcohol).

[0356] Adjuvants that modulate wetting properties (i.e., wetting agents) can reduce surface tension and contact angle, thereby improving coverage. Such adjuvants include polyoxyethylene sorbitan monolaurate (e.g., polyoxyethylene (8) sorbitan monolaurate), surfactant blends, and alkyl polyglucosides.

[0357] Auxiliary agents that regulate the formation of deposits can affect the evaporation of water from the droplets, thereby providing a more uniform distribution. Such adjuvants include alkoxylated polyol esters, polyoxyethylene sorbitan monolaurate (e.g., polyoxyethylene (12) sorbitan monolaurate), and alkyl polyglucosides.

[0358] Absorption-modulating adjuvants can enhance the penetration and absorption of active ingredients, for example through the insect cuticle, thereby increasing bioavailability. Such adjuvants include alkoxylated polyol esters and polyoxyethylene sorbitan monolaurates (e.g., polyoxyethylene (12) sorbitan monolaurate and polyoxyethylene (16) sorbitan monolaurate).

[0359] Dispersants can be aqueous or non-aqueous. Oil dispersion (OD) formulations usually include solid active ingredients dispersed in oil. The oil can be from paraffin solvent type to aromatic solvent type and vegetable oil or methylated seed oil. Usually, the active ingredient is uniformly suspended in the oil phase. Although mainly used for water-sensitive active ingredients, OD formulations extend to other active ingredients due to its better spray retention, diffusion, leaf absorption and penetration enhancement (such as passing through insect cuticle) because the carrier oil usually serves as an adjuvant.

[0360] Suitable oils for OD dispersions include linseed oil, rapeseed oil, and soybean oil.

[0361] Aqueous dispersants may be used, for example, to improve stability in a spray tank after dilution in water, and may include modified styrene acrylic polymers as well as polymeric amphoteric dispersants and adjuvants.

[0362] When the OD formulation is diluted before spraying, an emulsifier can be used to emulsify the continuous oil phase into water. Emulsifiers can be selected based on their ability to spontaneously form emulsions. Their performance depends primarily on the collective effect of the nature of the surfactant and their arrangement at the oil / water interface. Examples include polyoxyethylene sorbitol hexaoleate (e.g., polyoxyethylene (40) sorbitol hexaoleate), emulsifier blends, and calcium alkyl aryl sulfonates.

[0363] The composition may also contain a binder or a dye.

[0364] The compound may be provided in the form of a concentrate for dilution prior to administration. Alternatively, the compound may be provided in solid form for suspension or dissolution prior to formulation.

[0365] The compositions disclosed herein are themselves in quite different solid or liquid forms. As forms of solid compositions, mention may be made of dustable powders (the content of active substance may be up to 100%) and granules, in particular granules obtained by extrusion, by pressing, by impregnation of granular carriers, by granulation using powders as starting materials (in the latter case, the content of active substance in these granules is between 0.5% and 80%). Such solid compositions may optionally be used in liquid form of greater or less viscosity, depending on the desired type of application, for example by dilution in water. As forms of liquid compositions or forms intended to constitute liquid compositions during application, mention may be made of solutions, in particular water-soluble concentrates, emulsions, suspension concentrates, wettable powders (or spray powders), oils and waxes. Suspension concentrates are useful for spray applications and are prepared so as to obtain a stable fluid product which does not form deposits and they usually contain from 10% to 75% of active substance, from 0.5% to 15% of surfactant, from 0.1% to 10% of thixotropic agent, from 0% to 10% of suitable additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and binders, and as a vehicle water or an organic liquid in which the active substance is insoluble or only poorly soluble: some organic solids or inorganic salts may be dissolved in the vehicle to help prevent precipitation or as an anti-gel in water.

[0366] As used herein, "carrier" refers to any solid, semisolid or liquid carrier into or on which an active substance (e.g., a pesticidal compound or combination of the present invention) can be suitably incorporated, included, immobilized, adsorbed, absorbed, bound, encapsulated, embedded, attached or contained. Non-limiting examples of such carriers include nanocapsules, microcapsules, nanospheres, microspheres, nanoparticles, microparticles, liposomes, vesicles, beads, gels, weak ionic resin particles, liposomes, cochlear delivery vehicles, small particles, particles, nanotubes, buckyballs, water droplets as part of a water-in-oil emulsion, oil droplets as part of an oil-in-water emulsion, organic materials such as cork, wood or other plant-derived materials (e.g., in the form of seed hulls, sawdust, pulp, spheres, beads, flakes or any other suitable form), paper or paperboard, inorganic materials such as talc, clay, microcrystalline cellulose, silica, alumina, silicates and zeolites, or even microbial cells (e.g., yeast cells) or suitable fractions or fragments thereof.

[0367] In one embodiment, the carrier is a liposome. In one embodiment, the composition of the present invention suitably comprises one or more liposomes, wherein each liposome comprises a compound of the present invention or a combination thereof. Therefore, the present invention suitably provides a composition or formulation comprising a plurality of liposomes, wherein the liposome comprises a compound of the present invention or a combination thereof. Suitably, the liposome comprises a lipid component, which suitably may be soy lecithin and glycerol. Suitably, the liposome is formed of soy lecithin and glycerol. Suitably, the liposome is formed of 25 mg / ml glycerol and 3% glycerol. Suitably, the liposome comprises an effective concentration of a compound of the present invention. Suitably, the liposome comprises about 10 -4 M of the compound of the invention or a combination thereof. Therefore, the present invention suitably provides a composition or formulation comprising a plurality of liposomes comprising a compound of the invention or a combination thereof, soy lecithin (preferably 25 mg / ml) and glycerol (preferably 3%).

[0368] Suitably, liposomes may be made by the Mozafari heating method (Mozafari, MR "Nanoliposomes: preparation and analysis." Liposomes: Methods and Protocols, Vol. 1: Pharmaceutical Nanocarriers (2010): 29-50. Suitably, such a method comprises: (a) mixing a compound of the invention with glycerol, suitably a 50% glycerol solution, (b) mixing the mixture of step (a) with soy lecithin, suitably 350 mg of soy lecithin in aqueous solution, (c) heating the mixture of step (b) while stirring to form liposomes, suitably at about 60°C and about 800 RPM for about 40 minutes, (d) annealing the liposomes, suitably by placing the liposomes in water at 40°C for about 1-2 hours, and (e) sonicating the liposomes, suitably in an ultrasonic bath for about 30 minutes.

[0369] Suitably, the liposomes have a mean diameter of about 150 to 250 nm, suitably about 175 nm to 225 nm, suitably about 190 nm to 210 nm, suitably about 200 nm. Suitably, the size of the liposomes is determined by using dynamic light scattering (DLS), for example using a Malvern Zetasizer Nano. Suitably, the polydispersity index of the liposomes is between 0.25 and 0.35, suitably 0.26 to 0.33, suitably 0.26 to 0.31, suitably 0.26 to 0.30, suitably 0.26 to 0.29, suitably 0.26 to 0.28, suitably about 0.26.

[0370] In the composition of the present invention, the carrier containing one or more insecticidal compounds can be stored, for example, in the form of a wettable powder, wettable granules, emulsifiable concentrate, suspension concentrate, microemulsion, capsule suspension, dry microcapsule, tablet or gel, or suspended, dispersed, emulsified or otherwise brought into a suitable liquid medium (e.g., water or other suitable aqueous, organic or oily medium) to provide a (concentrated) liquid composition of the present invention having a stability that allows the composition of the present invention to be appropriately stored or (if necessary, after further dilution) applied to the intended site of action. Suitably, the composition of the present invention can be transported and / or stored prior to final use, optionally (and usually preferably) as a suitable liquid concentrate, dry powder, tablet, capsule suspension, slurry or "wet cake", which can be appropriately diluted, dispersed, suspended, emulsified or reconstituted in other appropriate ways by the end user prior to final use. The composition of the present invention allows application to the intended site of action using any suitable or desired manual or mechanical technique, such as spraying, pouring, dripping, brushing, coating, dripping, applying in the form of small droplets, mist or aerosol, or any other suitable technique. In one embodiment, the intended site of action is a whole living insect, and even more preferably, the surface of an insect.

[0371] The composition may be a bait composition for ingestion by target insects. The bait composition may contain one or more attractants, i.e., substances that entice insects to ingest the compound. Attractants may include artificial sweeteners, amino acids, other peptides or proteins, and carbohydrates (e.g., glucose, fructose, sucrose, maltose), etc. Examples include honey, syrup, and aqueous sucrose solutions.

[0372] Commercially available base formulations may also be suitable for formulating the compounds described in this specification, for example FMPC (Akzo Nobel).

[0373] The composition may include one or more synergists, compounds that increase the efficacy of the insecticide against its target, typically by inhibiting the insect's ability to metabolize active agents. Common synergists include piperonyl butoxide and MGK-264 (n-octylbicycloheptanedicarboximide) or peptidase inhibitors.

[0374] The composition may include one or more agents that promote the stability of the pesticidal compound of the present invention. Suitably, one or more agents that promote stability can prevent the degradation of the pesticidal compound of the present invention. Suitable agents that prevent the degradation of the pesticidal compound of the present invention can inhibit or reduce the activity of enzymes (suitably enzymes that act to degrade proteins, suitably proteases, for example). Therefore, suitably, the composition may include one or more protease inhibitors, suitably, which may be selected from: Bowman-Birk inhibitors, Kunitz inhibitors, cysteine ​​protease inhibitors, trypsin inhibitors, serine protease inhibitors, tannins, protease inhibitor-II (PI-II) and α-AI1.

[0375] The composition may also contain one or more additional attractants, bactericides, miticides, nematicides, fungicides, growth regulators or herbicides.

[0376] In some embodiments, the composition may include one or more other agricultural chemicals or agrochemicals, such as herbicides (e.g., contact herbicides or systemic herbicides, including household herbicides), fungicides (e.g., contact fungicides or systemic fungicides, including household fungicides), nematicides (e.g., contact nematicides or systemic nematicides, including household nematicides) and other pesticides or biocides (e.g., agents that kill insects or snails); as well as fertilizers; growth regulators, such as plant hormones; micronutrients, safeners, pheromones; repellents; insect baits; and / or active ingredients for modulating (i.e., increasing, decreasing, inhibiting, enhancing and / or triggering) gene expression (and / or other biological or biochemical processes) in target plants (e.g., plants to be protected or plants to be controlled), such as nucleic acids (e.g., single-stranded or double-stranded RNA, such as used in the context of RNAi technology) and other factors, proteins, chemicals, etc. known for this purpose.

[0377] Examples of such agricultural chemicals are clear to those skilled in the art; for example, they include, but are not limited to, glyphosate, paraquat, isopropylamine, acetochlor, mesotrione, 2,4-D, atrazine, glufosinate, sulfamethoxam, oxadiazine, pendimethalin, picloram, trifluralin, bromoxynil, chlorpyrifos, fluroxypyr, nicosulfuron, benzylsulfuron, imidazole thiocarb, dicamba, imidacloprid, thiamethoxam, fipronil, chlorpyrifos, deltamethrin, cyhalothrin, endosulfan , methamidophos, carbofuran, clothianidin, cypermethrin, avermectin, fluazifop, spinosad, indoxacarb, bifenthrin, tefluthrin, myclobutanil, thiamethoxam, tebuconazole, mancozeb, cyazofamid, fluazinam, pyraclostrobin, epoxiconazole, thiophanate-methyl, copper fungicides, trifloxystrobin, prothioconazole, fenpropimorph, carbendazim, propiconazole, methyl thiophanate, sulfur, boscalid, chlorantraniliprole and other known agricultural chemicals or any suitable one or more combinations thereof.

[0378] Method for producing insecticidal compounds

[0379] The pesticidal compounds described herein can be produced by any method known in the art for producing peptides. In one embodiment, the pesticidal compounds can be produced by chemical methods, suitably chemical synthesis methods.

[0380] Any suitable chemical method may be used to synthesize the pesticidal compounds of the present invention.

[0381] Suitable insecticidal compounds are peptides. Therefore, they are suitably synthesized by solid state peptide synthesis. Suitably, this synthesis can be carried out by using commercially available machines, such as Biotage Initiator+Alstra microwave-assisted peptide synthesizer or CEM Liberty Prime microwave-assisted peptide synthesizer.

[0382] In one embodiment of the invention, the insecticidal compound is a peptide of the formula: [Hy]-NADEDQQQSVDFTPRL-[NH2] (SEQ ID NO: 2). Suitably, the peptide can be synthesized by the method defined in the examples. Suitably, by Figure 2 The method defined in .

[0383] In another aspect of the present invention, there is provided an isolated pesticidal compound produced by the method of the present invention. Suitably, an isolated pesticidal compound of formula (I) is produced by the method of the present invention.

[0384] In another aspect of the present invention, a method for producing the composition disclosed herein is provided, the method comprising at least the steps of: (a) obtaining at least one pesticidal compound of formula (I), and (b) formulating the pesticidal compound into a composition.

[0385] In another aspect of the invention, a method for producing and / or manufacturing a variant of an insecticidal compound of formula (I) is provided. This may comprise the following steps: (i) modifying peptide Z of formula (I) by adding, replacing or deleting at least one amino acid; (ii) evaluating the insecticidal activity of the variant thus produced, and - optionally - at least one property selected from the group consisting of biological stability, chemical stability, bioavailability, solubility (including the ability to form stable formulations), manufacturability and production costs. When the insecticidal activity is reduced compared to unmodified peptide Z, the process of steps (i) and (ii) is repeated until a variant with improved insecticidal activity is obtained. When the insecticidal activity is improved compared to unmodified peptide Z, the method may comprise the further steps of manufacturing, isolating and purifying the variant. Screening for insecticidal activity and other above-mentioned properties may be performed as described below or as generally known to those skilled in the art.

[0386] In one embodiment, there is provided a method for making a variant of the pesticidal compound of the present invention, the method comprising the steps of:

[0387] a) modifying peptide Z by adding, substituting or deleting at least one amino acid;

[0388] b) evaluating the pesticidal activity capacity of the variant, and - optionally - at least one property selected from the group consisting of: biological stability, chemical stability, bioavailability, solubility (including the ability to form stable formulations), manufacturability and production cost;

[0389] c) when the insecticidal activity is reduced compared to the insecticidal compound comprising unmodified peptide Z, repeating the process of steps (a) and (b) until a variant with improved insecticidal activity is obtained;

[0390] d) when the insecticidal activity is improved compared to the insecticidal compound comprising unmodified peptide Z, further producing, isolating and purifying the variant.

[0391] Suitably, the step of obtaining at least one pesticidal compound comprises (a) chemically synthesizing the pesticidal compound.

[0392] Suitable compositions are as described above. Suitable manufacturing methods for preparing the composition are known in the art and include, but are not limited to, high or low shear mixing, wet or dry grinding, drop casting, encapsulation, emulsification, coating, encapsulation, pelleting, extrusion granulation, fluidized bed granulation, coextrusion, spray drying, spray cooling, atomization, addition or condensation polymerization, interfacial polymerization, in-situ polymerization, coagulation, spray encapsulation, cooling melt dispersion, solvent evaporation, phase separation, solvent extraction, sol-gel polymerization, fluidized bed coating, pan coating, melting, passive or active absorption or adsorption.

[0393] The features disclosed in the preceding description, or in the following claims, or in the accompanying drawings, expressed in their specific form or in terms of means for performing the disclosed functions, or methods or processes for obtaining the disclosed results, as the case may be, may be used alone or in any combination of such features to implement various forms of the invention.

[0394] Although the present invention has been described in conjunction with the above exemplary embodiments, many equivalent modifications and variations will be apparent to those skilled in the art when this disclosure is given. Therefore, it is considered that the exemplary embodiments of the present invention set forth above are illustrative rather than restrictive. Various changes may be made to the embodiments without departing from the spirit and scope of the present invention.

[0395] To avoid any doubt, any theoretical explanations provided herein are given only for the purpose of enhancing the reader's understanding. The inventors do not wish to be bound by any of these theoretical explanations.

[0396] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. BRIEF DESCRIPTION OF THE DRAWINGS

[0397] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying drawings, in which:

[0398] Figure 1 The chemical structure of SB-P-80 is shown;

[0399] Figure 2 The chemical synthesis route for synthesizing SB-P-80 is shown;

[0400] Figure 3 The experimental setup for the artificial diet assay for Lepidoptera is shown;

[0401] Figure 4 Data are shown for the activity of unformulated SB-P-80 against Spodoptera frugiperda after 168 hours. One larva was assayed per cell. (n=10).

[0402] Figure 5 Data showing the activity of peptide SB-P-80 against Plutella xylostella after an in-laboratory spray assay conducted by FERA;

[0403] Figure 6 Activity data for the unformulated peptide SB-P-80 against Spodoptera frugiperda following leaf disc assay are shown;

[0404] Figure 7 Field trial data showing % control of peptide SB-P-80 against diamondback moth (Plutella xylostella) in Botrytis cinerea (cauliflower);

[0405] Figure 8Field trial data showing % control of peptide SB-P-80 against Trichoplusia ni (cabbage looper) in Botrytis cinerea (cauliflower).

[0406] Examples

[0407] The present invention will now be demonstrated and further described by the following non-limiting examples.

[0408] General Procedures

[0409] Unless otherwise indicated, all amino acids are in the l-configuration. Standard Fmoc-protected amino acids were purchased from CEM Corporation or Pepteuticals. Suppliers of specialty amino acids are noted where appropriate, as are suppliers of peptide synthesis resins. Peptide-grade DMF was purchased from Rathburn.

[0410] Peptides were synthesized on a Biotage Initiator+ Alstra microwave-assisted peptide synthesizer or a CEM Liberty Prime microwave-assisted peptide synthesizer, as designated.

[0411] High-resolution mass spectrometry (HRMS) was performed on a Bruker microTOF-Q II (ESI+).

[0412] The peptide was purified using a Phenomenex, Gemini, C18, 5 μm, 250 x 21.2 mm column on a reverse phase Dionex HPLC system equipped with a Dionex P680 pump and a Dionex UVD170U UV-vis detector (monitored at 214 nm and 280 nm). Gradient elution was performed using a solvent consisting of A (H2O + 0.1% TFA) and B (MeCN + 0.1% TFA), and the fractions were then lyophilized using a ChristAlpha 2-4LO plus lyophilizer.

[0413] Pure peptides were analyzed on a Shimadzu reverse phase HPLC (RP-HPLC) system equipped with a Shimadzu LC-20AT pump, a SIL-20A autosampler, and a SPD-20A UV-vis detector (monitored at 214 nm and 280 nm) using a Phenomenex (Aeris, 5 μm, Peptide XB-C18, 150 x 4.6 mm) column at a flow rate of 1 mL / min. The RP-HPLC gradient was run using a solvent system consisting of solution A (100% H2O + 0.1% TFA) and B (100% MeCN + 0.1% TFA). Typically, two gradients were used to characterize each peptide; a gradient from 5% to 95% Solution B over 20 minutes (with a 2-minute hold at 5% Solution B and a 5-minute wash at 95% Solution B at the beginning and end of the gradient, respectively) and a gradient from 5% to 95% Solution B over 50 minutes (with a 5-minute hold at 5% Solution B and a 5-minute wash at 95% Solution B at the beginning and end of the gradient, respectively). In some cases, specialized gradients were used and this is indicated where appropriate. Analytical RP-HPLC data are reported as column retention times (tR) in minutes (min). The analytical column was maintained at ambient temperature.

[0414] LC-MS analysis was performed on a Thermo Scientific LCQ Fleet quadrupole mass spectrometer with an m / z range of 50-2000Da, with an ESI source coupled to a Dionex Ultimate 3000LC. Analysis was performed on a ReprosilGold120C18, 3μm 150x 4mm column, using a linear gradient from buffer A (95 / 5H2O / MeCN, containing 0.1% v / v TFA) to buffer B (95 / 5MeCN / H2O, containing 0.1% v / v TFA) over 20 minutes (at the beginning and end of the gradient, 2 minutes at 0% solution B and 5 minutes at 100% solution B, respectively). If a dedicated analytical RP-HPLC gradient was used to characterize the compound, a similar LC-MS gradient was used. Analytical RP-HPLC and LC-MS samples were injected as 25 μL of a stock solution at a concentration of 1 mg / mL in H2O / MeCN containing 0.1% v / v TFA. The LC-MS column oven temperature was maintained at 30°C.

[0415] Pure peptides were subjected to high-resolution mass spectrometry (HRMS) analysis on a Bruker microTOF-Q II (ESI+).

[0416] Proton NMR spectra for calculating peptide content ( 1H NMR) was recorded on an AVANCE III 400 Bruker (400 MHz). Proton chemical shifts are expressed in parts per million (ppm, δ scale) and are referenced to residual protium in the NMR solvent (CDCl3, δ 7.26; CD3OD, δ 3.31 and D2O, δ 4.79). Where appropriate, the following abbreviations are used to describe peak patterns: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. Coupling constants J are reported in Hertz units (Hz).

[0417] General procedure for automated peptide synthesis

[0418] Biotage initiator + Alstra synthesizer:

[0419] Fmoc protected amino acids were prepared as 0.2M (0.1mmol synthesis), 0.5M (0.2mmol synthesis) or 0.7M (0.5mmol synthesis) solutions in DMF. 5 equivalents of amino acids (relative to resin loading) were used during the coupling cycle. Oxyma and diisopropylcarbodiimide (DIC) were prepared as 0.2M (0.1mmol synthesis), 0.5M (0.2mmol synthesis) or 0.7M (0.5mmol synthesis) solutions in DMF. 5 equivalents of Oxyma and 5 equivalents of DIC (relative to resin loading) were used during the coupling cycle. For Fmoc deprotection, a solution of 20% morpholine (containing 5% formic acid) in DMF was used. Except for Fmoc-Cys(Trt)-OH, Fmoc-His(Trt)-OH and Fmoc-Arg(PBf)-OH, the coupling reactions were carried out at 90°C for 2 minutes under microwave heating. The coupling of Fmoc-Cys(Trt) and Fmoc-His(Trt)-OH was performed at 50°C for 10 minutes. The coupling of Fmoc-Arg(Pbf)-OH was performed at 90°C for 2 minutes in 2 consecutive cycles (double coupling). Microwave-assisted Fmoc deprotection was performed at 90°C for 1 minute.

[0420] CEM Liberty Blue Synthesizer

[0421] The Fmoc protected amino acid was prepared as a 0.2M solution in NBP (Tamisolve). 5 equivalents of amino acid (relative to the resin load) were used during the coupling cycle. Oxyma was prepared as a 0.5M solution in NBP. DIC was prepared as a 5M solution in NBP. 5 equivalents of Oxyma and 5 equivalents of DIC (relative to the resin load) were used during the coupling cycle. For Fmoc deprotection, a 20% pyrrolidine solution was used. Except for Fmoc-Cys(Trt)-OH, Fmoc-His(Trt)-OH and Fmoc-Arg(Pbf)-OH, the coupling reaction and Fmoc deprotection were carried out at 90°C microwave heating for 2min and 1min, respectively. The coupling of Fmoc-Cys(Trt) and Fmoc-His(Trt)-OH was carried out at 50°C for 5min. The coupling of Fmoc-Arg(Pbf)-OH was carried out at 75°C for 2 consecutive cycles of 5 minutes.

[0422] General procedure for TFA cleavage of peptides

[0423] Typically, the cleavage test of the peptide was performed by taking about 3 mg of the dried resin beads and treating them with TFA / TIS / water (95:2.5:2.5) for 3 hours. The filtrate was drained, concentrated, and then triturated in cold ether (Et2O). The triturate was dissolved in acetonitrile / water and analyzed by RP-HPLC / LC-MS.

[0424] Peptides were generally cleaved from the resin in bulk by gently shaking the resin in a cleavage mixture of TFA / TIS / H2O (95:2.5:2.5) for 3 h at room temperature, then draining it and blowing off the TFA with a steady stream of N2. Peptides containing cysteine ​​or tryptophan residues were cleaved from the resin using a cleavage mixture of TFA / TIS / H2O / DODT (94:2.5:1:2.5) for 3 h. In all cases, the crude peptide was triturated with cold Et2O. Et2O was removed from the resulting crude peptide precipitate under a steady stream of nitrogen. The crude peptide was then redissolved in H2O / MeCN and purified by RP-HPLC.

[0425] The specific synthetic route of SB-P-80 is as follows Figure 2 For the synthesis of SB-P-80, the double coupling method was used for 9Ser, 11Asp, and 13Thr. Extended 6-min coupling was used for 3Asp, 4Glu, 5Asp, 6Gln, and 7Gln, and 7-min arginine coupling was used for 15Arg.

[0426] Unless otherwise indicated herein, peptides were either synthesized according to the general procedures described above, according to the exemplary procedures below, or ordered directly.

[0427] Mortality Assessment Methods

[0428] Lepidoptera artificial diet assay

[0429] Frontier Lepidoptera Artificial Diet is prepared as 1% agar and then mixed with artificial diet powder. The peptide solution is divided equally into 10 wells and the diet is poured directly onto them. The final concentration of the peptide is 1x 10 -4 M, each peptide was aliquoted into 10 pools. Once the diet solidified and cooled, each pool was infested with one L1 larva. The trays were heat sealed and the larvae were allowed to develop for 168 h. Finally, pupation and mortality were scored. The Lepidoptera artificial diet assay was set up as shown in Figure 3 SB-P-80 was used in the artificial diet assay for Lepidoptera and compared with the negative control vehicle and the insecticide dichlorodiphenyltrichloroethane (DDT). The activity of SB-P-80 was shown in Figure 4 As shown; Unlike broad-spectrum chemical insecticides such as DDT, SB-P-80 has higher activity, is environmentally friendly and targets specific pests.

[0430] Lepidoptera spray assay

[0431] FERA conducted a laboratory spray trial in which four cabbage plants were sprayed with 2X 10 - 4 The peptide SB-P-80 at M (with and without Silwet-408) was sprayed from above at a rate of 200 L / Ha using a laboratory spray chamber. The plants were allowed to air dry and then twenty larvae of the diamondback moth (2nd / 3rd instar) were added to each plant, which were then covered with ventilated bags and secured with elastic bands. The plants were placed in plastic containers and watered from below. The plants were then placed under experimental conditions: the CE chamber was set to 20°C and 65% rh with a 16 h light: 8 h dark lighting scheme. The mortality of the insects was evaluated 7 days after spraying the peptide and compared with the chemical insecticide "Gazelle". SB-P-80 proved to be very effective in killing insects, with an effect comparable to that of chemical products. The results are shown in Figure 5 shown.

[0432] Lepidoptera leaf disc assay

[0433] The leaf disc assay was adapted from IRAC Susceptibility Testing Method 018 (https: / / irac-online.org / methods / plutella-xylostella-larvae / ?ext=pdf).

[0434] Place a 9 cm diameter filter paper in a petri dish and wet it, ensuring that no water reservoir exists to prevent potential larval damage. Select a brassica leaf that fits the petri dish and soak it in 2 x 10-4 The leaves were gently shaken to remove excess liquid and this process was repeated ten times per treatment. Each leaf of each replicate was then infested with one L1 larva, as larvae are highly aggressive and exhibit cannibalistic tendencies. Petri dishes were sealed with folded tissue and rubber bands were used to stack the dishes, minimizing the risk of larval escape. The dishes were placed in a humidity chamber at 25 °C, with approximately 60% relative humidity and a 16:8 light-dark cycle. Observations were performed daily for up to 6 to 10 days, depending on the extent of leaf consumption. Leaf dip assays were performed using SB-P-80 and compared to a negative control vehicle and a current commercial insecticide, chlorantraniliprole. The activity of SB-P-80 against the fall armyworm is shown in Figure 6 As shown; unlike broad-spectrum chemical insecticides, SB-P-80 has good activity while being environmentally friendly and targeting specific pests.

[0435] Field trials

[0436] Collins Agricultural Consultants, Inc. conducted a field trial in the United States and studied the effect of 1X10 -4 The efficacy of insecticidal peptide SB-P-80 of M against Plutella xylostella (Spodoptera exigua) on cabbage (cauliflower) crops. The two applications were separated by 7 days, where DAA represents the number of days after the first application of A, and DAB represents the number of days after the second application of B. The experiment observed that SB-P-80 had excellent insecticidal activity in this case, such as Figure 7 shown.

[0437] Collins Agricultural Consultants, USA, conducted further field trials in a similar manner to the above, studying the concentration of 1X 10 -4 The efficacy of insecticidal peptide SB-P-80 from M against Trichoplusia ni (cabbage looper) on cabbage (cauliflower) crops. The test observed that the insecticidal activity of SB-P-80 in this case achieved excellent results, such as Figure 8 shown.

[0438] References

[0439] In order to more fully describe and disclose the present invention and the prior art in the field to which the present invention belongs, a number of publications are cited. The complete citations of these references are provided below. The entire contents of each of these references are incorporated herein by reference.

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[0450] ○Terhzaz S,Alford L,Yeoh JGC,Marley R,Dornan AT,Dow JAT and DaviesSA,Renal neuroendocrine control of desiccation and cold tolerance byDrosophila suzukii.Pest Manag Sci 74:800-810(2017).

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[0452] ○Lamango NS,Nachman RJ,Hayes TK,Strey Aand Isaac RE,Hydrolysis ofinsect neuropeptides by an angiotensin converting enzyme from the housefly,M.domestica.Peptides 18:47-52(1997).

[0453] ○Terhzaz S,Cabrero P,Robben JH,Radford JC,Hudson BD,Milligan G,DowJAand Davies SA,Mechanism and function of Drosophila capa GPCR:a desiccationstress-responsive receptor with functional homology to human neuromedinUreceptor.PLoS One 7(1):e29897(2012).

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[0455] ○Dow JAT,Maddrell SHP,Gortz A,Skaer NJV,Brogan S and Kaiser K,TheMalpighian tubules of Drosophila melanogaster–a novel phenotype for studiesof fluid secretion and its control.J Exp Biol 197:421-428(1994).

[0456] ○Davies SA,Huesmann GR,Maddrell SH,O’Donnell MJ,Skaer NJ,Dow JAT andTublitz NJ,CAP2b,a cardioacceleratory peptide,is present in Drosophila andstimulates tubule fluid secretion via cGMP.Am J Physiol 269:R1321–R1326(1995).

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[0458] ○Sadeghi A.,Van Damme,EJMand Smagghe G.(2009)Evaluation of thesusceptibility of the pea aphid,Acyrthosiphon pisum,to a selection of novel biorational insecticides using an artificial diet.Journal ofInsect Science 9:65.

[0459] ○Van Emden F(2009).Artificial diet for aphids–thirty years'experience.REDIA,XCII:163-167。

Claims

1. An insecticidal compound having the following formula (I), or a salt or solvate thereof: R 1 -Y 1 -Z-Y 2 -R 2 (I) in: R 1 is hydrogen (which may be designated as "H-" or "Hy-"), C 1-4 Alkyl (e.g., methyl, ethyl, propyl, butyl), formyl, acyl, fatty acyl, sugar moiety, phosphate or sulfate, or R 1 is the pyroglutamic acid group of the formula: Any alkyl, formyl, acyl or fatty acyl group may be optionally substituted with one or more oxo or C 1-6 Alkyl or sugar moieties, phosphate or sulfate group substitution; Y 1 Absent or a peptide consisting of 1 to 2 amino acids; Z is a peptide according to the formula: NADEDQQQSVDFTPRL(SEQ ID NO:1); Y 2 Absent or a peptide consisting of 1 to 2 amino acids; R 2 NH2、NR 2a H, NR 2a R 2b , OH or OR 2a ; where R 2a and R 2b If present, each is independently C 1-6 - alkyl (eg methyl, ethyl, propyl, butyl, pentyl or hexyl).

2. The insecticidal compound as claimed in claim 1, wherein R 1 is selected from hydrogen, acyl or fatty acyl, or phosphate or sulfate, or R 1 is the pyroglutamic acid group of the formula: wherein the acyl or fatty acyl group is optionally substituted with a sugar moiety, phosphate or sulfate.

3. The insecticidal compound according to claim 1 or 2, wherein R 1 Selected from hydrogen, formyl, acetyl (Ac), propionyl, butyryl, palmitoyl, butyryl, cerroyl, decanoyl, docosenoyl, dodecanoyl, tauroyl, heptanoyl, hexanoyl, eicosanoyl, eicosenoyl, tetracosanoyl, linoleoyl, lipoyl, myristoyl, nonanoyl, octadecanoyl, octanoyl, palmitoyl, stearoyl, undecanoyl, valeryl and a pyroglutamic acid radical of the formula: Preferably, wherein R 1 is selected from hydrogen or palmitoyl, more preferably, wherein R 1 It's hydrogen.

4. A pesticidal compound as claimed in any one of the preceding claims, wherein: Y 1 does not exist; and / or where Y 2 is present and is selected from: GR, RG, KR, RK, K, R and G; and / or Where R 2 It's NH2.

5. The insecticidal compound of claim 1 having the formula: [Hy]-NADEDQQQSVDFTPRL-[NH2] (SEQ ID NO: 2).

6. A composition comprising a compound as described in any one of claims 1 to 5 mixed with one or more solvents, carriers, diluents, adjuvants, preservatives, dispersants, emulsifiers or synergists; optionally, wherein the composition is an aqueous composition, preferably wherein the composition comprises an effective amount of the compound.

7. The composition of claim 6, wherein the composition is an agricultural composition, preferably wherein the composition is an insect control composition or a plant protection composition.

8. Use of a compound as claimed in any one of claims 1 to 5 or a composition as claimed in claim 6 or 7 as an insect control agent or as a plant protection agent for protecting plants or parts thereof from insects.

9. The use of the compound or composition as claimed in claim 8 for: a) Diptera, preferably wherein the Diptera are selected from Drosophila melanogaster or Drosophila suzukii; b) insects of the order Hemiptera, such as aphids, preferably wherein the insects of the order Hemiptera are selected from the group consisting of: beet aphid, cotton aphid, pea aphid, peach aphid or cereal aphid; and / or c) Lepidoptera, preferably wherein the Lepidoptera are selected from the group consisting of Plutella xylostella, Spodoptera frugiperda or Trichoplusia ni; d) Insects of the order Blattodea; and / or e) Coleoptera, Preferably, the use of the compound as claimed in claim 8 is against the fall armyworm insect.

10. A method of increasing insect mortality, the method comprising contacting an insect or insect population with a compound as claimed in any one of claims 1 to 5 or a composition as claimed in claim 6 or 7.

11. A method of inhibiting or preventing insect infestation of plants, the method comprising contacting the plant or part thereof, or the locus where the plant is growing or is expected to grow, with a compound as claimed in any one of claims 1 to 5 or a composition as claimed in claim 6 or 7.

12. The method of claim 11, wherein the compound or composition is contacted with the plant or part thereof, or the locus where the plant is growing or is expected to grow, when the plant or part thereof is free or substantially free of insects.

13. A method of reducing or treating insect infestation of a plant or reducing the insect load on a plant, the method comprising contacting the plant or part thereof, or the locus where the plant is growing, with a compound as claimed in any one of claims 1 to 5 or a composition as claimed in claim 6 or 7.

14. The method of claim 11 or 12, wherein the location at which the plant is growing or is expected to grow comprises an agricultural location suitable for growing plants, preferably the location comprises a field.

15. The method of any one of claims 10 to 14, wherein the insects are: a) Diptera, preferably wherein the Diptera are selected from Drosophila melanogaster or Drosophila suzukii; b) insects of the order Hemiptera, such as aphids, preferably wherein the insects of the order Hemiptera are selected from the group consisting of beet aphid, cotton aphid, pea aphid, peach aphid or cereal aphid; c) Lepidoptera, preferably wherein the Lepidoptera are selected from the group consisting of Plutella xylostella, Spodoptera frugiperda or Trichoplusia ni; d) Insects of the order Blattodea; and / or e) Coleoptera, Preferably, wherein the insects are fall armyworm insects.

16. The method of any one of claims 10 to 15, wherein contacting the insect or insect population, plant or part thereof, or locus comprises treating the insect or insect population, plant or part thereof, or locus with the compound or composition by irrigating, feeding, spraying, misting, foaming, fogging, hydroponically, hydroponically, coating, immersing, injecting, and / or encrusting.

17. The method of any one of claims 10 to 16, wherein the insect or insect population, plant or part thereof, or locus is contacted with an effective concentration of the compound, preferably within 10 -3 M to 10 -9 The concentration between M.

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