NZ760403B2 - Control of resistant pests - Google Patents

Control of resistant pests Download PDF

Info

Publication number
NZ760403B2
NZ760403B2 NZ760403A NZ76040318A NZ760403B2 NZ 760403 B2 NZ760403 B2 NZ 760403B2 NZ 760403 A NZ760403 A NZ 760403A NZ 76040318 A NZ76040318 A NZ 76040318A NZ 760403 B2 NZ760403 B2 NZ 760403B2
Authority
NZ
New Zealand
Prior art keywords
ppm
hydrogen
resistant
formula
compound
Prior art date
Application number
NZ760403A
Other versions
NZ760403A (en
Inventor
Robert Klupacs
Peter May
Original Assignee
Bio Gene Technology Limited
Filing date
Publication date
Application filed by Bio Gene Technology Limited filed Critical Bio Gene Technology Limited
Priority claimed from PCT/AU2018/050704 external-priority patent/WO2019006516A1/en
Publication of NZ760403A publication Critical patent/NZ760403A/en
Publication of NZ760403B2 publication Critical patent/NZ760403B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/06—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing keto or thioketo groups as part of a ring, e.g. cyclohexanone, quinone; Derivatives thereof, e.g. ketals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/34—Nitriles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds
    • A01N57/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds containing heterocyclic radicals

Abstract

The present invention relates to methods of controlling pesticide resistant pests comprising exposing the pesticide resistant pests to a pest controlling amount of a triketone compound.

Description

Control of Resistant Pests Field of the Invention The present invention relates to methods of controlling pesticide resistant pests comprising exposing the pesticide resistant pests to a pest controlling amount of a triketone compound of formula (I).
Background of the Invention Pesticide resistance is a signi?cant agricultural problem and the incidence of pesticide resistance is increasing. In the 1940s, farmers in the USA lost about 7% of crops to pests and this increased to 13% in the 19805 and 1990s even though more pesticides were available. It has been estimated that up to 1000 pest species have developed resistance to one or more pesticides since 1945.
An e is grain protectants. Grain protectants are pesticides applied to grains that are to be stored to prevent damage from pest species such as the lesser grain borer (Rhyzopertha ca (F.)), the rice weevil (Sitophilus oryzae (L.)), the rust red ?our beetle (Tribolz'um castaneum t)), the saw toothed grain beetle (Oryzaephilus suranamensis (L.)) and the ?at grain beetle (prtolestesfermgineus (Stephens)).
Grain protectants have been used for several decades and resistance is now a problem.
(Daglish, 2008, J Stored Products Research, 44:71-76). For e, in many States of Australia, the lesser grain borer cannot be controlled with any organophosphate or synthetic pyrethroid and ance to the insect growth regulator methoprene is becoming common (Daglish, er al. 2013, J Stored Products Research, 54:71-76).
Organophosphate resistance is also common in the saw toothed beetle. id="p-4" id="p-4" id="p-4" id="p-4"
[0004] Pesticide resistance may also occur in pests that infest agriculturally useful animals such as cattle. For example, cattle ticks are serious pests in cattle hout tropical and sub-tropical areas of the world. Infestations cause high tion losses through weight loss, reduced milk yields and hide damage. The cattle tick may also transmit tick fever organisms such as Babesia and Anaplasma, which can cause high morbidity amongst susceptible s.
Control of ticks is usually done using an integrated pest management , where treatment using more than one ide occurs. However, to reduce development of resistance, more s for pesticides, particularly those with varying mechanisms of action, are required.
The present invention is predicated, at least in part, by the discovery that ?avesone, a potassium channel tor, is effective in controlling pesticide resistant pests, particularly agriculturally important pests that have developed ance to commonly used pesticides, such as stored grain pests and cattle ticks and ?ies.
Summary of the invention In one aspect of the invention, there is provided a method of controlling ide resistant pests comprising exposing the pesticide resistant pests to a compound of formula (1) R1 R2 0 0 R3 R6 R4 R5 0 (I) wherein R1 is selected from —C(=O)R7, -OR8, -SR8, -C1-1ohydroxyalkyl, - NR9R10, -C(=N-R9)R7, -C(=N—OH)R7, -NO, -N02, -N(OR8)R’7 and —OSO3R8; R2 is selected from hydrogen, -C1-1oalkyl, alkenyl, aryl and heteroaryl; R3, R4, R5 and R6 are each independently ed from hydrogen, -C1-1oalkyl, -C3_ alkyl, -C2_10alkenyl, -C1_10haloalkyl, -C1_10dihaloall lotrihaloalkyl, -OR8, -SR8, -NR9R10, -C(=N—R9)R7, —NO, -N02, -NR9OR8, -OSO3R8, -C1— malkylaryl and —C(=O)R7; R7 is selected from hydrogen, -C1-10alkyl, -C2-1oalkylaryl, Cmcycloalkyl, -C2- loalkenyl, -C1-1oalkylheteroaryl, -C1-1ohaloalkyl, -C1-1odihaloalkyl, -C1_ 10trihaloalkyl, -C1-1ohaloalkoxy, hydroxyalkyl, -C1-1othioalkyl, —C1_ lonitroalkyl, -C1-3alkleC1.3alkyl, -C1-3alkleC1-3haloalkyl, -C1.3alkleC1- 3dihaloalkyl, -C1.3alkleC1-3trihaloalkyl, -OR8, -SR8 and —NR9R10; R8 is selected from hydrogen, -C1-ioalkyl, -C2-1oalkylaryl, -C3-6cycloalkyl, -C2- nyl, -C1-10alkylheteroaryl, -C1-1ohaloalkyl, -C1-1odihaloalkyl, -C1_ lotrihaloalkyl, -C1-1ohaloalkoxy, -C1-1ohydroxyalkyl, -C1_1othioalkyl and -C1_10nitroalkyl; R9 and R10 are independently selected from hydrogen, -C1-1oalkyl, -C2-1oalkylaryl, -C3— scycloalkyl, -C2_10alkenyl, -C1-1oalkylheteroaryl, -C1_10haloalkyl, -C1-10dihaloalkyl, -C1- lotrihaloalkyl, or a tautomer thereof.
In another aspect of the present invention, there is provided a method of treating or preventing a pest infestation or infection in a livestock animal or a companion animal comprising applying to the animal an effective amount of a compound of a (I) R1 R2 0 0 R3 R6 R4 R5 0 (I) wherein R1 is selected from —C(=O)R7, -OR8, -SR8, -C1-1ohydroxyall NR9R10, R9)R7, OH)R7, -NO, -N02, -N(OR8)R7 and —OSO3R3; R2 is ed from hydrogen, -C1—1oalkyl, -C2-1oalkenyl, aryl and heteroaryl; R3, R4, R5 and R6 are each independently selected from hydrogen, -C1-1oalkyl, -C3_ scycloalkyl, -C2-10alkenyl, -C1-1ohaloalkyl, -C1-1odihaloall iotrihaloalkyl, -OR3, 'SR8, -NR9R10, -(C=N—R9)R7, -NO, -N02, -NR9OR8, 'OSO3R8, -C1- malkylaryl and —C(=O)R7; R7 is selected from hydrogen, -C1-10alkyl, -C2-1oalkylaryl, Cmcycloalkyl, -C2- ioalkenyl, -C1-1oalkylheteroaryl, -C1_1ohaloalkyl, -C1_10dihaloalkyl, -C1- aloalkyl, haloalkoxy, -C1-1ohydroxyalkyl, -C1-1othioalkyl, —C1_ oalkyl, -C1-3alkleC1.3alkyl, -C1-3alkleC1-3haloalkyl, -C1.3alkleC1- oalkyl, -C1.3alkleC1-3trihaloalkyl, -OR8, -SR8 and —NR9R10; R8 is selected from hydrogen, -C1-1oalkyl, -C2-1oalkylaryl, -C3-6cycloalkyl, -C2- 10alkenyl, -C1-1oalkylheteroaryl, -C1-1ohaloalkyl, dihaloalkyl, -C1_ lotrihaloalkyl, -C1-1ohaloalkoxy, -C1-1ohydroxyalkyl, -C1_10thioalkyl and -C1_10nitroalkyl; R9 and R10 are independently selected from hydrogen, -C1-10alkyl, -C2-1oalkylaryl, -C3_ scycloalkyl, -C2-10alkenyl, -C1-1oalkylheteroaryl, -C1-1ohaloalkyl, -C1-1odihaloalkyl, -C1_ lotrihaloalkyl, or a er thereof; wherein the pest infestation is caused by a population of pests comprising pesticide resistant pests.
In yet another aspect ofthe present invention, there is provided a method of controlling a population of pests sing ng a compound of formula (1) R1 R2 0 0 R3 R6 R4 R5 0 (I) wherein R1 is selected from —C(=O)R7, -OR8, -SR8, -C1-1ohydroxyalkyl, -NR9R10, - C(=N-R9)R7, -C(=N-OH)R7, -NO, -N02, -N(OR8)R7 and 8; R2 is selected from hydrogen, -C1-10alkyl, -C2-1oalkenyl, aryl and heteroaryl; R3, R4, R5 and R6 are each independently selected from hydrogen, -C1-10alkyl, -C3- 6cycloalkyl, alkenyl, —C1_10haloalkyl, —C1_10dihaloalkyl, —C1- lotrihaloalkyl, -0R8, -SRg, 0, -C(=N-R9)R7, -NO, -N02, -NR9OR8, -OSO3R8, -C1— laryl and —C(=O)R7; R7 is selected from hydrogen, -C1—1oalkyl, -C2-1oalkylaryl, oalkyl, -C2- loalkenyl, -C1-1oalkylheteroaryl, -C1-10haloalkyl, -C1-1odihaloalkyl, -C1_ lotrihaloalkyl, -C1-1ohaloalkoxy, hydroxyall 10nitroalkyl, -C1-3alkleC1—3alkyl, —C1-3alkleC1_3haloalkyl, —C1-3alkleC1- 3dihaloalkyl, -C1.3alkleC1-3trihaloalkyl, -OR8, -SR8 and —NR9R10; R8 is selected from hydrogen, -C1-10alkyl, -C2-1oalkylaryl, -C3-(,cycloalkyl, -C2- ioalkenyl, -C1-1oalkylheteroaryl, -C1_1ohaloalkyl, -C1_10dihaloalkyl, -C1- lotrihaloalkyl, -C1-1ohaloalkoxy, -C1-1ohydroxyalkyl, -C1_10thioalkyl and -C1-10nitroalkyl, R9 and R10 are independently selected from hydrogen, -C1-1oalkyl, alkylaryl, -C3_ 6cycloalkyl, -C2-10alkenyl, -C1-1oalkylheteroaryl, -C1-1ohaloalkyl, -C1-10dihaloalkyl, -C1_ lotrihaloalkyl, or a tautomer thereof; to an environment infested With or potentially infested With the population of pests; wherein the population of pests comprises pesticide resistant pests.
In a ?thher aspect of the present invention, there is provided a method of protecting stored plant part from pest infestation comprising contacting the plant part with a compound of formula (I) _ 5 _ R1 R2 0 0 R3 R6 R4 R5 0 (I) wherein R1 is selected from —C(=O)R7, -OR3, -SR8, -C1-1ohydroxyalkyl, -NR9R10, - C(=N-R9)R7, -C(=N-OH)R7, -NO, -N02, -N(OR8)R7 and —OSO3R8; R2 is ed from hydrogen, alkyl, -C2-1oalkenyl, aryl and heteroaryl; R3, R4, R5 and R6 are each independently selected from en, -C1-1oall 6cycloalkyl, -C2-10alkenyl, —C1-1ohaloalkyl, -C1-1odihaloalkyl, -C1_ lotrihaloalkyl, -0R8, -SR8, 0, -C(=N-R9)R7, -NO, -N02, -NR9OR8, 8, -C1- 10alkylaryl and —C(=O)R7; R7 is selected from hydrogen, -C1-1oalkyl, -C2-1oalkylaryl, oalkyl, -C2- 10alkenyl, -C1-1oalkylheteroaryl, -C1-10haloalkyl, -C1-1odihaloalkyl, -C1_ iotrihaloalkyl, -C1-1ohaloalkoxy, -C1-1ohydroxyall lonitroalkyl, -C1-3alkleC1.3alkyl, -C1-3alkleC1-3haloalkyl, -C1.3alkleC1- 3dihaloalkyl, -C1.3alkleC1-3trihaloalkyl, -OR8, -SR8 and —NR9R10, R3 is selected from en, -C1—10alkyl, alkylaryl, -C3-scycloalkyl, -C2— loalkenyl, -C1-1oalkylheteroaryl, haloalkyl, -C1-1odihaloalkyl, -C1_ iotrihaloalkyl, -C1-1ohaloalkoxy, -C1-1ohydroxyalkyl, -C1_10thioalkyl and -C1-10nitroalkyl, R9 and R10 are independently selected from hydrogen, -C1—1oalkyl, -C2-1oalkylaryl, -C3— 6cycloalkyl, -C2-10alkenyl, -C1-1oalkylheteroaryl, -C1-1ohaloalkyl, -C1-10dihaloalkyl, -C1_ lotrihaloalkyl, or a tautomer thereof. wherein the pest infestation is caused by a tion of pests comprising pesticide resistant pests.
Detailed description of the Invention Unless otherwise de?ned, all technical and scienti?c terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing ofthe present invention, preferred methods and als are described. For the purposes of the present invention, the following terms are defined below.
The articles "a" and "an" are used herein to refer to one or to more than one (i.e. to at least one) ofthe grammatical object of the article. By way of e, "an element" means one t or more than one t.
As used herein, the term "about" refers to a quantity, level, value, dimension, size, or amount that varies by as much as 30 %, 25 %, 20 %, 15 % or 10 % to a reference quantity, level, value, dimension, size, or amount.
Except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence ofthe stated features but not to preclude the presence or addition of r features in various embodiments of the invention.
It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia or any other country. id="p-16" id="p-16" id="p-16" id="p-16"
[0016] The term "combination" as used herein refers to the compound of a (I) and at least one second ide being used simultaneously in a single composition or separate compositions or sequentially in separate itions, such that the biological activity of each of the compounds in the insect overlaps or occurs at the same time. id="p-17" id="p-17" id="p-17" id="p-17"
[0017] The term "controlling" as used herein refers to preventing infestation with pests, repelling pests from an environment, ting, eradicating or ying pests, including increasing the mortality of the pests or inhibiting the growth and/or development of the pests or interrupting reproduction in the pests.
As used herein, the term "environment" refers to an environment in which the compound offormula (I) may be applied to ensure the pesticide resistant pest is exposed to the compound or to an environment in which the compound of formula (I) may be applied because it is a potential environment for infestation by a pesticide resistant pest. The environment may be an agricultural environment, a household environment, an rial environment or another environment that hosts or potentially 3O hosts the resistant pests. The agricultural environment includes environments for growing crops, trees or other plants of commercial importance that may be tible to a pesticide ant pest infestation. The agricultural environment includes not only the plant itself but also the soil and area around the plants as they grow, and areas where plants or parts of plants, for es, seeds, grains, leaves, roots or fruit, may be stored. The agricultural environment may also be an environment where a commercially important livestock animal is maintained, for example, a paddock, a barn, holding pens or milking sheds. A household environment includes environments inhabited by humans or animals such as companion animals and may include an indoor environment, such as carpets, curtains, cupboards, bed and bedding, animal beds or blankets, or the air inside a house. A household environment may also include an outdoor environment such as a domestic garden or an animal shelter such as a hutch or a kennel. An industrial environment includes environments which are used for industrial purposes such as manufacture, storage or vending or ts. Industrial environments include warehouses, manufacturing facilities, shops, storage facilities and the like, including pet shops, plant nurseries and grain storage facilities. Other environments may include leisure areas such as parks, stadiums, show grounds or water areas such as rivers, lakes, ponds or other places water may t or be slow moving or stagnant.
As used herein, the term " refers to a straight chain or branched saturated hydrocarbon group having 1 to 10 carbon atoms. Where appropriate, the alkyl group may have a specified number of carbon atoms, for example, C1-6alkyl which includes alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms in a linear or branched arrangement. Examples of suitable alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t—butyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 4—methylbutyl, n-hexyl, ylpentyl, 3-methylpentyl, 4- methylpentyl, 5-methylpentyl, lbutyl, 3-ethylbutyl, heptyl, octyl, nonyl and decyl. id="p-20" id="p-20" id="p-20" id="p-20"
[0020] As used herein, the term "alkenyl" refers to a straight-chain or branched hydrocarbon group having one or more double bonds between carbon atoms and having 2 to 10 carbon atoms. Where appropriate, the alkenyl group may have a specified number of carbon atoms. For example, C2-C6 as in "Cz-Csalkenyl" es groups having 2, 3, 4, 5 or 6 carbon atoms in a linear or branched arrangement. Examples of 3O suitable l groups e, but are not limited to, ethenyl, yl, isopropenyl, butenyl, enyl, pentenyl, pentadienyl, hexenyl, hexadienyl, heptenyl, l, nonenyl and decenyl.
As used herein, the term "cycloalkyl" refers to a saturated cyclic hydrocarbon. The cycloalkyl ring may include a speci?ed number of carbon atoms.
For example, a 3 to 6 membered cycloalkyl group includes 3, 4, 5 or 6 carbon atoms.
Examples of suitable cycloalkyl groups include, but are not limited to, ropyl, cyclobutyl, cyclopentyl and cyclohexyl.
As used herein, the term "aryl" is intended to mean any stable, clic, ic or tricyclic carbon ring system of up to 7 atoms in each ring, wherein at least one ring is aromatic. Examples of such aryl groups include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, yl, phenanthrenyl, biphenyl and thyl.
The term "heteroaryl" as used herein, represents a stable monocyclic, bicyclic or tricyclic ring of up to 7 atoms in each ring, n at least one ring is ic and at least one ring contains from 1 to 4 heteroatoms selected from the group consisting of O, N and S. Heteroaryl groups within the scope of this de?nition include, but are not limited to, acridinyl, carbazolyl, cinnolinyl, quinoxalinyl, quinazolinyl, pyrazolyl, indolyl, isoindolyl, lH,3H-l-oxoisoindolyl, benzotriazolyl, furanyl, thienyl, thiophenyl, benzothienyl, benzofuranyl, benzodioxane, benzodioxin, quinolinyl, isoquinolinyl, oxazolyl, isoxazolyl, imidazolyl, nyl, pyridazinyl, pyridinyl, dinyl, pyrrolyl, tetrahydroquinolinyl, thiazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4- triazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,5-triazinyl, 1,2,4-triazinyl, l,2,4,5-tetrazinyl and tetrazolyl. Particular heteroaryl groups have 5— or 6-membered rings, such as pyrazolyl, furanyl, thienyl, oxazolyl, indolyl, isoindolyl, lH,3H-loxoisoindolyl , isoxazolyl, imidazolyl, pyrazinyl, pyridazinyl, nyl, pyrimidinyl, yl, lyl, isothiazolyl, triazolyl, 1,2,4-triazolyl and 1,2,4-oxadiazolyl and 1,2,4—thiadiazolyl.
The term "haloalkyl" as used herein refers to an alkyl group in which one or more hydrogen atoms of the alkyl group is replaced with a halo atom. Where appropriate, the alkyl group may have a speci?ed number of carbon atoms, for example, C1-6haloalkyl which includes haloalkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms in 3O a linear or branched arrangement. Examples of haloalkyl groups include ?uoromethyl, di?uoromethyl, tri?uoromethyl, l-?uoroethyl, 2-?uoroethyl, l,l-di?uoroethyl, 2,2- ?uoroethyl, l,l,2-tri?uoroethyl, 2,2,2-tri?uoroethyl, 3-?uoropropyl, 3,3-di?uoropropyl, 3,3,3-tri?uoropropyl, 4-?uorobutyl, 4,4-di?uorobutyl, 4,4,4—tri?uorobutyl, 5— ?uoropentyl, 5,5-di?uoropentyl, tri?uoropentyl, 6-?uorohexyl, 6,6-di?uorohexyl or 6,6,6-tri?uorohexyl, chloromethyl, dichloromethyl, trichloromethyl, l-chloroethyl, 2-chloroethyl, l,l-dichloroethyl, 2,2-chloroethyl, 1,1,2-trichloroethyl, 2,2,2- oroethyl, 3-chloropropyl, 3,3—dichloropropyl, trichloropropyl, 4-chlorobutyl, 4,4-dichlorobutyl, 4,4,4-trichlorobutyl, 5-chloropentyl, 5,5-dichloropentyl, 5,5,5- trichloropentyl, 6—chlorohexyl, chlorohexyl or 6,6,6-trichlorohexyl, bromomethyl, dibromomethyl, tribromomethyl, l-bromoethyl, 2-bromoethyl, 1,1-dibromoethyl, 2,2- dibromoethyl, 1,1,2-tribromoethyl, 2,2,2-tribromoethyl, 3-bromopropyl, 3,3— dibromopropyl, 3,3,3-tribromopropyl, 4-bromobutyl, 4,4-dibromobutyl, 4,4,4- tribromobutyl, 5-bromopentyl, 5,5—dibromopentyl, 5,5,5-tribromopentyl, ohexyl, 6,6-dibromohexyl or 6,6,6-tribromohexyl and the like.
"Halo" as used herein refers to ?uoro, chloro, bromo and iodo.
The terms "hydroxyalkyl", "thioalkyl" and "nitroalkyl" each refer to an alkyl group as de?ned above in which one hydrogen atom has been replaced by a yl group, a thiol group or a nitro group respectively.
The term "alkoxy" as used herein refers to an oxygen substituent that is substituted with an alkyl group as de?ned above. Examples of suitable alkoxy groups include, but are not limited to, -OCH3, -OCH2CH3, —O(CH2)2CH3, - OCH(CH3)2, -O(CH2)3CH3, -OCH2CH(CH3)2, -OC(CH3)3, -O(CH2)4CH3 and -O(CH2)5(CH3).
The compounds of formula (I) may exist in a number of tautomeric forms.
For example, tautomerism is shown in the scheme below: 0 R O R HO R HO O O O O l l O O O id="p-29" id="p-29" id="p-29" id="p-29"
[0029] It is intended that all such tautomeric structures are included with in the scope of formula (I).
It is also possible that the nds for formula (I) may exist in isomeric form. The compounds may be enantiomers or diastereomers and may be present as an individual isomer or in mixture form, including c mixtures.
By "pesticide resistant pest", it is meant a pest such as an insect or arachnid that has developed resistance to one or more pesticides that have previously been used to control them. The pesticide resistant pest may be present in a population of pests.
For example, the Tiaro strain of R. lus has a ance pro?le of about 30% ?uozuron, 60.6% cypermethrin, 57.6% ?umetron, 16.2% amitraz (amidine), 11.3% DDT, 9.3% chlorpyrifos and 2.4 % dieldrin ance.
Method ofthe invention In one aspect, the present invention provides a method of controlling a pesticide resistant pest comprising exposing the ide resistant pest to a compound of formula R1 R2 0 0 R3 R6 R4 R5 0 (I) wherein R1 is selected from —C(=O)R7, -OR8, -SR8, -C1-1ohydroxyalkyl, -NR9R10, - C(=N-R9)R7, -C(=N-OH)R7, -NO, —N02, -N(OR8)R7 and —OSO3R8; R2 is selected from hydrogen, -C1-1oalkyl, -C2-1oalkenyl, aryl and heteroaryl; R3, R4, R5 and R6 are each independently selected from hydrogen, -C1-1oalkyl, -C3_ 6cycloalkyl, -C2_10alkenyl, -C1_10haloalkyl, -C1_10dihaloall lotn'haloalkyl, -OR8, -SR8, -NR9R10, -C(=N—R9)R7, —NO, -N02, -NR9OR8, -OSO3R8, -C1— malkylaryl and —C(=O)R7; R7 is selected from hydrogen, -C1-10alkyl, -C2-1oalkylaryl, Cmcycloalkyl, -C2- loalkenyl, alkylheteroaryl, haloalkyl, -C1-1odihaloalkyl, -C1_ 10trihaloalkyl, haloalkoxy, -C1-1ohydroxyalkyl, -C1-1othioalkyl, —C1_ lonitroalkyl, -C1-3alkleC1.3alkyl, -C1-3alkleC1-3haloalkyl, -C1.3alkleC1- 3dihaloalkyl, -C1.3alkleC1-3trihaloalkyl, -OR8, -SR8 and —NR9R10, R8 is selected from hydrogen, -C1-ioalkyl, -C2-1oalkylaryl, -C3-6cycloalkyl, -C2- nyl, -C1-10alkylheteroaryl, -C1-1ohaloalkyl, -C1-1odihaloalkyl, -C1_ lotrihaloalkyl, haloalkoxy, -C1-1ohydroxyalkyl, -C1_1othioalkyl and -C1_10nitroalkyl; R9 and R10 are independently selected from hydrogen, -C1-1oalkyl, alkylaryl, -C3— scycloalkyl, -C2_10alkenyl, -C1-1oalkylheteroaryl, haloalkyl, -C1-10dihaloalkyl, -C1- 10trihaloalkyl; or a er thereof.
In some embodiments, the compound of formula (I) is a compound of a 0 O O (11) wherein R11 is selected from —CR12R13R14 or —NR15R16; one of R12 and R13 is en and the other is hydroxyl or —OCR17R18R19 or R12 and R13 together form an oxo group (=0) or a =N-OH group; R14 is —CH(CH3)CR20R21R22, -CH2CH(CH3)CR20R21R22 or —CH(CH3)CH2CR20R21R22; R15 and R16 are independently selected from hydrogen and C1-1oalkyl; R17, R18 and R19 are ndently selected from hydrogen or halo; and R20, R21 and R22 are independently selected from hydrogen, hydroxyl, halo, N02 and — -OCR17R18R19; or a tautomer thereof. id="p-34" id="p-34" id="p-34" id="p-34"
[0034] In some embodiments, the compound of formula (I) is a compound of formula (III): 0 (III) wherein one of R23 and R24 is hydrogen and the other is hydroxyl or —OCR27R28R29 or R23 and R24 together form an oxo group (=0); R25 is —CR30R31R32, -CH2CR30R31R32 or 3)CR30R31R32; R26 is H or —CH3; wherein where R26 is H, R25 is —CH(CH3)CR30R31R32; R27, R28 and R29 are independently selected from hydrogen or halo; and R30, R31 and R32 are independently selected from hydrogen, hydroxyl, halo, N02, and -OCR5R6R7; or a tautomer thereof.
In some embodiments, the compound offonnula (I) is selected from: CCI3 CHCI2 CHZCI CBr3 O O O o O O O O O O O O O O O O CHBr2 CHzBr CHZOH g o o o o o o o o o o o o o o o o CH2OCF3 CHZSH CH2N02 o o o O O o o o o o o o o o [LR H‘NL H3C‘NJ\ HO\NJ\ O o 09¢?) 03??) 03??) CHCIZ CH2C| OBI-3 N N N o o o o CF3 CHFZ CH2F o o o o o o o o o o o o o o o o CHBr2 CHZBr CHZOH 3 o o o o o o o o o o o o o o o o O O O O O O O O o O O or a tautomer thereof. id="p-36" id="p-36" id="p-36" id="p-36"
[0036] In particular embodiments, the compound of formula (I) is selected from ?avesone (l-isobutyroyl—3,3,5,——5tetramethylcyclohexane—2,4,6-trione): leptospermone (l-Valeroyl-3,3,5,5-tetramethylcyclohexane-2,4,6-trione): 1 O or isoleptospermone (l-isovaleroyl—3 ,3 ,5 ,5—tetramethylcyclohexane—2,4,6-t1ione): especially ?avesone.
The compounds of a (I) may be isolated from oil bearing trees such as trees from the Myrtaceae family such as spermum scoparium or Eucalyptus grandis 0r Eucalyptus cloezz'ana, especially Leprospermum scoparium.
In other embodiments, the compound of formula (I) may be prepared synthetically, for example, as described in ) 3 3 trihydroxybenzene may be reacted with RCN in the presence of zinc de (Blatt, Org. Synth. Col 11, 1943, 522-523) as shown in Scheme 1: OH OH O —> R HO OH HO OH Scheme 1 Anhydrous methyl iodide (6 Eq) is slowly added to the l-acyl-2,4,6- trihydroxybenzene (1 eq) and sodium ethoxide (6 eq) in anhydrous ol as shown in Scheme 2 to afford the -3,3,5,5-tetramethyl-2,4,6-cyclohexatrione (US 4,202,840).
GHQ 00 (3% R HO OH 0 0 Scheme 2 The effective amount of compound of formula (I) will depend on whether the compound is being applied to the pests themselves or to an environment or livestock animal or companion animal or a plant part and will also depend on the identity ofthe pesticide resistance pest. Typically, an ive amount will fall within the range of 0.1 ppm to about 500,000 ppm, especially 1 to 200,000 ppm or 1 to 100,000 ppm. In some embodiments where direct exposure of the pest to the compound of formula (1) occurs, the effective amount may be in the range of 10 and 10,000 ppm or 100 and ,000 ppm or 100 and 5000 ppm, especially 300 and 5000 ppm or 500 and 5000 ppm, more especially 800 ppm to 2,500 ppm or 900 ppm to 2,000 ppm. In some embodiments, the effective amount may be between 100 and 1000 ppm, for e, 200 to 800 ppm or 300 to 600 ppm. In other embodiments, the effective amount may be between 600 and 5000 ppm, especially 1000 and 2500 ppm. In some embodiments, the ive amount is between 20 and 100 ppm, especially 25 and 80 ppm. An effective amount to apply to an environment, such as grain in a grain store, may be in the range of 20 ppm to 100 ppm, especially 50 ppm to 100 ppm.
In some embodiments, the pests are insects that are resistant to one or more icides. In other embodiments, the pests are ids that are resistant to one or more arachnicides. In some embodiments, the pests are a population of insects comprising insects resistant to one or more insecticides or a population of arachnids comprising arachnids resistant to one or more arachnicides.
The insects or populations of insects comprising insects ant to one or more insecticides e insects such as: (a) from the order of the lepidopterans (Lepidoptera), for example, Adoxophyes orana, Agratis ipsz'lon, Agron's segetum, Alabama argz'llacea, Anticarsia gemmatalz's, Argyresthia conjugella, Autographa gamma, Cacoecia murmana, Capua reticulana, Choristoneura?tmzferana, Chilo partellus, Choristoneura ntalz's, Cirphis um'puncta, Cnaphalocrocis medmalz's, Crocidolomia binotalz‘s, Cydz‘a pomonella, Dena’rolimus pini, Diapham'a mn'dalz's, Diatraea grandiosella, Earias insulana, Elasmopalpus lignosellus, Eupoecilia ambiguella, Feltia subterranea, Grapholiz‘ha funebrana, Grapholz'tha molesta, Heliocoverpa armigera, Heliocoverpa ens, Heliocoverpa zea, Hellula undalis, Hibernia defoliaria, Hyplz'amria cunea, Hyponomeuta malmellus, Keiferia lycopersz'cella, Lambdmafzscellaria, Laphygma exigua, Leucoptera scitella, Lithocollen's blancara’ella, Lobesia botrana, Loxosz‘ege sticn'calis, Lymam‘ria dispar, Lymanm'a monacha, Lyone?a lz’a, Manduca sexta, soma neustria, Mamestra brassicae, Mocis repana’a, Operophthera brumata, Orgyia pseudotsugara, Ostrim'a nubilalz's, Pandemis heparana, Panolz's?amnea, 3O Pec?nophora gossypiella, th‘horimaea operculella, Phyllocmsn's citrella, Pieris brassz'cae, Plathypena scabra, Plazynota stultana, Plutella xylostella, Prays citri, Prays oleae, Prodem'a sum'a, 'a ornithogalli, Pseudoplusia includens, Rhyacz‘om'a ?usrrana, Scrobipalpula absoluta, Sesamia inferens, Sparganorhis pillerz'ana, Spodoptera?ugiperda, Spodoptera littoralz's, Spodopz‘era , ta derogata, Synanthedon myopaeforinis, Thaumaropoea pityocampa, 'x viridana, Trichoplusia m', Tryporyza incerl‘ulas and Zeiraplzera canadensis, also Galleria mellonella, Sitotroga cerealella, Ephestz'a cautella and Tineola bisselliella; (b) from the order of the beetles (Coleoptera), for example, Anthonomus grandis, Anthonomus pomorum, Apion vorax, z'a linearis, Blastophagus pimperda, Cassida nebulosa, Cerotoma caz‘a, Ceuz‘lzorhynchus assimilis, Ceuthorhynchus napi, Chaerocnema is, Conoderus vespern'nus, Criocerz's asparagz', Cryptolestes ineus, Dendroctonus ru?pennis, Diabron'ca longicomis, Diabroz‘ica punctata, Diabrot‘ica era, Epilaclma varivesn's, Epirrz'x hirn'pennis, Eutinoborhrus brasiliensis, Hylobz'us 's, Hypera brurmeipennis, Hypera postica, Ips typographus, Lema bilineara, Lema melanopus, Lepn'notarsa decemlineata, Limom'us caliform'cus, Lissorhoptrus oryzophilus, Melanoz‘us communis, Meligethes , Melolontlza hippocasz‘ani, Melolontlza melolom‘lza, Oulema oryzae, ynchus sulcatus, Oliorhynchus ovatus, Phaedon cochleariae, Phylloperz‘ha hor?cola, Phyllophaga s11, Phyllotreta chrysocephala, Phyllotreta nemorum, Phyllotreta striolata, Papillia japom'ca, Psylliodes napi, Scolytus intricatus and Sitona lineaz‘us, also Bruchus ru?manus, Bruchus pisorum, Bruclzus lenzis, zilus granarz'us, Lasz'oclerma serricome, Oryzaephilus surinamensis, Rhyzopertha dominica, ilus oryzae, Tribolium castaneum, Trogoclerma granarium and Zabrotes subfasciatus; (c) from the order of the dipterans (Diptera), for example, Anastrepha ludens, Ceralitz's capitata, Contarim'a sorghz'cola, Dacus cucurbitae, Dacus oleae, Dasz'neura brassicae, Delia coarctata, Delia radicum, Hydrellia griseola, Hylem'yia platura, Liriomyza sativae, Liriomyza trifolz'z', Mayez‘z'ola destructor, Orseolia oryzae, Oscinella frit, Pegomya hyoscyami, Phorbia an?qua, Phorbia brassicae, Phorbia coarcz‘az‘a, Rhagoletis cerasi and Rhagole?s pomonella, also Aecles aegyp?, Aedes vexans, Aedes albopictus, Anopheles maculipennis, Chrysomya bezziana, Cochliomyia hominivorax, Chrysomya macellaria, Cordylobia anthropophaga, Culex pipiens, Fannia canicularis, 3O Gasterophilus intestinalis, Glossma morsitans, Haematobia irritans, iplosis ris, rma lineata, Lucilz'a cuprina, a ta, Musca domes?ca, Muscina stabulcms, Oestrus ovis, Tabanus bovinus and Simulium damnosum; (d) from the order of the thrips (Thysanoptera), for example, Frankliniez’lafusca, Frankliniella occidentalis, iniella tritici, Haplothrips tritici, Heliothirips rhoidalis, Scirtothrips citri, Thrips oryzae, Thrips palmz' and Thrips tabaci; (e) from the order of the hymenopterans (Hymenoptera), for example, Athalia rosae, Atta cephalores, Atta sexdens, Aria texana, Hoplocampa minuta, Hoplocampa inea, Iridomyrmex humilis, Iridomyrmex purpureus, Monomorium pharaonis, Solenopsis geminata, Solenopsis invicta, Solenopsis richteri and Technomyrmex albipes; (f) from the order of the heteropterans (Heteroptera), for example, Acrosternum hilare, s leucopterus, Cyrtopelz‘is notatus, Dysdercus cingulatus, Dysdercus inrermedius, Eurygasrer integriceps, Eusckl'srus icterz'cus, Leproglossus phyz’lopus, Lygus us, Lygus lineolaris, Lygus sis, ea pic?vem‘ris, Nezara viridula, Piesma quadrata, Solubea insularl's and ?zyanm perdiror; (g) from the order of the homopterans tera), for example, Acyrthosiphon onobryckis, Acyrthosiphon pisum, Adelges larz'cz's, Aonidielfa auramz'i, Aphidula nasturtii, Aphisfabae, Aphis ii, Aphis pomi, Aulacorthum soiani, Bemisia tabaci, Brachycaudus carduz', Brevicoryne brassicae, Dalbulus maidis, Dreyfusia nordmannicmae, Drey?wia piceae, Dysaphz‘s radicola, Empoascafabae, rna lam'gerum, phax ella, Macrosiphum avenae, Macrosz'phun euphorbiae, Macrosiphon rosae, Megoura viciae, Metopolophium um, Myzus persicae, Myzus cerasz', Nephotettix cincticeps, Niz’aparvata lugens, Perkinsiella saccharicida, Phorodon humuli, Psylla mali, Psylla pyri, Psylla pyricola, Rhopalosiphum maidis, Schizaphis gramz'num, Sitobion avenae, lla?trcifera, Toxoptera citricida, Trialeurodes abutilonea, Triaieurodes vaporariorum and Viteus vitifoliae; (h) from the order of the es (Isoptera), for example, Kalotermes?avicollis, Coptotermes spp, Leucotermes?avipes, Macrotermes subhyalinus, Macrotermes darwiniensz's, Mastotermes spp., A/Iicrotermes spp, Nasun'termes spp such as termes i, Odontotermesformosanus, Reticulitermes lucifugus and Termes natalensis; 3O (i) from the order of the orthopterans (Orthoptera), for example, Gryllotalpa gryllotalpa, Locusta migratorz'a, Melanoplus bivz'ttatus, Melanoplusfemurrubrum, Melanopius mexicanus, Melanopius sanguim'pes, Melanoplus spretus, Nomadacris Sepremfasciara, Schisrocerca americana, Schisrocerca peregrina, Stauronotus maroccanus and Schistocerca gregaria, also Acheta domesticus, Blatta orientalis, Blarrella germanica and Periplaneta americana; (i) from the order of the phthirapterans (Phthiraptera), for example, Mallophaga, such as Damalina spp., and Anopz’ura such as Linognarhus and Haemaropinus spp, ; (k) from the order of the hemnipterans (Hemiptera), for example, Aphis, Bemm'sia, Phorodon, Aeneolamz'a, Empoasca, Perkinsiella, Pyrilla, Aonidz'ella, Coccus, Pseudococcus, Helopeln's, Lygus, cus, Oxycarenus, Nezara, des, Triaroma, Psylla, Myzus, Megoura, Phylloxera, Adelges, Nilaparvata, Nephotem'x 0r Cimex spp. ; (1) from the order of the siphonapterans (Siphonaptera), for example, Ctenocephalides 0r Pulex spp., (m) from the order of the thysanurans (Thysanura), for example, Lepisz'na spp. ; (n) from the order of the dermapterans (Dermaptera), for example, Forfzcula spp. ; and (o) from the order of the psocopterans (Psocoptera), for example, Peripsocus spp.
The insects may be resistant to one or more insecticides ly used to control the insect before resistance develops. For example, the insects may be resistant to one or more icides selected from: (i) sodium channel modulators such as a pyrethroid, DDT and methoxychlor.
Suitable pyrethroids include acrinathrin, allethrin, bifenthrin, bioallethrin, bioallethrin-S-cyclopentyl, bioresmethrin, cycloprothrin, cy?uthrin, [3- rin, cyhalothrin, y-cyhalothrin, lothrin, cypennethrin, oc-cypermethrin, B-cypermethrin, G-cypermethrin, rmethrin, cyphenothrin, deltamethrin, dime?uthrin, empenthrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, rinate, ?umethrin, nate, tau-?uvalinate, prox, imiprothrin, meto?uthrin, pennethrin, phenothrin, prallethrin, pro?uthrin, pyrethrin (pyrethrum), resmethrin, RU15525, ofen, te?uthrin, tetramethrin, tralomethrin, trans?uthrin 3O and ZX l 890 1. (ii) acetylcholinesterase (AChE) inhibitors such as a carbamate or an organophosphate. Suitable ates include alanycarb, aldicarb, bendiocarb, acarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, carb, methiocarb, methomyl, metolcarb, oxamyl, carb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb and xylylcarb. Suitable organophosphates include acepahte, azamethiphos, azinphos, azinphos-methyl, azinphos-ethyl, cadusafos, chlorethoxyfos, chlorfenvinfos, chlormephos, chlorpyrifos, chlorpyrifos-methyl, coumaphos, hos, demeton-S-methyl, diazinon, dichlorvos, dicrotophos, dimethoate, dimethylvinphos, disulfoton, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, isofenphos, isoxathion, malathion, mecarbam, methamidophos, methidathion, hos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos, phos—methyl, profenfos, propetamphos, prothiofos, pyraclofos, phenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, rfon and vamidothion. (iii) GABA-gated chloride channel nists such as an organochloride or a ?prole. Suitable organochlorides include chlordane, endosulfan and oc- enosulfun. Suitable s include ethiprole, l, prole, and pyriprole. (1V) nergic acetylcholine receptor agonists such as nicotine or a chloronicotinyl compound. le chloronicotinyl compounds include acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiocloprid and thiamethoxam.
(V) allosteric acetylcholine receptor modulators such a spinetoram or spinosad. (vi) chloride channel actuators such as abamectin, emamectin benzoate, lepimectin or milbemectin.
(Vii) le hormone mimics selected from hydroprene, kinoprene, methoprene, S—methoprene, fenoxycarb or pyriproxyfen. (viii) homopteran feeding blockers such as pymetrozine or ?anicamid. (1X) mitochondrial ATP se inhibitors such as diafenthiuron or tetradifan.
(X) uncouplers of oxidative phosphorylation such as chlorfenapyr or DNOC. (xi) nicotinic acetylcholine or channel blockers such as bensultap, cartap hydrochloride, thiocyclam or thiosultap—sodium. (xn) inhibitors of chitin biosynthesis such as a benzoylurea or buprofezin.
Suitable benzoylureas include bistri?uron, chlor?uazuron, di?ubenzuron, ?ucycloxuron, ?ufenoxuron, hexa?umuron, lufenuron, novaluron, novi?umuron, pen?uron, te?ubenzuron or tri?umuron. (xn? moulting disruptors such as cyromazine. (xiv) ecdysone receptor agonists or disruptors such as a hydrazine. le diacylhydrazines include chromafenozide, halofenozide, methoxyfenozide or tebufenozide.
(XV) octopamine receptor agonists such as amitraz. (xvi ) ondrial complex I electron transport inhibitors such as hydramethylnon, acequinocyl and ?uacrypryrim. (xvi i) acetyl CoA carboxylase inhibitors such as a tetronic acid derivative or a tetramic acid derivative. Suitable tetronic acid derivatives include iclofen and spiromesfen and a le tetramic acid derivative is spirotetramat. (xviii) voltage-dependent sodium channel blockers such as indoxacarb or meta?umizone. (xix) mitochondrial complex IV on inhibitors such as a phosphine or cyanide. Suitable phosphines include zinc ide, ium phosphide, calcium phosphide or phosphine.
(XX) mitochondrial x IV electron transport inhibitors such as cyenopyrafen. (xxi) ryanodine receptor modulators such as chloranthraniliprole, cyantraniliprole and ?ubendiamide.
The arachnid populations include spiders, daddy long legs, scorpions, pseudoscorpions, microscopions, mites and ticks, especially mites and ticks (Acarina).
Suitable arachnids e: (i) Mites such as Aculops Eycopersicae, Aculops pelekassi, Aculus Schlechz‘endali, Balustium medicagoense, Brevipalpus pkoenicis, Brevipalpus caliform'cus, Bryobia praetiosa, Bryobia rubrioculus, Bryobia spp such as clover mite, Dermanyssus gallinae, Eatetranychus carpini, Eatetranichus z', Euterranychus banksz'a, Eutetranychus orientalz's, yes m', Eryophyes tiliae, yes inangulis, Eriophyes vitis, Halotydeus destrucror gged earth mite), Oligonychus pratensz's, 011'gonychus co?eae, Oligom'tis oryzae, 011'gonychus milferi, Panonychus ulmi, Panonychus citri, Penrhaleus Spp such as Blue oat mite Phyllocoptmta oleivora, Polyphagotarsonemus latus, Psoroptes ovis, Sarcoptes scabiei, Tarsonemus pallidus, Tetranychus cinnabarinus, Terranychus kanzawai, Tetranychus paci?cus and Tetranychus ur?cae. (ii) Ticks such as mma americanum, Amblyomma variegarum, Argas persicus, Boophilus annulatus, Boophilus decoloraz‘us, Boophilus miccroplus, Dermacem‘or silvarum, Hyalomma truncatum, Ixodes ricinus, Ixodes ndus, Ornithodorus moubaz‘a, Otobius ', Rhipicephalus culatus, Rhipz'cephalus i and Rhipicephalus microplus.
The Arachnids may be resistant to one or more arachnicides commonly used to control the arachnid, especially mites or ticks, before resistance develops. For example, the arachnids may be resistant to one or more of the arachnicides or acaricides selected from abamectin, acequinocyl, acrinathrin, rb, alpha-cypennethrin, amidithion, amiton, amitraz, aramite, arsenous oxide, azinphos-ethyl, os-methyl, azobenzene, azocyclotin, azothoate, benomyl, benzoximate, benzylbenzoate, bifenazate, bifenthrin, binapacryl, bromocyclen, bromophos, bromophos-ethyl, bromopropylate, butocarboxim, camphechlor, carbanolate, carbaryl, carbofuran, carbophenothion, carvacrol, chinomethionat, chlorbenside, chlordimeform, chlorfenapyr, chlorfenethol, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorobenzilate, chloromebuform, chloromethiuron, chloropropylate, chlorpyrifos, chlorthiophos, clofentezine, closantel, coumaphos, crotamiton, crotoxyphos, cyanthoate, cycloprate, cyenopyrafren, cy?umetofen, thrin, tin, ethrin, cyromazine, DDT, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, n-S-methyl, 3O diafenthiuron, dialifos, diazinon, dichlo?uanid, dichlorvos, dicofol, dieldrin, dienochlor, di?ovidazin, dimefox, dimethoate, dinex, dinobuton, dinocap, dinocton, nton, dinosulfon, dinoterbon, dioxathion, diphenyl sulfone, disulfoton, DNOC, endosulfan, endothion, ethion, ethoate-methyl, etoxazole, fenaza?or, fenazaquin, fenbutatin oxide, fenothiocarb, pathrin, fenpyroximate, fenson, fentrifanil, fenvalerate, il, ?uacrypyrim, ?uazuron, ?ubenzimine, ?ucycloxuron, ?ucythrinate, ?uenetil, ?ufenoxuron, ?umethrin, ?uorbenside, nate, formetanate, fonnothion, forrnparanate, genit, halfenprox, heptenophos, hexachlorophene, hexythiazox, bophos, lindane, malathion, mecarbam, methacrifos, methamidophos, methiocarb, metolcarb, mevinphos, milbemectin, mipafox, monocrotophos, naled, dide, omethoate, oxamyl, oxydeprofos, oxydisulfoton, parathion, permethrin, phenkapton, phorate, phosalone, phosmet, phoxim, pirimiphos— methyl, propargite, propetamphos, propoxur, prothidathion, prothoate, ben, pyrimidifen, quinalphos, quintiofos, schradan, sophamide, spirodiclofen, amid, sulfotep, sulfur, tau-?uvalinate, tebufenpyrad, TEPP, tetrachlorvinphos, tetradifon, tetrasul, thiocarboxime, thiofanox, ton, thioquinox, thuringiensin, thene, triazophos, trichlorfon and vamidothion. id="p-46" id="p-46" id="p-46" id="p-46"
[0046] The pest may be in any part of its life cycle, for example, an egg, , pupa, adult or nymph. In some embodiments, the pest may be in larval form.
In particular embodiments, the pest is a tick or a mite, especially a tick or a mite in larval form, especially a cattle tick in larval form.
In some embodiments, the method ofthe invention is a method of treating or preventing a pest infestation in a livestock animal or a companion animal, wherein the pest infestation is caused by a tion of pests comprising pesticide resistant pests.
The method involves applying a compound of formula (I) as de?ned above to the livestock animal or companion animal.
In some embodiments, the livestock animal is selected from cattle, sheep, goats, deer, pigs, camels, llamas, alpacas, chickens and the like. In other embodiments, the companion animal is selected from a dog, cat, rabbit, guinea pig, r, mouse, horse, and the like.
In some embodiments, the compound offormula (I) is applied topically, for example by dipping, spraying, pour-on, washing, fogging or misting, drenching or 3O droplet application. In other embodiments the compound of formula (I) is applied systemically, for example, in a tablet, capsule, chewable tablet or liquid drench formulation.
In some embodiments, the method is for controlling a pest infestation or potential pest infestation in an environment, wherein the pest ation is caused by a population of pests comprising pesticide resistant pests. The method involves applying a compound of formula (I) as defined above to the environment hosting the pest infestation or at risk of hosting a pest infestation, The environment may be any environment that may host a pest infestation, for example, an agricultural environment, a household environment, an industrial environment or a e environment. In particular embodiments, the environment is an agricultural environment.
In some embodiments, the method is used to l pests that infest stored plant products. The method involving contacting the plant t with a compound of formula (I).
Suitably, the plant part that is to be protected is contacted by dipping, spraying, fogging or misting. The contact may be achieved prior to or during storage, especially prior to storage. id="p-54" id="p-54" id="p-54" id="p-54"
[0054] In some embodiments, the plant part is grain that is to be stored before use, for example, in a silo. This method may be particularly useful for controlling pests that damage grain in storages, where the population of pests ses pesticide resistant pests, for example, populations ofRhyzoperz‘ha dominica, Sitophilus oryzae, Tribolium eum, Oryzaephilus surinamensis or Cryptolestesfermgz'neous including pests resistant to organophosphates such a fenitrothion, malathion, chlorpyrifos-methyl and pirimiphos-methyl; and/or synthetic pyrethroids such as deltamethrin or bioresmethrin; and/or insect growth regulators such a methoprene.
In some embodiments, the method is used to control pests that infest crops and cause damage, especially grain crops, such as rice, wheat, durum wheat, corn, maize, barley, millet, sorghum, oats, rye, triticale, teff, fonio, wild rice and spelt. The method es contacting the pest with a compound of a (I) in an agricultural environment. The contact may be made by ng the compound or a ition comprising a compound of formula (I) to a crop and/or the soil nding the crop, where the crop is infested with the pest or is likely to become infested with the pest, 3O particularly a population of pests that includes pesticide resistant pests. Examples of pesticide resistant pests e populations ofH. destructor (Redlegged earth mite), Balustium medicagoense, leus spp such as Blue oat mite and Bryobia spp such as clover mite that are resistant to organophosphates such as chlorpyrifos and/or pyrethroids such as bifenthrin.
While in some embodiments, the nd offormula (I) may be applied neat, in particular embodiments, the compound of formula (I) is applied in the form of a ition together with able carriers, diluents and/or excipients. This also applies to re of the pests to the compound of formula (I).
The composition may be ated into any suitable composition such as a spray, aerosol, oil, emulsi?able concentrate, le powder, ?owable formulation, granulated formulation, powder, dust, solution, suspension, emulsion or controlled release formulation, tablet, capsule, oral liquid formulation, shampoo, conditioner, spot- on formulation, drench or dip. The composition may be formulated with solid or liquid carriers as appropriate. The choice of formulation and mode of application will depend on the pest being controlled, the environment it is being controlled in or the animal which is ed by the pest, and appropriate selection will be made with consideration of pest, subject and environment.
In some embodiments, the ation may contain naturally occurring ve, such as antioxidants and stabilizers. For example, idants may include OL- tocopherol, and suitable stabilizers may include gum arabic, guar gum, locust bean gum, xanthan gum, , polyvinyl alcohol, sodium caseinate and mixtures thereof. id="p-59" id="p-59" id="p-59" id="p-59"
[0059] Examples of solid carriers useful in preparing the formulations are clays including kaolin clay, diatomite, water-containing synthetic silicon oxide, bentonite, Fubasami clay, and acid clay, talcs; ceramics, inorganic minerals such as CeliteTM, quartz, sulfur, active carbon, calcium carbonate and ed silica; these solid carriers being ?nely divided or granular. Examples of use?il liquid carriers are water, alcohols such as methanol and ethanol, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene and methylnaphthalene, aliphatic hydrocarbons such as hexane, cyclohexane, ne and light oil, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and isobutyronitrile, ethers such as ropyl ether and dioxane, acid amides such as N,N- 3O dimethylforrnamide and N,N—dimethylacetamide, halogenated hydrocarbons such as dichloromethane, trichloroethane and carbon tetrachloride, dimethyl ide, and fish oils, mineral oils, plant derived oils such as olive oil, canola oil, cotton-seed oil, soybean oil and sesame oil as well as essential oils such as lavender oil, ptus oil, tea tree oil, citrus oil etc. Solid or liquid carriers can be used alone or in combination.
Examples ofgas carriers, those of propellants, are butane gas, isobutene, pentane, LPG (lique?ed petroleum gas), dimethyl ether, ?uorocarbons and carbon dioxide gas.
Examples of surfactants are alkylsulfuric acid esters, alkylsulfonic acid salts, alkylarylsulfonic acid salts, alkyl aryl ethers and polyoxyethylene adducts thereof, polyethylene glycol ethers, polyhydric alcohol esters, sugar l derivatives, sorbitane monolaurate, alkylallyl sorbitane monolaurate, alkylbenzene sulfonate, alkylnaphthalene sulfonate, lignin sulfonate, and ic acid ester salts of higher alcohols. These surfactants may be used alone or in combination.
Examples of adjuvants for the formulations, such as binders and dispersants, are casein, gelatin, polysaccharides such as starch, gum arabic, cellulose derivatives and alginic acid, lignin derivatives, bentonite, sugars and water—soluble synthetic high molecular-weight nces such as polyvinyl alcohol, polyvinyl idone and polyacrylic acids. Examples of isers are PAP (acid isopropyl phosphate), BHT (2,6-di-tert—butylmethylphenol), BHA re of 2-tert-butylmethoxyphenol and 3—tert—butylmethoxyphenol), synergists such as piperonyl butoxide, vegetable oils, mineral oils, ?sh oils, surfactants and fatty acids or esters thereof.
Emulsifying agents that may be used are suitably one or more of those selected from non-ionic or anionic fying agents. Examples of non-ionic fying agents include, but are not restricted to, polyoxyethylenealkylphenylether, polyoxyethylenealkylether, polyethyleneglycol fatty ester, sorbitan fatty ester, polyoxyethylene sorbitan fatty ester, yethylenesorbitol fatty ester, polyoxyethylenepolyoxypropylenealkylether. Examples of anionic emulsifying agents include alkyl sulphates, polyoxyethylenealkylether sulphates, sulfosuccinates, taurine derivatives, sarcosine derivatives, phosphoric , alkylbenzenesulfonates and the like. A mixture consisting of polyoxyethylenestyrylphenylether and m allylbenzenesulfonate is preferred. These emulsifying agents may be used in an amount of l to 20 weight parts per 100 weight parts of the compositions of the present 3O invention.
In some embodiments, the compound of formula (I) is formulated as a spray.
The spray may be formulated as a liquid for use in an atomizer or aerosol. In some embodiments, the liquid solubilizes the compound of formula (I), for example, where the liquid or solvent is an oil or hydrocarbon solvent. In other embodiments, the liquid is an s liquid and the formulation is in suspension or emulsion form.
In some embodiments, the composition may include a propellant such as butane, ene, pentane, carbon dioxide or nitrogen.
In some embodiments, the spray may be deployed topically in an environment or on an animal, or may be applied directly to the ant pests. In other embodiments, the compound of formula (I) may be formulated in a viscous formulation that is soaked into a carrier, such as a filter paper or fabric and left at the site of a pest infestation for contact with the pest. In some embodiments, the compound of formula (I) may be formulated in a slow release ation.
The methods of the invention may be deployed as part of an integrated pest ment system where the compound of formula (I) is used in combination with other pesticides, either aneously or sequentially. The compounds of formula (I) are potassium channel tors. In some embodiments, the compound of formula (I) is in combination with another ide which has a different mode of action. In particular embodiments, the pesticide resistant pest is not resistant to the effects of either of the compounds used in combination. In some embodiments, the combination of compound offormula (I) and second pesticide is in a single composition. In other embodiments, the compound of formula (I) and second pesticide are in te compositions. The second pesticide may be chosen from any of those listed in paragraph [0043], i) to xxi) or paragraph [0045] above.
In order that the invention may be readily understood and put into practical effect, particular preferred ments will now be described by way of the following non-limiting examples.
Brief Description of the Figures Figure l is a graphical representation of dose-response curves of a susceptible population ofH. destructor when exposed to ?avesone at concentrations of 3O 0, 3, 10, 30, 100, 300, 1000, 3000 and 10000 mg a.i./L (ppm) at 4, 6, 8 and 24 hours.
Figure 2 is a graphical representation of dose-response curves of susceptible and resistant populations ofH. destructor when exposed to ?avesone at concentrations of 0, 3, 10, 30, 100, 300, 1000, 3000 and 10000 mg a.i./L (ppm) at 24 hours.
Figure 3 is a graphical representation of dose-response curves of susceptible and resistant populations ofH. destructor when exposed to bifenthrin at concentrations of 0, 0.00001, 0.0001, 0.001, 0.01, 0.1, 1.0, 10, 100, 1000 and 10000 mg a.i.fL (ppm) at 24 hours.
Figure 4 is a graphical representation of dose-response curves of susceptible and resistant populations ofH. destructor when d to yrifos at concentrations of 0, 0.7, 7.0, 70 and 700 mg a.i./L (ppm) at 24 hours.
Figure 5 is a graphical representation of dose-response curves of susceptible and resistant populations of green peach aphid d to ?avesone at concentrations of 0, 10, 100, 300, 1000, 2000, 5000, 10000, 30000 and 100000 mg a.i./L and 48 hours exposure. id="p-73" id="p-73" id="p-73" id="p-73"
[0073] Figure 6 is a graphical representation of dose-response curves of susceptible and resistant populations of green peach aphid exposed to ?avesone at concentrations of 0, 10, 100, 300, 1000, 2000, 5000, 10000, 30000 and 100000 mg a.i./L and 96 hours exposure.
Figure 7 is a graphical representation of dose-response curves of susceptible and resistant populations of green peach aphid d to pirimicarb at concentrations of 0.025, 0.25, 2.50, 25.0, 250.0 and 2500.0 mg a.i.lL and 48 hours exposure.
Figure 8 is a graphical representation of dose-response curves of susceptible and resistant populations of green peach aphid d to carb at concentrations of 0.025, 0.25, 2.50, 25.0, 250.0 and 2500.0 mg a.i./L and 96 hours exposure.
Examples Example I: Larval Packet Test — Cattle Tick The larval packet test (LPT) is a modi?cation of that ?rst bed by Stone and Haydock (1962, Bull. Entomol. Res, 563-578, 3O http://dx.doi.org/ 10. 000748530004832X) for evaluation of ?eld resistance in cattle tick (Rhipicephalus microplus) larvae.
The ?rst LPT assay was conducted to identify the potential range of ?avesone idal activity against larvae of a susceptible non-resistant ?eld strain (NRFS) of R. microplus as a reference strain using a wide range of trations (1 in in series).
The test compound, ?avesone, 6—isobutyryl-2,2,4,4-tetramethylcyclohexane- 1,3,5-trione, 96.7%, was used. As its volatility/evaporative properties were unknown, the LPT method was modi?ed to incorporate the use of ly-sized polyethylene plastic sheets to envelop the larval s, minimizing exposure ofthe test active to the atmosphere. id="p-79" id="p-79" id="p-79" id="p-79"
[0079] In on, the use of the solvent trichloroethylene (TCE) was d to avoid the time required for ation in the preparation of test papers. The test solutions were prepared in olive oil only at the diluent and the papers immediately enveloped in the plastic sheets and sealed with bulldog clips to minimize evaporation.
A stock on with a concentration of 100,000 ppm (10%) ?avesone was prepared in olive oil as the diluent (1.035 mL ?avesone (96.7%) to 8.965 mL olive oil) and then further diluted 1 in 10 in series to also give 10,000 ppm, 1,000 ppm, 100 ppm, ppm and 1 ppm concentration. The negative control was olive oil only. No positive control was included in this experiment. Due to the viscosity of the olive oil, all solutions were prepared using e pipetting technique. id="p-81" id="p-81" id="p-81" id="p-81"
[0081] Filter papers (75 mm x 85 mm Whatman® No. 541), with grid patterns, were impregnated on 1/2 of the paper with 225 [LL of each solution using a micro-pipette and immediately folded in half, enveloped in polyethylene plastic and sealed with 3 bulldog clips. The impregnated papers were kept at room temperature on aluminium trays for a minimum of 60 minutes to allow for dispersal across the grid pattern of the paper prior to aliquoting of larvae. The s were prepared in duplicate for each concentration, including the negative control.
An 8 dram vial containing approximately 20,000 hatched 7-21 day old NRFS larvae (about 1 g eggs) was opened and set up on a moated tray with a small amount of detergenated water, about 15 to 30 minute before use. Only larvae that 3O migrated to the top ofthe vial were used in the assay.
Aliquots of approximately 100 larvae were placed into each packet using plastic disposable forceps and the packets rescaled and incubated and 27°C and 85% relative humidity (RH).
After 24 hours, the larval packets were opened and the numbers of dead and live larvae were counted under a magni?cation lamp. Percentage ity was calculated and, where applicable, corrected using Abbott’s Formula (Abbott, 1925, J. ic Entomology, 181256-257): (Treated % mortality) — (control % mortality) —x1 00 100 — (control % mortality) LCso and LC99 values were determined by Probit mortality vs log concentration analysis. Probit values were derived from "Transformation of Percentages to Probit’s Tables" published by Fisher RA. and Yates F. (1938).
The s are shown in Tables 1 and 2.
Table 1: mortality 100,000 LCso and LC99 values were determined and are shown in Table 2.
Table 2 e 2: LPT assay with resistant larvae The LPT Assay of Example 1 was repeated using a narrow range of concentrations, 1 in 2 series, of ?avesone to determine LCso and LC99 values against the susceptible NRFS and the multi—resistant Tiaro nce strain.
The Tiaro strain of R. microplus comprises of about 30% ?uazuron, 60.6% cypermethrin (SP), 57.6% ?umethrin (SP), 16.2% amitraz (amidine), 11.3% DDT, 9.3% chlorpyrifos (OP) and 2.4% dieldrin resistance [2014 acancide ance pro?ling].
The synthetic pyrethroid (SP) cypermethnn was included in the assay as a positive control.
The stock solution of ?avesone (100,000 ppm) was diluted 1 in 10 with olive oil (1 mL to 9 mL diluent) to give 10,000 ppm, which was then further diluted 1 in 2 in series (5 mL to 5 mL diluent) to give 5,000 ppm, 2,500 ppm, 1,250 ppm, 625 ppm, 312.5 ppm and 156.25 ppm concentrations.
For the preparation of the positive l, cypermethrin, a stock solution of a concentration of 10,000 ppm was prepared in 2:1 trichloroethylene (TCE) / olive oil as the solvent (0.0352 g cypermethnn, 94.8% , to 10 mL solvent) and then further diluted 1 in 2 in series (5 mL to 5 mL solvent) to also give 5,000 ppm, 2,500 ppm, 1,250 ppm, 625 ppm, 3125 ppm and 156.25 ppm.
The ?avesone papers were prepared as in Example 1.
The cypermethnn papers were impregnated with 670 [AL of each solution using a micro-pipette and hung on a rack in a fume-hood to allow papers to dry (evaporation of TCE) for a minimum of 60 minutes. The papers were then folded in half and sealed with three bulldog clips, placed on aluminium trays prior to aliquoting the larvae. All packets were prepared in ate.
The negative control papers were ed for both ne (olive oil only) and the positive control, cypermethrin (2:1 TCE/olive oil).
Mortality was assessed at 24 hours and LCso and LC99 values determined by Probit mortality vs log concentration analysis. A dose-response relationship was determined at 24 hours t exposure. The results are shown in Table 3.
Table 3 ,000 5,000 62.22 2.500 2.500 59.72 1,250 1,250 20.90 625 11.76 12.83 625 99.56 21.92 312.5 -_— 312.5 89.01 20.36 —156.25 -_-_ 156.25 67.33 0.56 At 1,250 ppm ?avesone for both strains, some larvae were still waving their legs in the air, however, did not take a step to indicate survival (?accid paralysis). At 2,500 ppm ?avesone for both strains, no movement was noted with 100% mortality observed.
There was no evidence of cross-resistance to ?avesone when comparing LC50 and LC99 data n the NRFS and Tiaro strains.
Negative control mortality ranged from 0% to 0.51% and where applicable was corrected using Abbott’s formula. 1 0 ] LC50 and LC99 values were determined using Probit mortality vs log concentration analysis and are shown in Table 4.
Table 4 NRFS mu 1109 —540 647 1039 3082 >10,000 1 5 Example 3 The experiment of Example 2 was repeated only on the NRFS strain with dilutions of 1 to 2 in series and ethrin as a positive control. The concentrations of ne were 5,000 ppm, 2,500 ppm, 1,250 ppm, 625 ppm and 312.5 ppm. The concentrations of cypermethrin were 1,250 ppm, 652 ppm, 312.5 ppm, 156.25 ppm, 78.125 ppm and 36.0625 ppm.
Mortality was assessed at 24 hours and LC50 and LC99 values determined by probit mortality vs log concentration analysis.
As with Example 2 at 1,250 ppm ?avesone, some larvae were still waving their legs in the air, however did not take a step to indicate survival (?accid paralysis). 2 5 At 2,500 ppm ?avesone, no movement was noted with 100% ity observed.
Negative control mortality ranged n 2% and where applicable was corrected using Abbott’s formula.
The results are shown in Table 5: Table 5 ——"'—125—0’0" " 1,250 100 312.5 99.16 ——39.0625 -_ id="p-106" id="p-106" id="p-106" id="p-106"
[00106] The LCso and LC99 values are shown in Table 6: Table 6 Example 4 1 0 [00107] It was noted in Example 2 and Example 3 that although 100% mortality was recorded at 1,250 ppm ?avesone concentration after 24 hours contact exposure, some larvae at this concentration, for both the NRFS and Tiaro strains, were still waving the legs in the air but unable to take a step to indicate survival (?accid paralysis), therefore moribund. This ment was conducted to con?rm whether to not these larvae died 1 5 within a further 24 hours contact exposure, with mortality ed at 48 hours. trations of 1,250 ppm, 625 ppm and 312.5 ppm ?avesone concentrations prepared for Example 3 were used on the same day of ation.
Duplicate papers were prepared for both the NRFS and Tiaro strains (including negative controls) as described in e 2. 2 0 [00109] Mortality was assessed at 48 hours and LC50 and LC99 values were determined by Probit mortality vs log concentration analysis. The results are shown in Tables 7 and 8.
Negative control mortality ranged between 0.79% and 3.91% and corrections were made by using Abbott’s formula.
Table 7 " ’ 1' 00 66.83 84.13 312.5 Table 8 Example 5: Evaluation of?avesone as a grain protectant A tory established insect population of Rhyzopertha dominica (QRDl440) with a history of resistance to organophosphates and pyrethroids were used in this study.
Residue free organically produced Wheat grain was used in the study. The moisture content of the wheat was kept at 11%.
Test solutions of ?avesone (25 ppm), deltamethrin (K-Obiol®, 1 ppm) and chlorpyrifos (Reldan®, 5 ppm and 10 ppm) in water were prepared. Water was used as the control sample. Five lots of 240 g of wheat was weighed into glass 1 L capacity jars, one jar per treatment and control. id="p-114" id="p-114" id="p-114" id="p-114"
[00114] The test solutions and control solutions were pipetted onto the inside of one of the jars (one jar per sample) immediately above the grain surface at a rate equivalent to 10 mL of solution per kg of wheat. The jars were sealed, brie?y shaken and tumbled by hand, then d mechanically for 10 minutes. The moisture content was 12%, ing the upper limit accepted by Australian bulk handling companies. The day after treatment, each 240 g wheat sample was d into three replicates of 80 g and placed into glass jars 250 mL capacity. 50 adult R. ca QRD1440 (1 to 3 weeks post-emergence) were added to each jar oftreated or control wheat. Each jar was covered with ?lter paper as a lid and stored at 25°C and 55% RH. for 14 days, after which the wheat sample was sieved to retrieve the adult s. Mortality was recorded. All adults, dead and alive, were discarded. The jars of wheat were incubated for a further 6 weeks and the number of progeny recorded. The results are shown in Table 9: Table 9: 14 clay mortality onRD1440 R. dominica A 0/50 Control B 0/50 Flavesone (25 ppm) .3 11/50 14150 Deltamethrin (1 ppm) 0/50 C 1/50 yrifos (5 ppm) g—1/50 =—0—50 At 25 ppm of ?avesone the QDRl 140 R, dominica resistant strain had higher mortality than the control and other pesticides used. The ?avesone treatment also resulted in less Fl progeny being ed.
Example 6: Concentrations of?avesone The experiment of e 5 was repeated with ?avesone at trations of 25 ppm, 50 ppm and 75 ppm. Water was the control.
The results are shown in Table 10: Table 10: 14 day mortality QRD1440 R. dominica at different?avesone concentrations Control Flavesone (25 ppm) II 2150 /50 0/20 F1avesone(50 ppm) "—— Flavesone (75 ppm) "—— e 7: Control ofresistant strain oflesser grain borer QRDI440 R. dominica The experiment of Example 5 was repeated with ?avesone at a tration of 60 ppm. Water was used as the control. id="p-119" id="p-119" id="p-119" id="p-119"
[00119] The results are shown in Table 11.
Table 11: Response stant strain oflesser grain borer (R. dominica, QRD1440) to ?avesone at a rate of60ppm Control .3— A 50/50 one(60 ppm) .3— 1 0 e 8: Comparative studies with a susceptible strain of lesser grain borer QRDM R. dominica.
The experiment of Example 5 was repeated using a laboratory reared susceptible strain QQRD14 of R. dominica and different concentrations of ?avesone to determine ef?cacy. id="p-121" id="p-121" id="p-121" id="p-121"
[00121] The results are shown in Table 12.
Table 12: Response ofsusceptible strain oflesser grain borer (R. dominica, QQRDM) to?avesone at a broad application range.
Control .3— A 0/50 Flavesone (5 ppm) .3— Flavesone (10 ppm) B 8/50 Flavesone (25 ppm) B 50/50 Flavesone (50 ppm) .3 50/50 50/50 A 50150 Flavesone (100 ppm) B 50/50 C 5050 Example 9: Control ofHalotydeus destructor (redleggea' earth mite)- dose response 5n susceptible populations ] The ef?cacy of ?avesone against H. destructor was assessed using the glass vial technique ped by Hof?nann et al. (1997, Exp. Appl. Acarol., 21: 151-162), adapted for plastic Vials. A susceptible population of mites was collected from capeweed (Arctotheca ula) at a Victorian site (37° 40’33"S, 145° 07’ 45"E) that had no known history of insecticide ation. Following collection, samples were stored in small plastic containers with leaf material and paper towel to absorb excess moisture. Containers were kept at 4 °C prior to testing.
Serial dilutions of each insecticide were prepared from the compositions shown in Table 13: Table 1 3 Flavocide 500EW Flavesone 500 g/L 2000 mL/100L 10000 mg a.i./L Talstar® 250EC Bifenthrin 250 g/L 40 mL/100L 100 mg a.i./L LorsbanTM 500EC yrifos 500 g/L 140 mL/100L 700 mg a.i./L The test compositions included 0.1% Tween 20 nic surfactant to aid the spread of insecticides when coating plastic vials. This concentration of Tween 20 has been usly shown to have no toxic effect on H destructor. For each insecticide concentration tested, 3, 10, 30, 100, 300, 1000, 3000 and 10000 mg a.i./L (ppm), imately 10 mL of solution was poured into a 15 mL plastic vial and swirled to ensure a complete coating, with excess liquid d. Eight vials were coated per concentration and were left to dry ovemight. Control vials were treated in the same way but with water used in place of test composition.
Eight susceptible H. destructor mites were then placed into each vial along with a leaf of common vetch (Vicia sativa). The leaf was added to provide food and increase humidity. Vials were then sealed with a lid and placed at 18 °C. After 4, 6, 8 and 24 hours of exposure, the mites were scored as alive g freely), incapacitated (inhibited movement), or dead (no movement over a 5 second period). Incapacitated individuals were pooled with dead individuals for analysis as they invariably died and therefore did not contribute to the next generation.
The results for ?avesone are shown in Figure 1. Mortality ofH. destructor increased dramatically between 100 and 300 mg a.i./L and mortality increased with duration of exposure. At 4 hours of exposure, ?avesone at 300 mg a.i./L had caused an average of 55 % mortality, while at application rates below this, little mortality was observed. All application rates above 300 mg a.i./L resulted in 100 % mortality by 4 hours exposure. By 8 hours of exposure, mortality at 300 mg a.i./L had risen to 100 %.
At lower application rates, increased mortality was observed at 24 hours. e 10: l ofHalotya'eas destructor (Redleggea’ earth mite) - dose response in tible and resistant populations The experiment set out in Example 9 was repeated with susceptible and resistant populations ofH. destructor, with the exception that the mites were observed at 6 and 24 hours. The resistant population ofH destructor was collected from a e paddock in the Upper South-East district of South Australia, where resistance to 3O synthetic pyrethroids was confirmed in late 2016.
The data produced in the assays were assessed for trations that caused 50, 90 and 99 % mortality (lethal concentration, LC), together with 95 % confidence intervals (CIs) and were estimated from observations of mortality after 24 hours exposure using a al logistic regression (Robertson & er, 1992, Pesticide Bioassays with Arthropods. CRC: Boca Raton, Venables & Ripley, 2002, Modem Applied Statistics with S. Springer: New York). Population differences were tested by comparing the change in model deviance with and without the population factor (different regression intercepts for each population). ences in sion slopes between populations were tested by comparing the change in model ce with and without the population x dose interaction term. The resistance ratio of the insecticide- resistant population was estimated as the ratio of its LC50 to that ofthe susceptible population. All analyses were performed using R 3.3. (R Core Team 2017, R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. htt 3:;‘fwwwR- n'o’ector").
Dose response curves showing the effects of ?avesone on tible and resistant H. destructor tions after 24 hours exposure are shown in Figure 2.
Flavesone was equally ive against both insecticide-resistant and susceptible populations as evidenced by closely aligning esponse curves for both populations ()8 = 1.40, df= l, p = 0,24). LC50 values (and 95 % CIs) were calculated as 40.6 (33.3 — 49.6) mg a.i./L and 34.2 (27.9 — 41.9) mg a.i./L for the susceptible and resistant populations, respectively, for ?avesone as shown in Table 14. There was no evidence that the regression slopes for concentration were significantly different between populations ()8 = 0.01, df= 1, p 0.91).
A large difference was seen in sensitivity to bifenthrin between susceptible and resistant populations ()8 = 167.57, df = 1, p = 00001) as shown in Figure 3. ing the LC50 values between populations showed that the resistant population requires about 3,500 times the dose of bifenthrin compared to the tible population to achieve 50 % mortality after 24 hours. This population likely ed a mixture of resistant and susceptible individuals. The LC50 value for the tible population of 0.04 (0.03 — 0.08) mg a.i./L is consistent with previous studies using H. destructor collected from this location. The regression coefficients were also 3O significantly ent between populations ()8 = 28.76, df = l, p = 00001).
For chlorpyrifos, dose-responses were also significantly different between the insecticide-resistant and susceptible populations ()8 = 44.13, df = l, p = , 0.0001).
The ant population was 6.5 times more resistant to chlorpyrifos than the susceptible population. This is comparable to the organophosphate resistance seen in South Australia. There is no evidence that the regression slopes for concentration were different between populations. ()8 = 1.77, df = l, p = 0.18). id="p-132" id="p-132" id="p-132" id="p-132"
[00132] LDso, LD90 and LD99 values and con?dence intervals for 24 hours exposure are shown in Table 14.
Table 14 Flavesone Susceptible 1.75 (0.17) 33.25 — 49.58 105.76 — 192.15 335.01 — 940.61 ant 1.78 (0.17) 27.93 — 41.91 86.60 — 160.47 267.01 — 774.52 Bifenthrin Susceptible 0.54 (0.05) 0.03 — 0.08 1.03 — 6.86 44.58 — 1218.91 Resistant 0.27 (0.05) 59.03 — 350.21 6.8 X 2 x106 1.1 X 108-17 x1012 Chlorpyrifos Susceptible 1.68 (0.26) 0.14 — 0.30 0.44 — 1.33 1.25 — 8.10 Resistant 1.27 (0.18) 0.93 — 2.01 4.15 — 14.50 17.49 — 152.04 These results show that ne is ef?cacious against H. destructor in both susceptible and insecticide-resistant populations and caused 50 % mortality at 24 hours with a concentration between 34 — 40 mg a.i./L.
Example 1]: Efficacy ofFlavesone against susceptible and resistant populations of green peach aphid Colonies ofM persicae (green peach aphid) were established from long- term laboratory cultures of a known insecticide-susceptible population, and a population which has previously been shown to be resistant to ates and synthetic pyrethroids. Each colony was maintained separately on bok choi plants (Brassica napus chinensis) within an exclusion cage in a constant temperature room at 24°C with a photoperiod of 16:8 LD.
Laboratory bioassays were used to determine the ef?cacy of ?avesone againstM persicae following the leaf dip method described in Moores et a1. (1994, ide Biochemistry and Physiology, 49, 114-120). A pilot study was ?rst conducted which con?rmed that the leaf dip method was appropriate to elicit a clear dose response for ide SOOEW againstM persicae, and to determine the appropriate rate range and timing of ity assessments (scored at 24, 48, 72 & 96 hours) (data not shown).
Bioassays were then conducted to assess the ef?cacy of ?avesone against a susceptible and resistant population ofM persicae, and to calculate LC values. The ef?cacy of a conventional icide, pirimicarb, was tested for comparison. Nine concentrations of ?avesone ranging from lxlO'3 to 10 times the proposed ?eld rate (Table 15), and six concentrations of carb were ly d and tested, along with a water control, against the susceptible and resistant aphid populations. Leaf discs (25 mm diameter) cut from bok choi leaves were submerged for 1 second in the insecticide solutions, or in the water l, and placed adaxial side up on 10 g/L agar in 35 mm petri dishes. Six ate leaf discs were prepared per treatment. Once leaves were air-dry, eightM persicae nymphs were transferred to each insecticide-dipped leaf disc using a ?ne-haired paintbrush. 3O [00137] After aphid introduction, each petri dish was inverted onto a lid containing a mm diameter ?lter paper to control humidity. All petri dishes were then placed into an incubator held at 18°C i 2°C with a photoperiod of 16:8 LD cycle. At 48 & 96 hours, aphids were scored as alive (vibrant and moving freely), dead (not moving over a second period), or incapacitated (inhibited movement). Incapacitated individuals were pooled with dead duals for analysis as they invariably die and therefore do not contribute to the next generation.
Table 15. Chemical ents used in this study.
Flavocrde 500EW Flavesone 500 g/L 2000 mL/100 L* 10,000 mg a.1./L Pirimor 500WG Pirimicarb 500 g/kg 500 g/ha 2,500 mg a.i./L *Suggested ?eld rate of ?avesone 500EW provided by the client (1% ?avesone v/v). 1 0 Data analysis ] Dose-response curves were generated by plotting percentage ity against log concentration. Mortality data was analysed using a logistic regression model with random effects. Logistic regression is suited for the analysis of binary response data (i.e. dead/alive) with the random effect ent ofthe model controlling for the non-independence of mortality scores within replicates. Concentrations that resulted in 50, 90, and 99% mortality l concentration, LC) (along with 95% confidence intervals, CIs) were calculated using a binomial logistic regression (Robertson & Preisler 1992, Pesticide Bioassays with Arthropods, CRC: Boca Ratan, Venables & Ripley 2002, Modern Applied Statistics with S, Springer, New York, 2 O http://www.stats.ox.ac.uk/pub/MAS S4). Population differences were tested by comparing the change in model deviance with and without the population factor (different regression intercepts for each tion). Differences in regression slopes between populations were tested by comparing the change in model ce with and without the population X dose interaction term. 2 5 [00139] Analyses were conducted using R version 3.3.1 (R Development Core Team 2017. R: A language and environment for statistical computing. R tion for Statistical Computing, Vienna, Austria, http://R-projectorg).
Results While the dose—response curves for the susceptible and ant populations 3 O exposed to ?avesone appeared similar at 48 hours (Figure 5), a significant difference between populations was detected (c2 = 8.09, df = l, p <0.01). However, by 96 hours, the dose-response curves for the susceptible and resistantM persicae populations exposed to ?avesone had become more closely aligned and were not signi?cantly different (c2 = 0.78, df= l,p = 0.38) (Figure 6). LC50 values (and 95% CIs) after 96 hours exposure were estimated as 2,731 (2,259 - 3,303) mg a.i./L for the susceptible population, and 3,151 (2,568 - 3,865) mg a.i./L for the ant population (Table 16).
The regression slopes between populations did not differ significantly at 48 hours (c2 = 0.49, df= 1,p : 0.48) or 96 hours (c2 = 0.72, df= l,p : 0.40). 1 0 Table 16. LD50, LC90, ana’ LC99 values (and 95% nce intervals) and sion coe?icientsforM persicae, computedfrom logir modelsfor ses to insecticides after 96 hours exposure.
Flavesone Susceptible (2,259 - 3,303) 6,034 (4,488 - 8,113) 14,330 (8,826 - ) Resistant 3,151 (2,568-3,865) 7,929 (5,700 - 11,028) 21,708 (12,551 - 37,544) Pirimicarb Susceptible (13.4 — 25.6) 78.9 (47.2 - 132) 384 (154.9 — 952.2) Resistant At 48 and 96 hours, there were clear differences in the esponse curves between the susceptible and resistant populations after exposure to pirimicarb (48hr: c2 = 269.9, df= 1,1) <0.0001, 96 hr: c2 = 257.5, df= l,p <0.0001) (Figures 7 & 8). The regression slopes were also signi?cantly different between populations (48hr: c2 = 66.6, df= 1, p <0.0001, 96 hr: c2 = 107.2, df= l,p <0.0001). The estimated LC50 for the susceptible population after 96 hours of 18.5 mg a.i./L is tent with previous laboratory studies usingM. persicae (Umina et al. 2014, Journal of Economic Entomology, 107(4), 1626 163 8). Very low mortality observed for the resistant population when exposed to pirimicarb prevented the calculation of meaningful LC values (Table 16).
This study demonstrates that ?avesone is ef?cacious tM. ae.
The LC50 of ?avesone after 96 hours re was between 2,731 - 3,151 mg a.i./L.
The y of pirimicarb was very high against the susceptible population and matched closely with previously published bioassay data. Resistance to pirimicarb in the insecticide-resistant population was ed. This population is also resistant to synthetic pyrethroids, as demonstrated by pesticide bioassay results and genetic screening (see Umina et al. 2014) id="p-143" id="p-143" id="p-143" id="p-143"
[00143] The dose-response curves for ?avesone for the susceptible and resistant tions were y aligned at 96 hours after exposure. This shows that ?avesone is effective againstM. persicae populations with resistance to ates, and that ?avesone has a different mode of action to this class of insecticide. There was some evidence for population differences in responses after 48 hours. The reason(s) for this remains unclear but could re?ect natural differences between the populations such as colony health, general hardiness, or bacterial endosyrnbionts.
Example 12: Toxicity of?avesone to Aedes aegypti LVP (insecticide susceptible and PRS insecticide resistant s L3 . id="p-144" id="p-144" id="p-144" id="p-144"
[00144] Mosquito larval topical assay techniques were conducted.
A dose response assay was used to determine the lethal concentration (LC50) value, performed with a minimum 5-point dose of ?avesone diluted in sterile ddeO, minimum of 4 technical replicates (5 mosquitos per replicate) per dose.
Two species ofmosquito were used. Aedes aegypti (yellow fever mosquito) 3O Liverpool strain (insecticide tible, LVP) and PRS Puerto Rican strain (synthetic pyrethroid resistant) at L3 stage larvae.
Negative control: vehicle ve l: technical grade synthetic pyrethroid (SP) and organophosphate (OP): deltamethrin (SP), permethrin (SP), and malathion (OP).
Phenotypic endpoint: scored for death/paralysis at 24, 48 and 72 hours.
Dose points (selectedfrom pilot assays which are not : Flavesone: 6.25ug/mL, 25.0ug/mL, L, 75ug/mL & lOOug/mL, H20 control Deltamethrin: 1.56ng/mL, 6.25ng/mL, /mL, 25ng/mL, 50ng/mL, 0.625% DMSO negative control Permethrin: /mL, 12.5ng/mL, 25ng/mL, 50ng/mL, lOOng/mL, 0.625% DMSO negative control Malathion: 0.0156ug/mL, 0.0625ug/mL, 0.125ug/mL, 0.25ug/mL, lug/mL; 0.5% EtOH negative control ] Larvae were transferred to a 24 well tissue plate using a wide-bore plastic transfer pipette, 5 larvae per well. The water was gently removed from the well with a 1 mL pipette and an equivalent amount ofddeO was added. The appropriate volume 1 5 of test compound was added to each ofthe four replicate wells per treatment and the plate gently swirled to ensure uniform mixing. The plate was placed in a test or growth chamber under constant conditions of 22-25 0C and about 75-85% relative humidity on a 12 h light/12 hr dark cycle. Assessment of dead and non-responsive larvae was undertaken at 24, 48 and 72 hours. 2 0 [00148] The results are shown in Table 17.
Table 1 7 iioéu?'g'th' 40.5 ug/mL 4.9 ng/mL 16.2 ng/mL 38.9 ng/mL 39.7 ug/mL 3.7 ng/mL 16.6 ng/mL 29.75 ng/mL < 2> w 48 hours 40.5 ug/mL 50.1 ng/mL (N=2) 150.5 ng/mL 176.7 ng/mL 39.7 ug/mL 412 ng/mL (N=2) 128.0 ng/mL 126.7 ng/mL Example 12: tion ofFlavesone as a grain protectant against major stored grain pests having resistance to commonly sticides Insects id="p-149" id="p-149" id="p-149" id="p-149"
[00149] tory established s (both susceptible and resistant) of five species were considered for this stage of experiments. The resistant strains listed below represent the grain protectant—resistant genotypes that are commonly encountered in grain storages in Australia, particularly in the eastern grain belt: 1 0 o R. dominica strain QRD1440 is resistant to OP protectants and pyrethroids. o T. eum strain QTC279 is resistant to malathion and bioresmethrin o C. ineus strain QCF73 is resistant to phosphine o O. surinamensis strain QOS3 02 is resistant to fenitrothion & chlorpyrifos-methyl o S. oryzae strain QSO3 93 is resistant to fenitrothion Testing Program Grain treatment and bioassays Residue and insect-free organically produced wheat was used in this study.
Moisture content of the wheat before treatment was kept at 11%. Chemicals for use in these 2 0 experiments: flavesone, K-Obiol EC Combi (50 g/L Deltamethrin, 400 g/L PEG) and Reldan (500 g/L Chlorpyrifos-methyl) were obtained from ne logy, Bayer Crop Science, and Dow AgroSciences respectively. Two rates (25 and 60 ppm) were considered for the stand alone ?avesone experiments.
For each strain of the borers (internal feeders), R. dominica and S. , three lots 2 5 of 160 g of wheat was weighed into glass jars (500 mL capacity), i.e. one jar per treatment and another for the control (distilled water only). The solutions of each treatment (prepared at the predetermined dilution rates as alone and in combinations) were ed separately onto the inside of glass jars immediately above the grain e at the rate equivalent to 10 mL of solution per kilogram of wheat. Distilled water was applied to control grain at the same rate as 3 O the treatment. All jars were sealed, brie?y shaken and tumbled by hand, and then tumbled mechanically for 1 hour. Moisture content after treatment was 12%, re?ecting the upper limit ed by Australian bulk handling companies. One day after treatment, each 240 g lot of wheat was divided into three replicates of 80 g, which were placed into separate glass jars (250 mL capacity). The procedure for T. castaneum, C. ferrugineus and 0. surinamensis was kept the same except that three lots of 600 g of wheat was treated per strain. One day after treatment each 600 g lot of wheat was divided into three replicates of 190 g which was then placed into glass jars (500 mL capacity). The remaining 30 g of wheat was grounded to ?our, divided into three lots of 10 g and added to the relevant replicates of whole wheat so that each replicate weighed a total of 200 g. The aim of grinding 5% of each replicate to ?our was to improve the reproduction of these three pest species, which are external feeders. The above activity was repeated twice over the following two days for making a total of three replicates for each treatment. id="p-152" id="p-152" id="p-152" id="p-152"
[00152] Bioassays were initiated by adding 50 adults (1-3 weeks post-emergence) to each jar of treated or control wheat. Each jar was covered with a filter paper lid and stored in a constant environment room at 25°C and 55% r.h. for 2 weeks, after which the adults were sieved from the wheat and mortality recorded. Thereafter, all adults (dead and alive) were ded and the jars of wheat were incubated for a further 6 weeks when the number of adult progeny were recorded. To synchronise progeny emergence, jars containing S. oryzae and O. surinamensis were ted at 25°C and 55% r.h., and jars containing the other species were incubated at 30°C and 55% r.h..
Data analysis Each data set is presented in simple tables with percentage adult mortality and number of live adult F1 progeny (mean :: standard error of 3 replicates) of each species as well the percentage progeny reduction calculated from the mean s of F1 progeny in the d wheat and ted control.
Results Effectiveness ofFIavesone id="p-154" id="p-154" id="p-154" id="p-154"
[00154] Control mortality in both susceptible and resistant strains of all 5 species was negligible (0-1.3%) (Tables . The number of adult progeny produced in controls of R. dominica were 234 and 211 for the tible (QRD 14) and resistant strain (QRD1440), respectively (Table 18); 118 (QTC4) and 321 (QTC279) for T. castaneum (Table 19), 360 (QCF31) and 344 (QCF73) for C. ineus (Table 20), 348 ) and 412 (QOS302) for 3O O. surinamensz‘s (Table 21) and 716 (LS2) and 610 (QSO393) for the susceptible and resistant strains, tively, of S. oryzae (Table 22).
As expected, 25 ppm of ne failed to achieve complete mortality of adults in both the susceptible (QRDl4) and resistant (QRD1440) strains of R. dominica, but achieved 100 and 88% progeny reduction in the respective s (Table 18). However, the higher rate of 60 ppm of ?ayesone achieved complete control of adults and progeny of both strains (Table 1) validating the Phase I results.
Against the strains of other four species, however, both the proposed rates (25 and 60 ppm) of ?ayesone failed to achieve complete mortality of adults (Tables 19-22); although complete progeny reduction was achieved at 60 ppm in C. ferrugineus and 0. surinamensz‘s (Tables 20 and 22). Both rates of ?avesone under performed against the susceptible (QTC4) and resistant (QTC279) strains of T. castaneum with no adult mortality achieved and a maximum of 45% progeny reduction yielded against the former and a 36% against the latter at the higher rate of 60 ppm (Table 19). t C. ferrugineus, adult mortality reached 90 and 62% in the susceptible (QCF31) and resistant (QCF73) strains, respectively, at the highest dose of 60 ppm (Table 20). At the lower dose of 25 ppm, progeny reduction in this species was recorded at the similar level of 75% for both strains and a 100% y reduction was recorded at the 60 ppm level (Table 20). In the case of O. surinamensz‘s, ?avesone at 25 ppm achieved adult mortalities of 22 and 0.7% in the susceptible (VOS48) and resistant (QOS302) strains, respectively; and a maximum of 91% in the former and 14% in the latter at the higher dose of 60 ppm (Table 21), Both rates of ?ayesone, however, produced very high percentage of progeny reduction (61-99%) at 25 ppm and te reduction of progeny (100%) at 60 ppm in both strains of this species (Table 21). The iveness of ?ayesone against S. oryzae was similar to that observed against T. eum (Table 18 and 22). Both rates failed to achieve any icant mortality against the adults of both s (Table 22). At 60 ppm, however, ?avesone achieved 29 and 50% progeny reduction, in the resistant (QSO393) and susceptible (LS2) strains, respectively (Table 22).
Table I 8: E?eetiveness ofFlavesone against adults geny production othyzopertha dominica in treated wheat. l , Flavesone 25 98.0 :: 1.2 0.0 :: 0.0 100 one 60 100 :: 0.0 0.0 :: 0.0 100 QRD1440 Control 0.0 :: 0.0 211.0 :: 69.4 - Flavesone 25 56.7 :: 4.1 23.7 :: 9.0 88.8 Flavesone 60 *Mean i standard error Table 19. E?’ectiveness ofFlavesone against adults andprogeny production ofTribolium castaneum in treated wheat.
Control Flavesone 25 0.0 :: 0.0 120.0 :: 16.1 - Flavesone 60 0.0 d: 0.0 65.0 d: 3.2 45.2 QTC279 l 0.7 2 07 321.3 2 35.0 - Flavesone 25 0.0 :: 0.0 265.3 :: 27.7 17.4 Flavesone 60 *Mean in standard error Table 20. E?ectiveness esone against adults andprogeny production ofCryptolestesferrugineus in treated wheat. l . . .
Flavesone 25 27.5 :: 17.5 72.0 :: 20.3 76.5 Flavesone 60 90.0 d: 2.0 0.0 d: 0.0 100 344'3 :1: QCF73 Control 0.0 d: 0.0 - Flavesone 25 3.3 d: 1.3 83.7 :t 6.5 75.7 Flavesone 60 62.0 :: 6.1 0.0 :: 0.0 100 *Mean i standard error Table 21. E?ectiveness ofFlavesone against adults andprogeny production ofOryzaephilus l O surinamensis in treated wheat. 348.3 :I: 32.3 Flavesone 25 22.7 :: 2.4 1.3 :: 0.7 99.6 Flavesone 60 91.3 i 5.9 0.0 2 0.0 100 QOS302 Control 0.0 :: 0.0 412.3 :: 10.1 - Flavesone 25 0.7 d: 0.7 160.3 d: 15.7 61.2 Flavesone 60 14.7 :: 8.7 0.0 :: 0.0 100 *Mean in standard error _ 50 _ Table 22. iveness ofFlavesone against adults andprogeny production ofSitophilus oryzae in treated wheat.
L82 Control 0.0 :: 0.0 716.0 :: 75.8 - Flavesone 25 1.3 :: 0.7 735.3 :: 60.6 - one 60 4.0 :: 1.2 355.3 :: 64.7 50.3 QSO393 Control 0.0 :I: 0.0 610.0 :I: 81.5 - 572.7 :1: Flavesone 25 0.7 :: 0.7 6.1 100.9 Flavesone 60 0.7 :: 0.7 430.0 :1: 51.0 29.5 *Mean :: standard error Example 13: Evaluation ofcombination of?avesone and chlorpyrifos—methyl (Reldan) against major stored grain pests having resistance to commonly used pesticides.
The experiments of e 12 were repeated using a combination of ?avesone and chlorpyrifos-methyl. id="p-158" id="p-158" id="p-158" id="p-158"
[00158] Across all the combined treatment experiments, control mortality in both susceptible and resistant strains of all 5 species was negligible (0-3%) (Tables 23 -27).
The number of adult progeny produced in R. dominica controls were 186 for the susceptible (QRD14) and ant (QRD 1440) strains (Table 23), 59 (QTC4) and 480 (QTC279) for T. castaneum (Table 24), 467 (QCF31) and 188 (QCF73) for C. ferrugineas (Table 25), 526 (VOS48) and 429 (QOS302) for O. surinamensis (Table 26) and 720 (LS2) and 565 (QSO393) for the susceptible and ant strains, respectively, of S. oryzae (Table 27).
All experimental combinations of ?avesone and chlorpyrifos-methyl applied both at the higher and lower rates were highly successful against the susceptible strains of all 5 test species, with of 100% adult mortality and progeny ion (Tables 23- 27). The effectiveness of all these combinations was st against the resistant strain of C. ineus, where complete control of adults and progeny were achieved (Table 26). Moreover, with the exceptions of 99% progeny reduction in a couple of combinations, all these treatments achieved 100% l of progeny in resistant strains of T. castaneum (QTC279), 0. surz'namensis (QOS302) and S. oryzoe (QSO393) (Tables 24, 26 and 27). Against the resistant strain of R. dominica 40), r, complete adult mortality was achieved only at the combination of ?avesone 60 + chlorpyrifos-methyl 5 and complete y reduction was achieved in grain treated with the ations of ?avesone 30 + chlorpyrifos-methyl 10, ?avesone 60 + chlorpyrifos-methyl 5, ?avesone 60 + chlorpyrifos—methyl 10 (Table 23).
Table 23. E?ectiveness ofFlavesone in combination ofChlorpyrifos-methyl (0P) against adults and o e oth 20 e tha do i icai t eated heat 186.7 :I: QRD14 Control 0.0 i 0.0 _ Flavesone 30 + chlorpynfos- 100 i 0.0 0.0 i 0.0 100 methyl 5 Flavesone 30 + chlorpynfos- 100 i 0.0 0.0 2: 0.0 100 methyl 10 Flavesone 60 + chlorpynfos- 100 i 0.0 0.0 i 0.0 100 methyl 5 Flavesone 60 + chlorpynfos- 100 :1: 040 0.0 i 0.0 100 methyl 10 1867 i QRD1440 Control 0.7 :t 0.7 - Flavesone 30 + chlorpynfos- 81.3 i 7.7 4.3 i 3.0 97.7 methyl 5 Flavesone 30 + chlorpynfos- 96.0 i 0.0 0.0 2: 0.0 100 methyl 10 one 60 ‘ + chlorpynfos— 100 i 0.0 0.0 i 0.0 100 methyl 5 Flavesone 60 + chlorpynfos- 99.3 i 0.7 0.0 i 0.0 100 methyl 10 *Mean :: rd error Table 24. E?ectiveness ofFlavesone in combination ofCblorpyrifos—methyl (OP) against adults and progeny ofTribolium castaneum in treated wheat.
QTC4 Control 2.0 i 0.0 59.3 26,1 - 2:35p? 30 + chlorpyrifos- 100 i 0.0 0.0 :: 0.0 100 Flavesone 30 + chlorpynfos- 100 i 0.0 0.0 :i: 0.0 100 methyl 10 _ 52 _ Flavesone 60 + chlorpyrlfos- 100 i 0.0 0.0 i 0.0 100 methyl 5 Flavesone 60 + chlorpyr1fos- 100 i 0.0 0.0 :: 0.0 100 methyl 10 4807 :l: QTC279 Control 0.0 i 0.0 _ Flavesone 30 + chlorpyrIfos- 99.3 i 0.7 0.0 :: 0.0 100 methyl 5 Flavesone 30 + chlorpyrlfos- 100 i 0.0 0.0 :: 0.0 100 methyl 10 one 60 + chlorpyr1fos- 100 i 0‘0 0.0 i 0.0 100 methyl 5 Flavesone 60 ' + chlorpyr1fos_ 100 i 0.0 0.0 :: 0.0 100 methyl 10 *Mean in standard error Table 25. veness ofFlavesone in ation okalorpyrifOS-methyl (0P) against adults and fC ' ' t l t f t t d h t Control Flavesone 30 + chlorpyrifos- methyl 5 Flavesone 30 -- chlorpyrifos- methyl 10 Flavesone 60 -- chlorpyrifos- methyl 5 Flavesone 60 + chlorpyrifos- methyl 10 Control Flavesone 30 + chlorpyrifos- methy15 Flavesone 30 + chlorpyrifos- methyl 10 Flavesone 60 + chlorpyrifos- methy15 Flavesone 60 + yrifos- methyl 10 *Mean in standard error Table 26. E?ectiveness ofFlavesone in combination rpyrifos-methyl (0P) against adults and progeny ofOryzaephilus surinamensis in treated wheat.
QVOS48 Control Flavesone 30 + chlorpyrifos- methyl 5 Flavesone 30 + chlorpyrifos- methyl 10 one 60 + yrifos- methyl 5 one 60 + chlorpyrifos- methyl 10 QOS302 Control Flavesone 30 + chlorpyrifos- methyl 5 one 30 + chlorpyrifos- methyl 10 Flavesone 60 + chlorpyrifos- methyl 5 Flavesone 60 + chlorpyrifos- methyl 10 *Mean i stande error Table 27. E?ectiveness ofFlavesone in combination ofChlorpyrifos—methyl (OP) against adults and progeny ofSitophilus oryzae in treated wheat.
Control 2.7 i: 2.7 720.3 ?: 112.3 Flavesone 30 + chlorpyrifos- 100 d: 0.0 100 d: 0.0 methyl 5 Flavesone 30 + chlorpyrifos- 100 :l: 0.0 100 :l: 0.0 methyl 10 Flavesone 60 + chlorpyrifos- 100 i 0.0 100 i 0.0 methyl 5 Flavesone 60 + chlorpyrifos- 100 d: 0.0 100 d: 0.0 methyl 10 QSO393 Control 0.0 i: 0.0 565.7?: 35.0 Flavesone 30 -- chlorpyrifos- 100 i: 0.0 0.3 i: 0.3 99.9 methyl 5 Flavesone 30 -- chlorpyrifos- 100 :: 0.0 00¢ 0.0 100 _ 54 _ methyl 10 Flavesone 60 + chlorpynfos- 100 2: 0.0 0.7 i 1.3 99.9 methyl 5 Flavesone 60 + chlorpyrifos- 100 i 0.0 0.0 i 0.0 100 methyl 10 *Mean in rd error Table 28 es an overview of the effectiveness of the combination of chlorpyrifos-methyl and ?avesone.
Table 28. Overview ofe?ectiveness ofFlavesone in combination with Chlorpyrifos-methyl (CM) at d ' ' ‘ d ’ R. domznzca uscepti e Resistant T. eum Susceptible Resistant Cl ferrugineus Susceptible 0. surinamensis Susceptible IMIIIIMIIIIMIII - eeeee Seeeeeeee "Sim -m---nm- Example 14: Evaluation ofthe combination of?avesone and deltamethrin (K-Obiol) against R. ca susceptible and resistant strains.
] The Experiment of Example 12 was repeated using a combination of ?avesone and deltamethrin with R. dominica susceptible QRD14 and resistant QRD 1440 strains. id="p-162" id="p-162" id="p-162" id="p-162"
[00162] In these ments, the control ity remained below 1% in both the susceptible and resistant strains of this species and similar number of live adult progeny (126 and 125) were emerged (Table 29). In all combinations, complete control of both adults and progeny was achieved against the susceptible strain (QRD14), and a high level of control was achieved against the resistant strain (QRD1440) (Table 29).
Against adults ofthe resistant strain, all combinations yielded percentage mortality of %. Similarly, all combinations yielded 99-100% reduction of progeny of the resistant strain QRD1440 (Table 29).
The s are shown in Table 29.
Table 29‘ E?ectiveness ofFlavesone in combination ofDeltamethrin against adults andprogeny of Rhyzopertha a’ominica in treated wheat. 126.3 in QRD14 Control 0.7 :: 0.7 ' 31?0 5+ 100 0'0 0'0 0'0 100 5231332331313? 100"") 0‘0"") 100 533532131116st 100"" 00:0" 100 533323316131+ 1000") 00:0" 100 125 0 i QRD1440 Control 0.7 0.7 ‘ gill/3:312:30: 93‘3 3‘5 1'0 1’0 99.2 533531233131? 1+ 97-3 *0‘7 0‘0"") 10° giltvaiigltlfrfx?0 5+ 100 0'0 0'0 0'0 100 Flavesone 60 + 99.3 2: 0.7 0.0 :: 0.0 100 deltamethrin 1 *Mean i standard error

Claims (18)

The claims defining the invention are as follows:
1. A method of controlling pesticide resistant pests, wherein the pesticide resistant pests are insect pests ing an ltural environment, said method comprising 5 applying to the agricultural environment a compound of formula (I) wherein R1 is selected from –C(=O)R7, -OR8, -SR8, -C1-10hydroxyalkyl, -NR9R10, - C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7 and –OSO3R8; R2 is selected from hydrogen, -C1-10alkyl, -C2-10alkenyl, aryl and heteroaryl; 10 R3, R4, R5 and R6 are each independently ed from hydrogen, -C1-10alkyl, -C3- 6cycloalkyl, -C2-10alkenyl, -C1-10haloalkyl, dihaloalkyl, -C1- 10trihaloalkyl, -OR8, -SR8, -NR9R10, -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C1- laryl and –C(=O)R7; R7 is selected from hydrogen, -C1-10alkyl, -C2-10alkylaryl, C3-6cycloalkyl, -C2- 15 10alkenyl, -C1-10alkylheteroaryl, -C1-10haloalkyl, dihaloalkyl, -C1- 10trihaloalkyl, -C1-10haloalkoxy, -C1-10hydroxyalkyl, -C1-10thioalkyl, -C1- 10nitroalkyl, -C1-3alkylOC1-3alkyl, -C1-3alkylOC1-3haloalkyl, -C1-3alkylOC1- 3dihaloalkyl, -C1-3alkylOC1-3trihaloalkyl, -OR8, -SR8 and –NR9R10; R8 is selected from hydrogen, -C1-10alkyl, -C2-10alkylaryl, -C3-6cycloalkyl, -C2- 20 10alkenyl, -C1-10alkylheteroaryl, -C1-10haloalkyl, -C1-10dihaloalkyl, -C1- aloalkyl, -C1-10haloalkoxy, -C1-10hydroxyalkyl, -C1-10thioalkyl and -C1-10nitroalkyl; R9 and R10 are independently selected from hydrogen, -C1-10alkyl, -C2-10alkylaryl, -C3- 6cycloalkyl, -C2-10alkenyl, -C1-10alkylheteroaryl, -C1-10haloalkyl, -C1-10dihaloalkyl, -C1- 10trihaloalkyl; or a tautomer thereof; wherein the ltural environment is a plant 25 selected from a crop or tree, the soil and area around the plant as it grows or an area where plants or parts of plants are stored.
2. The method according to claim 1 wherein the compound of a (I) is a nd of formula (II): 17958419_1 (GHMatters) P106256.NZ wherein R11 is selected from –CR12R13R14 or –NR15R16; one of R12 and R13 is hydrogen and the other is hydroxyl or –OCR17R18R19 or R12 and R13 together form an oxo group (=O) or a =N-OH group; 5 R14 is –CH(CH3)CR20R21R22, (CH3)CR20R21R22 or –CH(CH3)CH2CR20R21R22; R15 and R16 are ndently selected from hydrogen and C1-10alkyl; R17, R18 and R19 are independently selected from hydrogen or halo; and R20, R21 and R22 are independently selected from hydrogen, hydroxyl, halo, NO2 and – OCR17R18R19; or a tautomer thereof.
3. The method according to claim 1 wherein the compound of formula (I) is a compound of formula (III): wherein one of R23 and R24 is hydrogen and the other is hydroxyl or –OCR27R28R29 or 15 R23 and R24 together form an oxo group (=O); R25 is –CR30R31R32, -CH2CR30R31R32 or 3)CR30R31R32; R26 is H or –CH3; wherein where R26 is H, R25 is –CH(CH3)CR30R31R32; R27, R28 and R29 are independently selected from en or halo; and R30, R31 and R32 are independently selected from hydrogen, hydroxyl, halo, NO2 and – 20 OCR27R28R29; or a tautomer thereof.
4. The method according to claim 1 wherein the nd of formula (I) is selected from: 17958419_1 (GHMatters) P106256.NZ 19_1 (GHMatters) P106256.NZ 19_1 (GHMatters) P106256.NZ or a tautomer thereof.
5. The method ing to any one of claims 1 to 4 wherein the compound of 5 formula (I) is selected from flavesone, permone and isoleptospermone.
6. The method according to claim 5 wherein the compound of formula (I) is flavesone. 10
7. The method according to any one of claims 1 to 6 n the pesticide resistant pests are insects resistant to one or more insecticides.
8. The method according to any one of claims 1 to 7 n the pesticide resistant pest is exposed to the compounds of formula (I) in an amount in the range of about 200 15 ppm to about 800 ppm or about 800 ppm to about 2,500 ppm.
9. The method according to claim 8 wherein the amount of compound of formula (I) is in the range of about 300 ppm to about 600 ppm. 20
10. The method according to claim 8 wherein the amount of compound of formula (I) is in the range of 900 ppm to 2000 ppm.
11. The method according to claim 7 wherein the insect is selected from Rhyzopertha dominica, Sitophilus oryzae, Triobolium castaneum, Oryzaephilus 25 surinamensis or lestes ferrugineus.
12. The method according to any one of claims 1 to 11 wherein the insect is an adult. 17958419_1 (GHMatters) P106256.NZ
13. The method according to any one of claims 1 to 12 wherein the compound of formula (I) is used as part of an integrated pest management system.
14. The method according to any one of claims 1 to 13 wherein a pesticide resistant 5 pest is d to a nd of formula (I) in combination with a second pesticide wherein the second pesticide has a different mode of action from the compound of a (I).
15. The method according to claim 14 wherein the second pesticide is selected from 10 at least one of a sodium channel modulator, an acetylcholinesterase (AChE) inhibitor, a GABA-gated chloride channel antagonist, a nicotinergic acetylcholine or agonist, an allosteric acetylcholine receptor modulator, a de channel actuator, a juvenile e mimic, a homopteran feeding r, a mitochondrial ATP synthase tor, an uncoupler of oxidative phosphorylation, a nicotinic acetylcholine receptor 15 channel blocker, an inhibitor of chitin biosynthesis, a moulting disruptor, an ecdysone receptor agonist or disruptor, an octapamine or agonist, a mitochondrial complex I electron transport tor, an acetyl CoA carboxylase inhibitor, a voltage-dependent sodium channel blocker, a mitochondrial complex IV electron inhibitor, a mitochondrial complex IV electron transport inhibitor or a ryanodine receptor modulator.
16. A method of protecting stored plant parts from pest infestation by pesticide resistant pests comprising ting the plant part with a compound of formula (I) wherein R1 is selected from –C(=O)R7, -OR8, -SR8, -C1-10hydroxyalkyl, -NR9R10, - 25 C(=N-R9)R7, -C(=N-OH)R7, -NO, -NO2, -N(OR8)R7 and –OSO3R8; R2 is selected from hydrogen, -C1-10alkyl, -C2-10alkenyl, aryl and heteroaryl; R3, R4, R5 and R6 are each independently selected from hydrogen, -C1-10alkyl, -C3- alkyl, -C2-10alkenyl, -C1-10haloalkyl, -C1-10dihaloalkyl, -C1- 17958419_1 (GHMatters) P106256.NZ 10trihaloalkyl, -OR8, -SR8, 0, -C(=N-R9)R7, -NO, -NO2, -NR9OR8, -OSO3R8, -C1- 10alkylaryl and –C(=O)R7; R7 is selected from hydrogen, -C1-10alkyl, -C2-10alkylaryl, C3-6cycloalkyl, -C2- 10alkenyl, -C1-10alkylheteroaryl, -C1-10haloalkyl, -C1-10dihaloalkyl, -C1- 5 10trihaloalkyl, -C1-10haloalkoxy, hydroxyalkyl, -C1-10thioalkyl, -C1- 10nitroalkyl, -C1-3alkylOC1-3alkyl, -C1-3alkylOC1-3haloalkyl, -C1-3alkylOC1- 3dihaloalkyl, lkylOC1-3trihaloalkyl, -OR8, -SR8 and –NR9R10; R8 is selected from hydrogen, -C1-10alkyl, -C2-10alkylaryl, -C3-6cycloalkyl, -C2- 10alkenyl, -C1-10alkylheteroaryl, -C1-10haloalkyl, -C1-10dihaloalkyl, -C1- 10 10trihaloalkyl, -C1-10haloalkoxy, -C1-10hydroxyalkyl, -C1-10thioalkyl and -C1-10nitroalkyl; R9 and R10 are ndently selected from hydrogen, -C1-10alkyl, alkylaryl, -C3- 6cycloalkyl, -C2-10alkenyl, -C1-10alkylheteroaryl, -C1-10haloalkyl, dihaloalkyl, -C1- aloalkyl; or a tautomer thereof; wherein the pest infestation is caused by a population of pests comprising the pesticide 15 resistant pests.
17. The method according to claim 16 wherein the plant part is grain.
18. The method according to claim 16 or claim 17 where the pest population 20 comprising pesticide ance pests is selected from Rhyzopertha dominica, Sitophilus oryzae, Triobolium castaneum, Oryzaephilus surinamensis or Cryptolestes ferrugineus. 17958419_1 (GHMatters) P106256.NZ g + 4 h g + 6 h E -“ 8 h gs: + 24 h 3 10 30 00 300 1000 3000 mm Fiovesone tration (mg (LL/1)
NZ760403A 2018-07-06 Control of resistant pests NZ760403B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AU2017902671A AU2017902671A0 (en) 2017-07-07 Control of Resistant Pests
AU2017904935A AU2017904935A0 (en) 2017-12-07 Control of Resistant Pests
PCT/AU2018/050704 WO2019006516A1 (en) 2017-07-07 2018-07-06 Control of resistant pests

Publications (2)

Publication Number Publication Date
NZ760403A NZ760403A (en) 2023-09-29
NZ760403B2 true NZ760403B2 (en) 2024-01-04

Family

ID=

Similar Documents

Publication Publication Date Title
CN112778271A (en) Molecules having pesticidal utility and compositions and methods related thereto
US9474270B2 (en) Methods and compositions for controlling pests
US20230292751A1 (en) Control of resistant pests
AU2021232737B2 (en) Pest Management
CN106535637B (en) Molecules having certain pesticidal utility, and intermediates, compositions, and methods related thereto
CN108349881B (en) Molecules having pesticidal utility, and intermediates, compositions and methods related thereto
CN115279189A (en) Compositions having pesticidal utility and methods relating thereto
CN108882704B (en) Molecules having pesticidal utility, and intermediates, compositions and methods related to these molecules
NZ760403B2 (en) Control of resistant pests
WO2023245257A1 (en) Improved pesticidal compositions and pest control methods
WO2022053640A1 (en) Mixtures containing calcium and magnesium phosphonate as pesticides