OA18495A - Mosquito vector control compositions, methods and products utilizing same. - Google Patents

Abstract

The present inventions concerns use of a certain methoxyacrylate compound to control mosquitoes, and vector control solutions comprising a defined methoxyacrylate compound, in particular the invention relates to a substrate, to a composition, for controlling mosquitoes comprising a defined methoxyacrylate compound, and to certain methoxyacrylate compounds.

Description

The présent Invention is in the technical field of insect vector control, particularly mosquito control, with a certain active methoxyacrylate compound. More specifically, the présent invention relates to methods of controlHng mosquitoes and to substrates, products, compositions and integrated mosquito management solutions for controlHng mosquitoes, each comprising the certain mosquitocidally active methoxyacrylate compound.

Mosquito control manages the population of mosquitoes to reduce their damage to human health, économies, and enjoyment. Mosquito control is a vital publlc-health practice throughout the world and especially In the tropics because mosquitoes spread many diseases, such as malaria (Wikipedia contributors, 'Mosquito control*, Wikipedla).

With the présent invention, it has now been found that certain methoxyacrylate compounds are mosquitocidally active (compared to similar anaiogous compounds) and are surpris!ngly useful for controlHng mosquitoes and for decreasing mosquito vector populations.

Accordingly, in a first aspect the présent invention provides for the use of one or more methoxyacrylate compounds selected from Table 1 below for controlHng mosquitoes.

In a second aspect, the présent Invention provides compositions, products, and treated articles (such as substrates or non-living materials) comprising a methoxyacrylate compound selected from the group consisting of the compounds shown In Table 1.

In a third aspect the présent invention provides integrated mosquito vector management or control solutions comprising one or more methoxyacrylate compounds selected from Table 1.

In a further aspect, a method of controlHng mosquitoes, preferably mosquito vectors of pathogenic disease, which comprises contacting a mosquito or Its environment with a composition comprising a mosquitocidally effective amount of a compound selected from the group consisting of from the compounds listed in Table 1, is made available.

Although certain methoxyacrylate compounds are known (see WO 90/07493, WO 92/18487, WO

95/05368, EP 0 242 081, WO 95/21153, EP 0 256 667, WO 2007/036710), the technical teaching from these documents is prlmanly directed to use of these compounds for control of fungi or Insects on plants and crops.

-2Further, WO 99/02150 describes defined β-alkoxyacrylates as being activa against chloroquinesensitive malaria pathogens, such as Plasmodium falciparum, and so such compounds are considered médicaments suitabie for treatment or prévention of malaria directly on the Individual or animal. In contrast, the présent invention is directed to controi of mosquitos that transmit the pathogens and vlruses causing diseases by using In a vector control solution one or more of the defined list of methoxyacryiata compounds, and thereby mitigate against the individual or animal being Infected/affected.

Mosquito-control operations are targeted against three different problème:

1. Nuisance mosquitoes bottier people around homes or in parks and recreatlonal areas;

2. Economicaily important mosquitoes reduce real estate vailles, adversely affect tourism and related business interests, or negatively impact iivestock or poultry production;

3. Public health is the focus when mosquitoes are vectors, or transmitters, of Infectious disease.

Many infectious diseases (e g. malaria, dengue and yellow fever, lymphatic filariasls, and ieishmaniasis) that are responsible for debilitating or even kiliing humans and animais in many countries, especially in tropical countries, are transmitted by insect vectors. For example, the mosquito parasite, Plasmodium falciparum, accounts for greater than 25 percent of childhood mortality outslde the néonatal period. In certain parts of Africa, malaria has been ranked first by the Worid Bank In terms of dlsability-adjusted life-years lost. A number of drugs are available to treat and/or prevent some insect-bome diseases. However, not ail diseases transmitted by mosquitoes can be treated efficiently. For example, there Is currently no chemotherapeutic drug or vaccine available against the Dengue virus. Furthermore, in the case of antimalarial drugs, treatment with the drugs currently available is becomlng less effective due to increased résistance in some Plasmodium strains. Plasmodium enfers the human bloodstream as a conséquence of the Insect bite and causes malaria. Therefore, one of the most effective ways to prevent mosquito vector-borne iilnesses Is by decreasing mosquito populations in areas of high pathogen transmission and/or preventing mosquito bltes In the first piace. More recentiy, efforts hâve been concentrated on controlilng the transmitting mosquitoes.

The three medlcally Important généra of insects which transmit diseases are the mosquitoes Anopheles, Culex and Aedes. The généra Culex and Aedes beiong to the sub-family Culicinae, while the Anopheles belongs to the sub-famlly Anophelinae.

Examples of diseases or pathogens transferred by the key mosquitoes are:

• Anopheles: malaria, filariasis;

• Culex: Japanese encephalitis, other viral diseases, filariasls; and

-3• Aedes: yellow fever, dengue fever, chikungunya, other viral diseases (e g Zika virus), and filariasis;

ln an attempt to reduce the problems associated with disease-transmitting mosquitoes, a wide range 5 of insecticides and insect repellents hâve been developed. Mosquitoes can be targeted with insecticides when they are in a larval state or once they hâve developed into adults. Accordingly, Insecticides which are used to kill larvae are termed larvicides whereas insecticides that are used to specifically target adult Insects are called adulticides. Most ofthe Insecticides commonly used to prevent the spread of disease are targeted against the adult mosquito and in particular against the 10 female adult mosquito.

The organochlorine DDT was the most widespread compound used woridwlde as an aduIticlde until it was withdrawn from use ln most areas. After that, organophosphates such as malathion, carbamates and propoxur were widely used in vector control programmes in most parts ofthe worid 15 and were steadily replaced by pyrethrolds, which became the mostly used adulticl de,

Organophosphates, such as plrimlphos-methyl are now being used again due to the development of pyrethrold résistance in many important vector species.

One of the most important problems associated with pyrethrolds, like their predecessors, is that 20 résistance has already developed ln many Insect species in several parts of the worid. Pyrethroid résistance, caused either by spécifie détoxification enzymes or an altered target site mechanism (kdr-type mutations In the sodium channels), has been reported in most continents ln the majority of medlcally important mosquitoes species, such as Anopheles gamblae in Africa and Aedes aegyptl in Asia. If résistance continues to develop and spread at the current rete, It may render such insecticides Ineffective in their current form ln the not too distant future. Such a scénario would hâve potentiaily devastating conséquences in public health terms, since there are as yet no obvious alternatives to many of the uses of pyrethroids.

Therefore, there is an ongoing search for insecticides for control of mosquitoes, especially for 30 mosquitoes having developed résistance, such as against pyrethroids.

The methoxyacrylate compounds useful ln the methods and other aspects of the Invention are listed ln Table 1 below:

Table 1 : methoxyacrylate compounds of the Invention

-9As well as the biological efficacy of the compounds of the présent Invention against moqusitos and résistant strains of such mosquitos, other considérations for selecting a suitable compound could Include Its safety (such as Its toxicity, persistence) to the environment, Including to the users of a vector control solution; Its suitability for making a vector control solution product (whether Indoor 5 residual spray formulation, mosquito net, or another type), Its suitability for adhérence and availability on a surface over a period of time (in the event the solution Is an indoor residual spray), and also its suitability for Incorporation Into a polymer product (such as a net) so that the compound would be readily available to control mosquitos on the surface of the net over a period of time and the nets can withstand multiple washings.

In an embodiment of each aspect ofthe présent Invention involving a vector control solution, the development of vector-bome diseases may be reduced by the mosquito control.

ln an embodiment of each aspect of the présent invention Involving a vector control solution, compounds 1 to 15,17,18,22 and 23 are preferred. ln a further embodiment, compounds 1,2,4, 5, 6,7, 8,9,10,11,12,13.15,18, and 22 are preferred. Especlaliy preferred are compounds 4,5,6, 7, 8,10,12,13 and 22. Advantageously preferred are compounds 7,8, and 13.

ln a further aspect, the présent Invention make available a methoxyacrylate compound selected from the group consisting of compounds 3, 5, 9, 11, 13, 14, 16, 17, 19, 20, 21 and 23; preferably, the compound Is selected from the group of compounds 3,5,9,11,13,14,17 and 23, especially preferred are compounds 5 and 13,

The methoxyacrylate compounds useful ln the methods and other aspects of the Invention can be 25 prepared similar to known procedures.

The oxlme compounds (e.g. compounds 1, 4, 12, 15, 18, 22) can be prepared analogously to procedures publlshed ln WO 9007493, WO 9218487 or Pesticide Science 1999, 55(2), 197-198. The key step is the reaction of an oxime with a benzylic compound containing a leaving group LG 1 under 30 basic conditions. LG 1 can be a halogen, preferably bromlne or chlorine. The base can be an Inorganlc sait, preferably NaîCOa, K2CO3, CszCOs or NaH. The reaction can be carried out neat or ln a solvent. Preferably the reaction is carried out in a solvent. The solvent can be MeOH, EtOAc, toluene, pentane, hexane, heptane, acetone, THF (tetrahydrofuran), NMP (N-methyl-2-pyrrolidon) or DMF (N.Ndimethylformamide). The substituent R In the oxime mlght be a C1-C6 alkyl group, a C1-C6 alkoxy 35 group, a N-C1-C6-alkyl amino group, N-C1-C6-aikoxy-1-C1-C4-alkylimine or an optionally substituted heterocycle (Scheme 1).

Scheme 1

Altematively N-hydoxy-phthalimide can be reacted with a benzylic compound containing a leaving group LG1 under basic conditions. LG 1 can be a halogen, preferably bromine or chlorine. The base 5 can be an inorganic sait, preferably NajCOj, K2CO3. CS2CO3, or NaH or EtaN. The reaction can be carried out neat or in a solvent. Preferably the reaction is carried out in a solvent. The solvent can be MeOH, EtOAc, toluene, pentane, hexane, heptane, acetone, THF (tetrahydrofuran), NMP (W-methyl2-pyrroiidon) or DMF (W,/V-dimethylformamide). The resuiting product is treated with hydrazine hydrate in methanol in order to liberate the amino functionaiity. The resulting product can then react 10 with a ketone or an imine In a solvent such as water, MeOH, EtOAc, toiuene, pentane, hexane, heptane, acetone, THF (tetrahydrofuran), NMP (N-methyl-2-pyrrolldon) or DMF (Λ/.Λ/dimethylformamide), preferably a mixture of water and MeOH. It mlght be advantageous to add a base such EbN or pyridine. The substituent R in the ketone or in the imine might be a C1-C6 alkyl group, a C1-C6 aikoxy group, a AFC1-C6-alkyl amino group, A/-C1-C6-aikoxy-1-C1-C4-alkylimine or an 15 optionally substituted heterocycle. The substituent R* in the amine might be hydrogen, alkyl or optionally substituted phenyl (Scheme 2).

Other methoxyacrylate compounds (such as compounds 16, 1Q 20, 21, 23) can be prepared by 20 reacting an aromatic ü-or 6-membered heterocyclic compound containing a hydroxy group with a benzylic compound containing a leaving group LG1 under basic conditions. LG 1 can be a halogen, preferably bromine orchiorine. The base can be an inorganic sait, preferably AgiCOs, NaîCO3, K2CO3,

Scheme 2

-11CsjCOs or Na H, most preferably AgzCOa. The reaction can be carried out neat or in a solvent.

Preferably the reaction is carried out in a solvent. The solvent can be MeOH, EtOAc, toluene, benzene, pentane, hexane, heptane, acetone, THF, NMP or DMF, preferably pentane, hexane or heptane (Scheme 3).

Scheme 3

Altematively an aromatic 5-or 6-membered heterocycllc compound containîng a leaving group LG 2 can be reacted under basic conditions with a benzytîc alcohol containîng a leaving group LG 3 in orthoposition. LG 3 can be a halogen, preferably lodine, bromine, chlorine. LG 2 can be a halogen, 10 preferably bromine, chlorine or fluorine or an alkyl sulfonyl group, preferably methylsulfonyl or an arylsulfonyl group, preferably phenylsulfonyl or tosyl. The base can be for example NaîCOa, K2CO3, CS2CO3, NaH, NaOMe. The solvent can be MeOH, EtOAc, toluene, benzene, pentane, hexane, heptane, acetone, THF, NMP or DMF. ln a second step the methoxyacrylate can be Introduced by a palladium catalyzed cross coupling reaction. LG 4 can be a boronic acid derivltave, e g. B(0H)2, or 15 metaliic group, e.g. Mg-Br or Znl or SnBu₄. The Pd catalyst can be for example Pd(PPh₄), Pd(0Ac)2 + P Plu (Scheme 4).

lg 2 lga

o

Scheme 4

Altematively the palladium catalyzed cross coupling reaction can be conducted ln a similar way having 20 the groups LG 3 and LG 4 reversed. LG 3 can be a halogen, preferably lodine, bromine, chlorine. LG can be a boronic acid derivltave, e.g. B(OH)î, or metallic group, e.g. Mg-Br or Znl or SnBiu. The Pd catalyst can be for example PdtPPtu), Pd(OAc)2 + PPh₄ (Scheme 5).

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• reducing contact - limiting exposure to mosquitoes can reduce infection risks significantly. For exarnple, bed nets, window screens on homes, or protective clothlng can help reduce the likelihood contact with mosquitoes. To be effective this requires éducation and promotion of methods among the population to raise the awareness of mosqulto threats.

· chemical control - insecticides, larvicldes, and repellents can be used to control mosquitoes.

For example, larvicldes can be used ln mosquito breeding zones; Insecticides can be applied to house walls or bed nets, and use of Personal repellents can reduce Incidence of mosquitoes bites and thus infection. The use of pesticides for mosqulto vector control Is promoted by the World Health Organization (WHO) and has proven to be highly effective.

· biological control - the use of natural mosqulto vector predators, such as bacterial toxins or botanical compounds, can help control mosqulto populations. Using fish that eat mosqulto larvae, has been demonstraited to hâve some success.

• population control through the release of sterillzed, or genetlcaliy modified, male mosquitoes has also been shown to control mosqulto vector populations and reduce infection risks.

A number of considérations Is taken into account when determining which methoxyacrylate compound would be suitable for use ln a particular mosqulto vector control strategy, such as favourable safety profile, biological performance and affordablilty.

ln one embodiment, the methoxyacrylate compounds shown ln Table 1 ln accordance with the methods and other aspects of the présent Invention are useful in controlling mosquitoes, in particular mosquitoes selected from tha genus Anopheles, Culex and Aedes. Examples include Aedes aegyptl, Aedes albopictus, Aedes Japonicas, Aedes vexans, Coquillettidia pedurbans, Culex molestus, Culex pallens, Culex plpiens, Culex quinquefasclatus, Culex restuans, Culex tarsalis, Anopheles alblmanus, Anopheles albitarsls, Anopheles ennularis, Anopheles aquasalis, Anopheles arebiensis, Anopheles aconltus, Anopheles atroparvus, Anopheles balabacensis, Anopheles coluzzii, Anopheles cullcifacies, Anopheles dariingl, Anopheles dirus, Anopheles fareutl, Anopheles flavirostrts, Anopheles fluviatilis, Anopheles freaboml, Anopheles funestus, Anopheles gambfae si.,

Anopheles koliensis, Anopheles labrenchiae, Anopheles lesteri, Anopheles leucosphyrus, Anopheles maculatus, Anopheles marejoare, Anopheles mêlas, Anopheles merus, Anopheles messeae, Anopheles minlmus, Anopheles mouchetl, Anopheles nill, Anopheles nuneztovari, Anopheles plumbeus, Anopheles pseudopunctipennis, Anopheles punctipennis, Anopheles punctulatus, Anopheles quadrimaculatus, Anopheles sacharovi, Anopheles sergentli, Anopheles sinensis, Anopheles stephensi, Anopheles subpictus, Anopheles sundalcus, Anopheles superpictus, and Mansonia titillans, Ochlerotatus stlmulans, Ochlerotatus japonices (each of which is an example of a mosqulto capable of carrylng or vectoring a pathogenlc disease).

-15By control is meant that a methoxyacrylate compound useful ln the methods and other aspects of the invention is employed ln a manner that kilis or repels the mosquito such that biting does not occur or in a manner that decreases mosquito populations such that biting does not occur as frequently.

In an embodiment, the methoxyacrylate compound selected from the group consisting of 4, 5,6,7,8,

10,12,13 and 22 is useful ln controliing one or more mosquitos selected from the genus Anopheles, Culex and Aedes, In particular one or more of Aecfes aegypti, Aedes alboplctus, Aedes japonlcas, Aedes vexans, Culex molestus, Culex pallens, Culex plplens, Culex qulnquefasdatus, Culex restuans, Culex tarsalis, Anopheles albimanus, Anopheles arabiensis, Anopheles coluzzii, Anopheles dariingi, 10 Anopheles dirus, Anopheles funestus, Anopheles gamblae si, Anopheles mêlas, Anopheles minlmus, Anopheles sinensis, Anopheles stephensl, Mansonia titillans.

ln an embodiment, the methoxyacrylate compounds of Table 1 are useful in the methods and other aspects of the invention to control adult mosqultoes.

ln another embodiment each of the methoxyacrylate compound 4, 5, 6, 7, 8,10, 12, 13 and 22 is especially useful in controlling one or more of the mosqultoes listed in table 2 below:

Compound no.	Mosquito species
4	Aedes aegypti |
4	Anopheles funestus |
4	Anopheles gambiae si |
4	Anopheles stephensi |
4	Anopheles arabiensis |
4	Aedes albopictus |
4	Anopheles coluzzii |
6	Aedes aegypti j
6	Anopheles funestus |
6	Anopheles gambiae si
6	Anopheles stephensi
6	Anopheles arabiensis
6	Aedes albopictus
6	Anopheles coluzzii
8	Aedes aegypti
8	Anopheles funestus \
8	Anopheles gambiae s. 1. \
8	Anopheles stephensi \
8	Anopheles arabiensis \
8	Aedes albopictus \
8	Anopheles coluzzii |

Compound no.	Mosquito species
5	Aedes aegypti
5	Anopheles funestus
5	Anopheles gamblae si
5	Anopheles stephensl
5	Anopheles arablensls
5	Aedes albopictus
5	Anopheles coluzzii
7	Aedes aegypti
7	Anopheles funestus
7	Anopheles gamblae si
7	Anopheles stephensl
7	Anopheles arabiensis
7	Aedes alboplctus
7	Anopheles coluzzii
10	Aedes aegypti
I 10	Anopheles funestus
| 10	Anopheles gambiae si
I 10	Anopheles stephensl
I 10	Anopheles arabiensis
I 10	Aedes albopictus
I 10	Anopheles coluzzii

12	Aedes aegyptl |
12	Anopheles funestus |
12	Anopheles gamblae si \
12	Anopheles stephensl \
12	Anopheles arabiensis \
12	Aedes alboplctus \
12	Anopheles colu22il
22	Aedes aegypti
22	Anopheles funestus
22	Anopheles gamblae si
22	Anopheles stephensl
22	Anopheles arabiensis
22	Aedes alboplctus
22	Anopheles colu22ii

13	Aedes aegyptl
’3	Anopheles funestus
13	Anopheles gamblae si
13	Anopheles stephensl
13	Anopheles arabiensis
13	Aedes alboplctus
1 n	Anopheles colu22ll

lnsecticide résistant mosquito species hâve also been detected end accordingly in an embodiment, a methoxyacrylate compound useful in the methods and other aspects of the Invention is suitable for controlling Insecticide-resistant mosquitoes, such as pyrethroid and/or carbamate-reslstant mosquitoes.

Pyrethroids are the only insectides that hâve obtained WHO recommendation against Malaria vectors on both Indoor Residuals Sprays (1RS) and Long Lasting Insecticldal Mosquito Nets (LLINs), in the form of Alpha-Cypermethrin, Bifenthrln, Cyfluthrln, Permethrin, Deltamethrin, Lambda-Cyhalothrin and Etofenprox. It has been the chemical class of choice ln agriculture and public health applications over the last several décades because of Its relatively low toxicity to humans, rapid knock-down effect, relative longevity (duration of 3-6 months when used as 1RS), and low cost. However, massive use of pyrethroids in agricultural applications and for vector control led to the development of résistance in major malaria and dengue vectors. Strong résistance has e.g. been reported for the pyrethroid Deltamethrin (and Permethrin) for the Anopheles gamblae Tlassalé (from southem Cote d'ivoire) strain (Constant V.A. Edi et al., Emerglng Infectious Diseases; Vol. 18, No. 9, September 2012). Pyrethroid résistance was also reported for Permethrin, Deitamethrin and Lambda-Cyhalothrin for the Aedes aegyptl Cayman Island strain (Angeia F. Harris étal., Am. J. Trop. Med. Hyg., 83(2), 2010) and AlphaCypermethrin, Permethrin and Lambda-Cyhalothrin for certain Anopheles strains (Wirt Van Bortel, Malaria Journal, 2008,7:102).

ln another embodiment of the Invention, the methoxyacrylate compounds of Table 1 can be suitable for use against Insecticide-resistant mosquitoes that are selected from Anopheles gambiae RSPH,

Anopheles gambiae Tiassalé, Anopheles gamblae Akron, Anopheles gamblae Kisuml Rdl,

Anopheles arabiensis NDjamlna, Anopheles coluzzll VK7, Anopheles funestus FUMOZ, Aedes aegypti Grand Cayman and Culex qulnquefasclatus strain POO.

-17Anopheles gamblae, strain RSPH Is a multi-resistant mosquito (target-site and metabolic-resistance) that Is described in the reagent catalog of the Malaria Research and Reference Reagent Resource

Center (www.MR4.org; MR4-number MRA-334).

Anopheles gamblae, strain Tiassalé is a multi-resistant mosquito (target and metaboiic-resistant strain) which shows cross-resistance between carbamates, organophosphates and pyrethrolds and is described in Constant VA Edi et ai., Emerging Infedious Diseases; Vol. 18, No. 9, September 2012 and Ludovic P Ahoua Alou et al., Malaria Journal 9:167,2010).

Anopheles gambiae, strain Akron Is a multi-resistant mosquito (target and metaboiic-resistant strain) and Is described in Djouaka F Rousseau et al., BMC Genomlcs, 9:538; 2008.

Anopheles coluzzil, strain VK7 Is a target-résistant mosquito and Is described in Dabire Roch 15 Kounbobr et al., Malaria Journal, 7:188,2008.

Anopheles funestus, strain FUMOZ is a metabolic -résistant strain and is described ln Hunt et al., Med Vet Entomol. 2005 Sep; 19(3):271-5). In this article it has been reported that Anopheles funestus - as one ofthe major malaria vector mosquitoes ln Africa - showed résistance to pyrethroids and carbamate 20 insecticides In South Africa.

Anopheles gamblae, strain Kisuml Rdl, a dleldrin résistant strain from Kenya.

Anopheles arabiensls, strain NDjamina, a pyrethroid résistant from Chad.

Aedes aegyptl, strain Grand Cayman is a target-resistant mosquito and is described in Angela F. Harris, Am. J. Tro. Med. Hyg. 83(2), 2010.

Culex qulnquefasciatus (metabolic -résistant to DDT strain P00); received from Texchem, Penang, 30 Malaysia.

Vector control solution are means to control a vector, such as a mosquito. Examples of such means are compositions, products, and treated articles, which include a substrate or non-iivlng material incorporating (e.g. coated or Impregnated with) a methoxyacrylate compound of Table 1, spray 35 products (e.g. indoor sprays, and aérosol products) comprising a methoxyacrylate compound of Table

1, paint compositions comprising a methoxyacrylate compound of Table 1, and products or treated articles comprising a methoxyacrylate compound of Table 1.

Examples of integrated mosquito vector management or control solutions of the Invention, such as 40 solutions for controlling mosquito bites or decreasing relevant mosquito populations, include the use

-18of such compositions, products, treated articles and substrates of the Invention at a locus of potential or known Interaction between the mosquito vector and an animal, Including a human, that Is susceptible to a pathogenic disease infection transmitted by such vector. Suitable Integrated solutions within the scope of the présent Invention also Include identifying mosquito breedlng sites and positioning compositions, products, treated articles and substrates of the Invention at such sites.

Examples of a substrate or non-llving material of the invention are self-supportlng film/sheet (e.g., screens), threads, fibres, yams, pellets, weaves (or textiles (e.g. for clothing)), nets, tents, end curtalns incorporating (e g. coated or Impregnated with) a methoxyacrylate compound of Table 1, which can 10 be used to protect against mosquito bites. In particular, it is well known that humans can be protected In their sleep from mosquito stings by insecticidaliy coated sleeping nets. Coated or Impregnated weaves of the Invention can also be used as curtains In front of Windows, doors open eaves, or ventilation openings, in order to control mosquito entering dwelllngs.

The use of a compound in a substrate of the présent Invention (e.g. nets and weaves) achieves at least one of the following objects:

• good insecticidal effect • fast-acting insecticidal efficacy • long-lasting Insecticidal efficacy • uniform release of active Ingrédient • long durability (including resisting multiple washings over an extended period) • simple production • safe to the user

The nets and weaves (or textiles) of the Invention that Incorporate (e.g. are coated or Impregnated with) a methoxyacrylate compound of Table 1 .are made up of a variety of naturel and synthetic fibres, also as textile blends In woven or non-woven form, as knit goods or fibres. Naturel fibres are for example cotton, raffia, jute, flax, sisal, hessian, wool, silk or hemp. Synthetic fibres may be made of polyamides, polyesters, polyacrylonitrlles, polyolefines, for example polypropylene or polyethylene, 30 Teflon, and mixtures of fibres, for example mixtures of synthetic and naturel fibres. Polyamides, polyolefins and polyesters are preferred as fibre material. Polyester, such a polyethylene terephthalate, are espedally preferred. Most preferred are nettings made from polyethylene and/or polypropylene.

The art discloses methods suitable for Incorporating (by way of coating) a compound onto nets and weaves (see for exampie, W02003/034823, WO 2008/122287, WO 01/37662, US2009036547, WO 2007/036710), from dipping or submerging them into a formulation of the insecticide or by spraying the formulation onto their surfaces. After treating the nets and weaves of the invention, they may be

-19dried simply at ambient températures (see also below for more back g round). Such methods are also suitable for incorporating (by way of coating) a methoxyacrylate compound of Tabie 1.

Also disclosed in the art are methods suitable for Incorporating by way of Impregnating a compound 5 within the net or weave by making polymer material in the presence of the methoxyacrylate, which is then extruded into fibres, threads or yams, for making the nets and weaves (see for example, W008004711,W02009/121580,WO2011/128380, WO2011/141260, WO2010/118743). Suchnets andweaves having availabieatthe surface ofthe netandweave an effective amount ofthe compound so as to control mosqulto bltes. Generaily the compound Is mixed with the molten polymer. Such 10 methods are also suitable for incorporating (by way of impregnating) a methoxyacrylate compound of

Table 1.

The term 'incorporating' or 'incorporated’ in context of the compound of the invention, additives and other insecticides is meant that the substrate or non-llvlng material comprises or contains the 15 respectively defined compound, additive and/or insecticide, such as by coating or imprégnation.

Preferably the substrate of the présent invention Is a net, which net is preferably a iong lastlng net, incorporated with a methoxyacrylate compound of of Table 1 by way of coating the net with a composition comprising a methoxyacrylate compound of Tabie 1, or by way of making a polymeric 20 materiai in the presence of such a methoxyacrylate compound and then processing the résultant polymeric material into an Inventive net.

ln accordance with the invention, when a methoxyacrylate compound of Table 1 is used within the polymer, then during use ofthe resulting net or weave made from the polymer, such methoxyacrylate 25 compound is released to the surface of the net to contrai against mosqulto bites - such contrai is sustained at adéquate ievel and for adéquate amount of time.

Examples of suitable polymers are polyamides, polyesters, polyacrylonitriles, polyolefines, such as polyethylene compositions that can be made from different polyethylene polymers; these may be 30 LDPE, LLDPE, MDPE and HDPE, LLDPE (Linear low-density polyethylene) is a substantially linear polymer (polyethylene), with significant numbers of short branches, commonly made by copolymerization of ethylene with longer-chain olefins. MDPE Is medium-density polyethylene Is a substantially linear polymer of polyethylene with shorter chain length than HDPE. HDPE (High-Density PolyEthylene) or PolyEthylene High-Denslty (PEHD) Is a polyethylene thermoplast. HDPE has little 35 branching, glving It stronger Intermolecular forces and tensile strength than lower- density polyethylene. It is also harder and more opaque and can withstand somewhat higher températures (120 degrees Cl 248 degrees Fahrenheit for short periods, 110 degrees centigrade /230 degrees Fahrenheit continuously). HDPE yarns are stronger than LDPE mixed polyethylene yams. LLDPE differs structurally from conventional low- density polyethylene (LDPE) because ofthe absence of long 40 chain branching. These polyethylene compositions (HDPE, LDPE, LLDPE and mixture thereof) are

-20generally used for preparing yams and polyethylene based textile products. Methods for incorporating an insecticide compound Into the polymer without weakening its resulting properties are known ln the art, such as using mixtures of HDPE and LDPE. Such methods can also be used to incorporate a methoxyacrylate compound of Table 11nto a polymer.

Examples of spray products of the présent invention are Indoor residual sprays or space sprays comprising a methoxyacrylate compound of Table 1. Indoor Residual Spraylng (1RS) is the technique of applying a residual deposit of an Insecticide onto indoor surfaces where vectors rest, such as on walls and cellings. The primary goal of Indoor residual spraylng is to reduce the lifespan of the 10 mosqulto vectors and thereby reduce or Interrupt disease transmission. The secondary impact Is to reduce the density of mosquitos within the treatment area. 1RS is a recognised, proven and costeffectlve Intervention method for the control of malaria and It is also used ln the management of Leishmaniasis and Chagas disease. Many malaria mosquito vectors are endophlllc, resting Inside houses after taking a blood meal. These mosquitoes are particularly susceptible to control through 15 indoor residual spraylng (1RS) comprising a methoxyacrylate compound of Table 1, As its name implies, 1RS Involves coating the walls and other surfaces of a house with a residual Insecticide. For several months, the methoxyacrylate compound will kilt mosquitoes that corne in contact with these surfaces. 1RS does not directly prevent people from being bltten by mosquitoes. Rather, It usually kills mosquitoes after they hâve fed, if they corne to rest on the sprayed surface. 1RS thus prevents 20 transmission of Infection to other persons. To be effective, 1RS must be applied to a very high proportion of households in an area (usually greater than 70 percent). Although the community plays a passive raie ln 1RS programs, coopération with an 1RS effort is a key to Its success. Community participation for 1RS often consists of cooperating with the spray teams by removing food and covering surfaces prior to spraylng and refraining from covering the treated surfaces with new paint or plaster. 25 However, community or Individual householder opposition to 1RS due to the smell, mess, possible chemical exposure, or sheer bother has become a serious problem ln some areas. Therefore, sprays ln accordance with the invention having good residual efficacy and acceptable odour are particularly suited as a component of Integrated mosquito vector management or control solutions.

ln contrast to 1RS, which requires that the active methoxyacrylate compound of Table 1 Is bound to surfaces of dwelilngs, such as walls, ceillng, space spray products of the invention rely on the production of a large number of smail insecticldal droplets Intended to be distributed through a volume of air over a given period of time. When these droplets Impact on a target mosquito, they dellver a léthal dose of the methoxyacrylate. The traditional methods for generating a space-spray Include 35 thermal fogging (whereby a dense doud of insecticide droplets is produced glving the appearance of a thick fog) and Uitra Low Volume (ULV), whereby droplets are produced by a cold, mechanical aerosol-generating machine.

Since large areas can be treated at any one time this method Is a very effective way to rapidly reduce 40 the population of flying mosquitoes in a spécifie area. Since there Is very limited residual activity from

-21the application it must be repeated at Intervals of 5-7 days in order to be fully effective. This method can be particularly effective In épidémie situations where rapid réduction In mosquito numbers Is required. As such, it can be used in urban dengue control campaigns.

Effective space-spraying is generally dépendent upon the following spécifie principes:

• Target insects are usualiy flying through the spray cloud (or are sometimes impacted whilst resting on exposed surfaces). The efficiency of contact between the spray droplets and target Insects is therefore crucial. This is achieved by ensuring that spray droplets romain aîrbome for the optimum period of time and that they contain the right dose of Insecticide.

These two Issues are largeiy addressed through optimizing the droplet size.

• If droplets are too big they drop to the ground too quickly and don't penetrate végétation or other obstacles encountered during application (llmiting the effective area of application). If one of these big droplets Impacts an individual insect then it 1$ also ‘overkill’ since a high dose witl be delivered per Individual insect.

· if droplets are too small then they may either not deposit on a target Insect (no Impaction) due to aerodynamlcs or they can be carried upwards into the atmosphère by convection currents.

• The optimum size of droplets for space-spray application are droplets with a Volume Médian Diameter (VMD) of 10-25 microns.

The compositions of the présent Invention may be made available in a spray product as an aerosolbased application, including aerosolized foam applications. Pressurised caris are the typical vehicle for the formation of aérosols. An aérosol propellant that is compatible with the Insecticide compound is used. Preferably, a liquefied-gas type propellant Is used. Suitable propeliants include compressed 25 air, carbon dioxide, butane and nitrogen. The concentration of the propellant in the methoxyacrylate composition Isfrom about 5 percent to about 40 percent by weight ofthe methoxyacrylate composition, preferably from about 15 percent to about 30 percent by weight of the methoxyacrylate composition.

In one embodiment, the methoxyacrylate formulation of the Invention can also Include one or more 30 foaming agents. Foaming agents that can be used Include sodium laureth sulphate, cocamide DEA, and cocamidopropyt betalne. Preferably, the sodium laureth sulphate, cocamide DEA and cocamidopropyt are used in combination. The concentration of the foaming agent(s) In the methoxyacrylate composition Is from about 10 percent to about 25 percent by weight, more preferably 15 percentto 20 percent by weightofthecomposition.

When the methoxyacrylate formulation Is used In an aérosol application not containing foaming agents), the composition of the présent invention can be used without the need for mixing directly prior to use. However, aérosol formulations containing the foaming agents do require mixing (i.e. shaking)

-22Immediately prior to use. ln addition, If the formulations containîng foaming agents are used for an extended time, they may require additional mlxlng at periodic Intervals during use.

A dweiling area may also be treated with the methoxyacrylate composition of the présent invention by 5 using a buming formulation, such as a candie, a smoke coil or a pièce of incense containîng the composition. For example, composition may be comprised In household products such as heated alrfresheners in which insecticidal compositions are released upon heating, for example, electrically, or by buming.

The compositions of the présent invention containîng a methoxyacrylate compound of Table 1 may be made available ln a spray product as an aérosol, a mosquito coil, and/or a vaporiser or fogger.

The concentration ofthe methoxyacrylate compound of Table 1 ln the polymeric material, fibre, yam, weave, net, or substrate, each of the Invention, can be varied within a relatively wide concentration 15 range from, fûr example 0.05 to 15 percent by weight, preferably 0.2 to 10 percent by weight, more preferably 0.4 to 8 percent by weight, especlally 0.5 to 5, such as 1 to 3, percent by weight.

The percentages mentloned above are based on dry weight of the net or substrate or non-livlng material.

Similarly, the concentration of the compound of the Invention ln the composition (whether for treating surfaces or for coating a fibre, yam, net, weave) can be varied within a relatively wlde concentration range from, for example 0.1 to 70 percent by weight, such as 0.5 to 50 percent by weight, preferably 1 to 40 percent by weight, more preferably 5 to 30 percent by weight, especially 10 to 20 percent by 25 weight.

The concentration shail be chosen according to the field of application such that the requirements conceming insecticidal efficacy, durability and toxlclty are met. Adapting the properties ofthe material can also be accomplished and so custom-tailored textile fabrics are obtalnable ln this way.

The methoxyacrylate compound of Table 1 when used ln the 1RS methods ofthe Invention Is présent on a surface of a dweiling at a coverage of from 0.01 to 2 grams of Ai per m2, preferably from 0.05 to 1 grams of Al per m2, especially from 0.1 to 0.7 grams of Ai per m2.

Accordlngly an effective amount of a methoxyacrylate compound of Table 1 can dépend on Its how Its been used, the mosquito against which control Is most desired and the environment its been used. Therefore, an effective amount of a methoxyacrylate compound of Table 1 Is sufficient that control of a mosquito Is achleved; ln case of.

• use as 1RS formulation, the effective amount Is such that coverage of the Al on the surface Is from 0.01 to 2 grams of Ai perm2, preferably from 0.05 to 1 grams of Al per m2, especially from 0.1 to 0.7 grams of Al per m2;

• use incorporatated within a net or substrate, the effective amount Is 0.05 to 15 percent by weight, preferably 0.2 to 10 percent by weight, more preferably 0.4 to 6 percent by weight, especially 0.5 to 5, such as 1 to 3, percent by weight

Generally the methoxyacrylate compound of Table 1 when used in certain products of the invention Is continuously distributed In a thread, yam, net or weave, but can also be partially or discontinuousiy 10 distributed ln a thread, yam, net or weave. For example, a net may contain certain parts which are coated or which is made-up of impregnated fibre, and certain other parts which are not; alternatively some of the fibres making up the net is impregnated, or Is coated, with the compound of the invention, and some of the other fibres not or these other fibres are impregnated, or are coated, with another Insecticide compound (see below).

Nets ofthe Invention Impregnated, orcoated, with a methoxyacrylatecompound ofTable 1 can satisfÿ the criteria of the WHOPES directive (see Guidelines for laboratory and field testing of longlasting Insectîcidal mosquito nets, 2005, http://www.who.int/whopes/guldelines/en/) for Insecticidecontaining iong-lasting mosquito nets up to 20 washes oniy, which means that such nets should not 20 lose their biological activity after just 20 wash cycles or so.

ln an embodiment, a net ofthe invention impregnated, or coated, with a methoxyacrylate compound of Table 1 can hâve biological activity in accordance with WHOPES guidelines of a knockdown after 60 minutes of between 95 percent and 100 percent or a mortality after 24 hours of between 80 25 percent and 100 percent after at least 20, such as 25, preferably at least 30 and even more preferably at least 35 washes.

The WHOPES directive Is to be understood as meaning the directive Guidelines for laboratory and field testing of Iong-lasting Insectîcidal mosquito nets, 2005). This directive is retrievabie at the 30 following Internet address: http://www.who.lnt/whopes/guidelines/en/.

When a net Is impregnated with a methoxyacrylate compound of Table 1 to prépare a net of the présent invention, the fibres making up the net are made by melting a polymer, a methoxyacrylate compound of Table 1 and optionally other compounds, such as other Insecticides, additfves, 35 stabilisera. When a net Is Impregnated with such a methoxyacrylate compound, then the net of the

Invention contains synthetic fibres; In contrast, a net of the invention coated with such a methoxyacrylate compound contains synthetic fibres and/or naturel fibres.

-24The polymeric materials useful in the compositions of the invention Incorporating a methoxyacrylate compound of Table 1 can be produced by mixing such a methoxyacrylate compound with the polymer in the liquid phase, and optionally other additives (such as binders and/or synergists), and other insecticidal compounds.

Methods of making suitable polymeric materials and then processing It are described ln the art - see for example, W009121580, WO2011/141260.

For example, nets based on an methoxyacrylate insecticide-containing polymeric material are produced by the following steps:

a) melting the polymer to be used and one or more insecticldally active ingrédients together or separately at températures between 120 and 250 degrees centigrade,

b) forming the melt of step a) into spun threads and cooling,

c) optionally leading the spun threads formed in step b) through a drawing system and drawlng and then optionally setting out the threads,

d) knittlng the spun threads to form a net,

e) subjecting the net to a heat-setting operation wherein the température for the heat-setting operation is chosen to be 20 degrees centigrade below the melting température of the polymer to be used.

The heat setting in step e) of the production of the nets is preceded by a washing step. Water and a detergent is preferably used for this. The heat setting is preferably carried out in a dry atmosphère.

Although the manufacture of the nets incorporated with the insecticide compound can occur in a single 25 location, it is also envlsaged that the different steps can take place in different locations. So a composition comprising a methoxyacrylate compound may be made which can then be processed Into a polymer. Accordilngly, the présent invention also provldes a composition comprising a methoxyacrylate compound of Table 1 in a concentrated form, which composition may aiso contain additives (such as binders and/or synergists), and other insecticidal compound(s) (which composition 30 had been prepared explicitly for making a polymer material impregnated with the methoxyacrylate compound of Table 1 (such a composition is often referred to as a masterbatch*)). The amount of the methoxyacrylate compound of Table 1 ln the masterbatch would dépend on the clrcumstances, but in general can be 10 to 95 percent by weight, such as 20 to 90 percent by weight, preferably 30 to 85 percent by weight. more preferably 35 to 80 percent by weight, especially 40 to 75 percent by 35 weight.

Also made available in the présent invention are compositions or formulations for coating walls, floors and ceilings inside of buildings and for coating a substrate or non-llvlng material, which comprise a methoxyacrylate compound of Table 1, The Inventive compositions can be prepared 40 using known techniques for the purpose in mind, which could contain a binder to facititate the

-25blnding of the compound to the surface or other substrate. Agents useful for binding are known ln the art and tend to be polymeric in form. The type of binder suitable for composition to be applied to a wall surface having particular porosities, binding characteristics would be different to a fibre, yam, weave or net - a skilled person, based on known teachlngs, wouid select a suitable binder.

Typical blnders are poly vinyl alcohol, modified starch, poly vinyl acrylate, polyacrylic, polyvinyl acetate co polymer, polyuréthane, and modified vegetable oils. Suitable blnders can include latex dispersions derived from a wide variety of polymers and co-poiymers and combinations thereof. Suitable latexes for use as blnders in the inventive compositions comprise polymers and copolymers 10 of styrene, alkyl styrenes, isoprene. butadlene, acryîonitrile lower alkyl acrylates, vinyl chloride, vinylldene chloride, vinyl esters of lower carboxylic acids and aipha, beta-ethylenically unsaturated carboxylic acids, including polymers containing three or more different monomer species copolymerized therein, as well as post-dlspersed suspensions of silicones or polyuréthanes. Also suitable may be a polytetrafiuoroethylene (PTFE) polymer for binding the active ingrédient to other 15 surfaces.

The formulation according to the present invention comprises at least one compound listed In Table (or a pesticide (A)), and a carrier, such as water (C), and optionaliy a polymeric binder (B) and further components (D).

The polymeric binder binds the methoxyacrylate compounds to the surface of the non-llving material and ensures a long-term effect. Using the binder reduces the élimination ofthe methoxyacrylate pesticide out of the non-living material due to environmental effects such as raln or due to human impact on the non-living material such as washing and/or cleanlng It. The further components can 25 be an additional Insecticide compound, a synergist, a UV stabiliser.

The inventive compositions can be in a number of different forms or formulation types, such as suspensions, capsules suspensions, and a person skiiled in the art can préparé the relevant composition based on the properties of the methoxyacryfate compound, its uses and also application 30 type.

For example, the methoxyacrylate compounds used in the methods and other aspects of the present invention may be encapsulated in the formulation. A encapsulated compound can provide Improved wash-fastness and also longer period of activity. The formulation can be organic based or aqueous 35 based, preferably aqueous based.

Microencapsulated methoxyacrylate compounds suitable for use in the compositions and methods according to the invention are prepared with any suitable technique known in the art. For example, various processes for mlcroencapsuiatlng material hâve been previously developed. These processes can be divided into three categories-physical methods, phase séparation and interfacial •26reaction. In the physical methods category, microcapsule wall material and core particles are physlcally brought together and the wail material flows around the core particle to form the microcapsule. In the phase séparation category, microcapsules are formed by emulsifylng or dispersing the core material in an immiscible continuous phase in which the wall material is dissolved and caused to physically separate from the continuous phase, such as by coacervation, and deposit around the core particles. In the Interfacial reaction category, microcapsules are formed by emulsifying or dispersing the core material in an immiscible continuous phase and then an Interfacial polymerization reaction is caused to taka place at the surface of the core particles. Tha concentration of the methoxyacryiata compound présent in the microcapsules can vary from 0.1 to 60% byweightofthe microcapsuie.

The formulation according to the invention may be formed by mixing ail ingrédients together with water optionally using suitable mixing and/or dispersing aggregates. In general, the formulation is formed at a température of from 10 to 70 degrees centigrade, preferably 15 to 50 degrees centigrade, more preferably 20 to 40 degrees centigrade.

It is possible to use a pesticide (A), solid polymer (B) and optionally additional additives (D) and to disperse them in the aqueous component (C).

If a binder Is présent In a composition of the présent Invention, It is preferred to use dispersions of the polymeric binder (B) in water as well as aqueous formulations ofthe pesticide (A) in waterwhich hâve been separately prepared before. Such separate formulations may contain additional additives for stabilizing (A) and/or (B) in the respective formulations and are commercially available. In a second process step, such raw formulations and optionally additional water (component (C)) are added.

Also combinations are possible, I.e. using a pre-formed dispersion of (A) and/or (B) and mixing It with solid (A) and/or (B).

A dispersion of the polymeric binder (B) may be a pre-manufactured dispersion already made by a chemicals manufacturer.

However, It is also within the scope of the présent invention to use hand-made dispersions, I.e. dispersions made in small-scaie by an end-user. Such dispersions may be made by providing a mixture of about 20 percent of the binder (B) in water, heating the mixture to température of 90 to 100 degrees centigrade and intenslvely stirring the mixture for several hours.

It Is possible to manufacture the formulation as a final product so that it can be readily used by the end-user for the process according to the présent Invention. However, it is of course also possible

-27to manufacture a concentrate, which may be diluted by the end-user with additional water (C) to the desired concentration for use.

ln an embodiment, a composition suitable for 1RS application or a coating formulation containing a methoxyacrylate compound of Table 1 contains the active ingrédient and a carrier, such as water, and may also one or more co*formulants selected from a dispersant, a wetter, an anti-freeze, a thickener, a preservatlve, an emulsifier and a binder or sticker.

The methoxyacrylate compound of Table 11s generally milled to a desired particle size, such as the particle size distribution d(0.5) is generally from 3 to 20, preferably 5 to 15, especially 7 to 12, gm.

Furthermore, It may be possible to ship the formulation to the end-user as a kit comprising at least • a first component comprising at least one compound listed in Table 1 (A); and • a second component comprising at least one polymeric binder (B).

• Further additlves (D) may be a third separate component of the kit, or may be already mixed with components (A) and/or (B).

The end-user may préparé the formulation for use by Just adding water (C) to the components of the kit and mixing.

The components of the kit may also be formulations in water. Of course It is possible to combine an aqueous formulation of one of the components with a dry formulation of the other component(s).

As an example, the kit can comprise • one formulation of a compound listed in Table 1 (A) and optionally water (C); and • a second, separate formulation of at least one polymeric binder (B), water as component (C) and optionally components (D).

Accordingly, in a further aspect the présent Invention provides a kit for treating a fibre, yam, net and weave by coating wash résistant insecticfdal properties thereto comprising: a first sachet comprising a pre-measured amount of at least one compound listed in Table 1, and a second sachet comprising a pre-measured amount of at least one polymeric binder. The resulting treated fibre, yam, net and weave has Imparted thereto the Insecticidal properties needed for vector control, such as to control vector-carrying mosquitoes.

The concentrations of the components (A), (B), (C) and optionally (D) will be selected by the skilled artisan dependlng of the technique to be used for coating/ treating.

-28ln general, the amount of pesticide (A) may be up to 50, preferably 5 to 50, such as 10 to 40, especially 15 to 30, percent by weight, based on weight of the composition.

The amount of polymeric binder (B) may be In the range of 0.01 to 30, preferably 0.5 to 15, more preferably 1 to 10, especially 1 to 5, percent by weight, based on weight of the composition.

If présent, In general the amount of additional components (D) Is from 0.1 to 20, preferably 0.5 to 15, percent by weight, based on weight of the composition. If présent, suitable amounts of pigments and/or dyestuffs are in general 0.01 to 5, preferably 0.1 to 3, more preferably 0 2 to 2, percent by weight, based on weight of the composition.

A typical formulation ready for use comprises 0.1 to 40, preferably 1 to 30, percent of components (A), (B), and optionally (D), the residual amount being water (C).

A typical concentration of a concentrate to be diluted by the end-user may comprise 5 to 70, preferably 10 to 60, percent of components (A), (B), and optionaliy (D), the residual amount being water (C).

The formulation of the présent invention may be applied to poiymeric material before their formation

Into the required products, e.g. while still a yam or In sheet form, or after formation of the relevant products.

For the case of nets and/or weaves, a process for coating nets and/or weaves at least comprising the following steps:

a) treating the nets and/or weaves with the aqueous formulation according to the invention by any of the procédural steps seiected from the group of (a1) passing the material through the formulation; or (a2) contacting the material with a roiler that is partly or fully dlpped Into the formulation and drawing the formulation to the side of the material in contact with the roiler, or (a3) submerging the material Into the formulation; or (a4) spraying the formulation onto the material; or (a5) brushing the formulation onto or into the material; or (a6) applying the formulation as a foam; or (a7) coating the formulation onto material.

b) optionally removing surplus formulation by squeezing the material between rollers or by means of a doctor blade; and

c) drying the material.

-29In case the raw materials containing residues of preceding production processes, e g. sizes, spin finishes, other auxiliaries and/or impurities, it may be bénéficiai to perform a washing step before the coating.

Specifically, the following details are Important for the steps a), b), and c).

Stepal)

The formulation Is applied by passlng the material through the aqueous formulation. Said step Is known by a person skilied In the art as padding. In a preferred embodiment the material Is completely submerged In the aqueous formulation either In a trough containing the liquor or the 10 material Is passed through the formulation which Is held between two horizontally oriented rollers. In accordance with the invention, the material may either be passed through the formulation or the formulation may be passed through the material. The amount of uptake of the formulation will be Influenced by the stability of concentrated baths, the need for level distribution, the density of material and the wish to save energy costs for drying and curing steps. Usual liquor-uptakes may be 15 40 to 150 percent on the weight of material. A person skilied In the art is famillar with determining the optimum value. Step al) is preferred for coating open-wldth material which is later tailored into nets.

For small-scale production or re-coating of non-treated nets, use of a simple hand-held roiler may be sufficient.

Step a2)

It Is further possible to apply the aqueous formulation on the material by a roller that Is partly dipped Into the dispersion thus applying the dispersion to the side of the material In contact with the roller (kiss-roltlng). By this method it Is possible to coat only one side of the material which Is advantageous if e.g. direct contact ofthe human skin with Insecticlde-treated material is to be avoided.

Coating of the material in step al), a2) or a3) Is typically carried out at températures from 10 to 70 degrees centigrade, preferably 15 to 50 degrees centigrade, more preferably 20 to 40 degrees centigrade

Step a4)

The spray may be applied in continuous processes or in batch-wise processes In suitable textile machines equipped with a spraying device, e.g. in open-pocket garment washer/extractors. Such 35 equipment is especiaily suitable for impregnating ready-made nets.

Step a6)

A foam comprises less water than the dispersion mentioned above. The drying process may therefore be very short. The treatment may be performed by Injectlng gas or blends of gas (e.g, air)

-30ïnto it. The addition of surfactants, preferably with fiIm-forming properties, may be required. Suitable surfactants and the required technical equipment are known to persons skilled in the art

Step a7)

A coating process may preferably carried out in a doctor-blade process. The process conditions are known to a person skilled in the art.

Step b)

The surplus émulsion is usually removed by squeezing the material, preferably by passlng the material through rollers as known in the art thus achleving a defined liquor uptake. The squeezed-off liquor may be re-used. Altematively, the surplus aqueous émulsion or aqueous dispersion may be removed by centrifuglng or vacuum suction.

Step c)

Drying may be performed at amblent températures. In particular, such a passive drying may be carried out in hot-dry cil mate. Of course, the drying process may be accelerated applying elevated températures. An active drying process would normally be performed during high scale processing. The drying is in general carried out températures below 200 degrees centigrade Preferred températures are from 30 to 170 degrees centigrade, more preferably at room température. The température choice Is determined by the thermal stability ofthe insecticide ln the formulation and the thermal stability of the non-livlng material impregnated.

For the method according to the Invention aqueous formulation comprising at least one pigment and/or at least one dyestuff may be used so that the material is not only coated with the methoxyacryiate pesticide but in addition also coloured at the same time.

ln a further aspect, the présent invention provides a method for treating a fibre, yam, net and weave by coating wash résistant insecticfdal properties thereto comprising (I) preparing a treatment composition, which comprises at least one compound listed ln Table 1, (ii) treating said fibre, yam, 30 net and weave and (iii) drying the resulting treated a fibre, yam, net and weave.

The polymerlc binder (B) can be dispersed in an aqueous formulation and comprises one or more fluorinated acrylic copolymers useful in the water and oïl résistant formulations includes copolymer prepared by the polymerization of a perfluoroalkyi acrylate monomer and a comonomer, especlally an acryiate monomer. The binder may also be fluorocarbon resins (as described in WO 2006/128870.

Only water is used as solvent for the formulation. However, trace amounts of organic solvents miscible with water may be présent. Examples of soivents comprise water-miscible alcohols, e g.

monoalcohois such as methanol, éthanol or propanol, higher alcohols such as ethylene glyeol or

-31polyether polyols and ether alcohols such as butyl glycol or methoxypropanol. Preferably the content of an organic solvent is no more than 5 percent by weight (based on component (C), more preferably no more than 1 percent by weight (based on component (C), ln particular no more than

0.1 percent by weight, based on component (C).

Depending on the Intended use of the non-living material to be treated the formulation according to the présent invention may further comprise one or more components or additives (D) selected from preservatives, détergents, Allers, impact modifiera, antl-fogglng agents, blowing agents, clarifiera, nucleating agents, coupling agents, fixative agents, cross-linklng agents, conductivity-enhanclng 10 agents (antistats), stabillzers such as antloxidants, carbon and oxygen radical scavengers and peroxlde decomposlng agents and the like, flame retardants, mould release agents, agents having UV protecting properties, spreading agents, antl-blocking agents, antl-mlgrating agents, foamforming agents, anti-soiling agents, thickeners, further biocldes, wetting agents, plasticizers and filmforming agents, adhesive or antl-adheslve agents, optical brightening (fluorescent whitening) agents, 15 pigments and dyestuffs.

A typical amount of the polymeric binder (B) Is from 0.01 to 10 percent by weight (dry weight) of the (dry) weight of the material. As a general guidellne, the weight ratio between insecticide and binder (B) should approximately be constant with a value depending on the insecticidal and migratory ability 20 of the Insecticide, i.e. the higher the amount the Insecticide the higher also the amount of binder (B).

Preferred amounts of binder (B) are from 0.1 to 5 percent by weight, more preferably 0.2 to 3 percent by weight of the (dry) weight of the material.

The coated material can comprise at least one pigment and/or at least one dyestuff. The amount of 25 the at least one pigment and/or dyestuff is In general from 0.05 to 10 percent by weight, preferably

0.1 to 5 percent by weight, more preferably 0.2 to 3.5 percent by weight of the (dry) weight of the material.

The method of coating or treating the non-living material is not limited to a spécifie technology.

Coating may be performed by dipping or submerging the non-living substrate into the formulation or by spraylng the formulation onto the surface of the non-living material. After treating the treated nonliving substrate may be dried simply at ambient températures.

Accordingly, no sophisticated technology is necessary for the coating, and therefore the coating 35 process may be carried out by the end-user itself ln at low-scale.

For instance, a typical end-user may coat/treat a net itseif, e.g. within its household, using the formulation according to the présent invention. For this purpose, it is in particular advantageous to use a kit as herein defined.

-32In an embodiment, the présent invention provides a polymer, a fibre, a thread, a yam, a net or weave comprising one or more compounds ofthe invention (listed in Table 1), where also Incorporated can be one or more other customary materials used to make such a polymer, and the polymer, a fibre, a thread, a yam, a net or weave optionally can further Incorporate one or more 5 other Insecticides and/or synergists.

In an embodiment, the présent invention provides a net or weave incorporated with one or more methoxyacrylate compounds (listed In Table 1), which optionally further Incorporâtes one or more other insecticides and/ or synergists.

As described in the art. the methoxyacrylate compound of Table 1 useful In the methods and other aspects of the présent Invention can be used alone or in combination with another insecticide, synergist, insect repellent, chemosterilant, flame retardant, UV protector/ absorber, and/or additives for controlling release characteristics.

When used In accordance with the invention, the methoxyacrylate compounds of Table 1 may be used alone to control a mosquito or used in combination with one or other known insecticides and/or one or more additives (such as synergists) - in polymers for making non-living substrates, such as nets and weaves, for formulations for treating non-living substrates, such as nets and weaves, in 20 1RS products and space-spraying products.

In an embodiment, the présent Invention provides a composition (useful for coating a polymeric material or a product therefrom, or a useful as a spray product) comprising one or more compounds of the Invention, which optionally further comprises one or more other Insecticide and/or synergists 25 and one or more other additives.

Examples of synergists are plperonylbutoxide (PBO), sebacic esters, fatty acids, fatty acid esters, vegetable oils, esters of vegetable oiis, alcohol alkoxylates and antloxidants.

Suitable sebacic esters are for example dimethyl sebacate, diethyl sebacate, dibutyl sebacate, dibenzyl sebacate, bis(N-succinimidyl)sebacate, bis(2-ethylhexyl)sebacate, bis(1-octyloxy-2,2,6,6tetramethyt-4-piperidyt)sebacate, bis(2,2,6,6-tetramethyt-4-piperidyt)sebacate and ^5(1.2,2,6.6pentamethyl-4-piperidinyl)sebacate (BLS292).

Suitable fatty acids are (preferably mono- or polyunsaturated) fatty acids having a chain length of 12 to 24 carbon atoms, for exampie palmitoleic acid, oleic acid, elaldic acid, vaccenlc acid, Icosenlc acid, cetoleic acid, erucrc add, nervonic acid, llnoleic acid, alpha-linolenic add, gamma-llnolenlc acid, arachidonic add, timnodonlc acid, clupanodonic acid and cervonlc add. Particular preference is given to oleic add, linoleic add, alpha-linolenic acid and gamma-iinolenic add.

-33Suitable fatty acid esters are preferably methyl or ethyl esters of the above-recited fatty acids.

Methyl esters are particularly preferred. Fatty acids and their esters can each also be présent in mixtures.

Useful vegetable oils Include ali plant-dertvable oils customarily usable in agrochemical compositions. As examples there may be mentioned sunflower oil, rapeseed oil, olive oil, castor oil, colza oil. maize kernel oil, cottonseed oil and soybean oil. Rapeseed oil is preferred.

Suitable esters of vegetable oils are methyl or ethyl esters ofthe above-recited oils. Methyl esters 10 are preferred.

Antloxldants useful as additives Include for example butylhydroxytoluene, butylhydroxyanisole and L-ascorblc acid.

Plant essentiaî oils may also be used în an indoor residual spray compositions; examples are those selected from citranella, peppermint oil, d-limonene and abies sibirica. These plant essentiaî oil materials are known and used for other uses and can be prepared by a skilled artisan by employing known methods and also are available commercial! y.

ln addition to at least one defined active Ingrédient from the group of methoxyacrylate (a compound listed in Table 1), the methods, compositions, polymer, product, substrate and/or Integrated mosqulto management solution according to the invention may contain one or more further Insecticidally active ingrédients. Particularly examples are one or more active Ingrédients from the class of organophosphates, pyrethroids, carbamates or neonicotinold, and also DDT, Indoxacarb, nicotine, bensultap, cartap, spinosad, camphechlor, chlordane, endosulfan, gamma-HCH, HCH, heptachlor, lindane, methoxychlor, acetoproie, ethiproie, fipronil, pyrafîuprole, pyriprole, vaniliprole, avermectin, emamectin, emamectin-benzoate, Ivermectin, milbemycln, diofenolan, epofenonane, fenoxycarb, hydroprene, klnoprene, methoprene, pyriproxifen, triprene, chromafenozide, halofenozide, methoxyfenozide, tebufenozide, bistrifluoron, chlofluazuron, diflubenzuron, fluazuron, 30 flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, novlflumuron, penfluoron, teflubenzuron, triflumuron, buprofezin, cyromazlne, diafenthluron, azocyclotin, cyhexatin, fenbutatinoxide, chlorfenapyr, binapacyrl, dinobuton, dinocap, DNOC, fenazaquin, fenpyroximate, pyrimidtfen, pyridaben, tebufenpyrad, tolfenpyrad, hydramethylnon, dicofol, rotenone, acequinocyt, fluacrypyrim, Bacillus thuringiensls strains, spirodiclofen, spiromesifen, splrotetramat, 3-(2,5-dimethylphenyl)-835 methoxy-2-oxo-1 -azaspiro[4.5]dec-3-en-4-yl ethyl carbonate (alias: carbonic acid. 3-(2,5dimethylphenyl)-8-methoxy-2-oxo-1-azasplro[4.5]dec-3-en-4-yl ethyl ester, CAS-Reg -No.: 38260810-8), flonicamid, amitraz, propargite, flubendiamide, chloranthraniiiprol, thiocyclam hydrogen oxalate, thiosultap-sodium, azadirachtin, Bacillus spec., Beauveria spec., Metarrtizlum spec., Paecilomyces spec., Thuringiensin, Verticillium spec., aluminium phosphid, methylbromîde,

-34sulfurylfluorid, cryolite, flonlcamld, pymetrozlne, dofentezlne, etoxazole, hexythiazox, amldoflumet, bendothiaz, benzoximate, bifenazate, bromopropylate, buprofezin, chinomethionat, chlordimeform, chlorobenzilate, chloroplcrin, clothlazoben, cycloprene, cyflumetofen, dicyclanil, fenoxacrim, fentrifanil, flubenzimine, flufenerim, flutenzin, gossyplure, hydramethylnone, japonilure, metoxadiazone, petroleum, piperonylbutoxid, kaliumoieat, pyridalyl, suifluramld, tetradifon, tetra su I, triarathene and verbutin.

In a further aspect, the présent invention provides a method for protecting a mammal, Induding a human, against mosquitoes, the method comprising applying to the mosquito or to a locus of potentlal or known interaction between the mammal and the mosquito, a vector control solution comprising a mosquitoddally effective amount of a compound selected from the group consisting of a methoxyacrylate compound as defined In Table 1.

Another asped of the invention Is a method for controlling the spread of a vector-bome disease, comprising: identifying an mosquito vector; and contacting the mosquito vector or its environment with a vector control solution comprising a mosquitocldaily effective amount of a compound seleded from the group consisting of a methoxyacrylate compound as defined In Table 1.

An asped ofthe invention also includes a mosquitocldal method which comprises contacting a mosquito or its environment with a vector control solution comprising an mosquitocldaily effective amount of a compound selected from the group consisting of a methoxyacrylate compound as defined in Table 1.

The présent invention also provides a method, comprising: (i) identifying a locus of potential or known Interadion between a mosquito vector and a mammal, induding a human, susceptible to pathogenic disease infection when contacted by such vector and (il) positioning a vector control solution at the locus, wherein the solution includes a mosquitoddally effective amount of a compound selected from the group consisting of a methoxyacrylate compound as defined in Table 1.

The présent Inventon through control of mosquitos would also be expected to control the many viruses carried by such vedors. As an example, control of the mosquitos of the genus Aedes by use of one or more of the defined compounds Table 1, as part of a vector control solution, may control the Zika infections. Examples of mosquitos reported to spread the Zika virus are the Aedes mosquitoes, such as Aedes aegyptl and Aedes albopictus. Accordingly, in an aspect, the présent

Invention provide a method of controlling Zika virus infection, wherein one or more of the defined compounds Table 1 is présent In a mosquitoddally effective amount in the viclnity of Aedes mosquitoes, such as Aades aegypti and Aedes albopictus. ln the vicinity of the mosquitoes Is meant areas where mosquitos are likely to be présent, such as ln the environment ln general, spectficaliy in a room, or at the site of a mosquito biting an Individual or mammal, for example, on the skin surface.

-35ln each of the methods according to présent invention, the vector control solution Is preferably one or more of a composition, a product and a treated article, each comprising a compound selected from the group consisting of a methoxyacrylate compound as defîned ln Table 1.

*

A ‘fibre* as used in the présent invention refers only to a fine, threadlike plece, generally made of natural material, such as cotton, or jute.

ln each aspect and embodiment ofthe invention, 'consisting essentially* and Inflections thereof are a preferred embodiment of *comprlsing* and its inflections, and ‘consisting of* and inflections thereof are a preferred embodiment of‘consisting essentiaiiy of* and its inflections.

The disclosure ln the présent application makes available each and every combination of embodiments disclosed herein.

The following Examples serve to lllustrate the Invention. They do not limit the Invention.

Températures are given ln degrees Celsius; mlxlng ratios of solvents are given In parts by volume.

The Examples which follow serve to lllustrate the invention. The compounds of the Invention can be dlstlnguished from other similar compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled ln the art using the experimental procedures outlined in the Exemples below, using lower concentrations If necessary, for exampie 10 ppm, 5 ppm, 2 ppm, 1 ppm or 0.2 ppm; or lower application rates, such as 300,200 or 100, mg of Al per m2.

EXAMPLES

Préparation examoies:

EXAMPLE 1 : Préparation of methyl (E1-2-r2-f(5-tert-butvl-1.3.4-oxadtazol-2-vl)oxvlphenvll-3-methoxv30 prop-2-enoate (compound 2)

Step 1: 2-tert-butyl-5-(p-tolylsuifonyl)-1,3.4-oxadiazole o

To a solution of KMnO< (1.67 grams, 1.3 equiv., 10.47 mmol) ln water (150 ml) was added dropwise a solution of 2-tert-butyî-5-(p-tolylsuifanyl)-1,3,4-oxadiazoie (2 g, 8.06 mmol) ln glacial acetic acid (30 35 ml). After 2 h an aqueous solution of sodium metablsulphite was added until the mixture was

36decolorized. The mixture was filtered and the solid was washed with water, then recrystallized from éthanol to give 2-tert-butyl-5-(p-tolylsulfonyl)-1,3,4-oxadiazole (1.00 g, 3.57 mmol, 44%yield).

Step 2: Methyl (E)-2-[2-[(5-tert-butyl-1,3,4-oxadiazol-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate

To a solution of methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (100 mg, 0.48 mmol; prepared as described ln Example 3 of EP 0242081 A) in DMF (2 ml) at 0 *C was added 2-tert-butyl5-(p-tolylsulfonyl)-1,3,4-oxadiazole (404 mg, 3 equiv., 1.44 mmol) and KjCOs (2 equiv., 0.98 mmol). The mixture was allowed to warm to room température and stirred for 72 h. The mixture was partitloned between diethyl ether and water. The aqueous layer was extracted two times with ether. The combined organic layers were washed with water and brine, dried with MgSO«, filtered and concentrated under reduced pressure. Column chromatography 100% cyclohexane to cyclohexane/ethyl acetate (70:30) gave methyl (E)-2-[2-[(5-tert-butyl-1,3,4-oxadiazo!-2-yl)oxy]phenyl]3-methoxy-prop-2-enoate (102 mg, 0.30 mmol, 64% yield).

EXAMPLE 2; Methvl(E)-3-methoxv-2-f2-n(E)-r(2E)-2-methoxvimino-1-methvl-butvlidene1aminoloxvmethvllDhenvllDroD-2-enoate (compound 4)

Step 1: (2E)-2-Hydroxyiminopentan-3-one

OH

To a solution of pentan-3-one (8 g, 69.7 mmol) In toluene (30 ml) at 0 C was added hydrogen chloride (2 mol/L) in diethyl ether (35 ml, 1 equiv., 69.7 mmol, 2 mol/L) dropwise. After the addition was complété a solution of isoamylnitrite (10.7 ml. 1.1 equiv., 76 63 mmol) in diethyl ether (20 ml) was added dropwise. The mixture was stirred at 0 *C for 2 h, then allowed to warm to room température and stirred for 16 h. Water (25 ml) was added and the mixture was extracted three times with 2M NaOH. The combined aqueous layers were made slightly acidic with 2M HCl and extracted three times with dichloromethane. The combined organic layers were dried with MgSO«, filtered and concentrated under reduced pressure to give (2E)-2-hydroxyiminopentan-3-one (5.27 g, 45.8 mmol, 66% yield).

Step 2: (3E)-3-Methoxyiminopentan-2-one oxirrre

-37To a solution of (2E)-2-hydroxyiminopentan-3-one (2.8 g, 24 mmol) in toluene (30 ml) was added methoxyamine hydrochlorid (40% in H2O) (1.2 equiv., 29 mmol). The mixture was heated to 65 ’C and triethyfamine (1.75 equiv., 43 mmoi) was added dropwise. The mixture was heated at 65 *C for 3 h. The mixture was cooled to room température and acidified with conc. HCi. The organic layer was coliected and extracted three times with 2 M NaOH. The combined extracts were made acidic with conc. HCi and extracted three times with ethyl acetate. The combined organic layers were dried with MgSO4, filtered and concentrated. Column chromatography 100% dichloromethane to dlchloromethane/methanol (90:10) gave (3E)-3-methoxyiminopentan-2-one oxime (2.2 g, 15 mmol, 63% yield).

Step 3: Methyl (E)-3-methoxy-2-[2-[[(E)-[(2E)-2-methoxyimino-1-methyi-butylidene]amino]oxym ethyf]phenyf]prop-2-enoate

To a stirred solution of methyl (E)-2-[2-(bromomethyl)phenyf]-3-methoxy-prop-2-enoate (2.5 g, 8.8 mmol; prepared as in J. Agric. Food. Chem, 2007,55, 5697-5700) in acetone (8 mi) was added (3E)3-methoxyiminopentan-2-one oxime (1.5 g, 1.2 equiv., 11 mmoi) and K2CO3 (1.8 g, 1.5 equiv., 13 mmol). The mixture was heated to 60 *C for 72 h. The mixture was cooled to room température, filtered and concentrated under reduced pressure. Column chromatography 100% cyclohexane to cyclohexane/ethyf acetate (80:20) gave methyl (E)-3-methoxy-2-p-[[(E)-[(2E)-2-methoxyimino-1methyl-butylidene]amino]oxymethyi]-phenyl]prop-2-enoate (1.8 g, 5.2 mmol, *59% yield). Mlnor Impurities were removed by a second chromatography: 100% dichloromethane to dichloromethane/ethyi acetate (95:5).

EXAMPLE 3: Methyl (E)-2-P-f(4-tert-butvl-1.3.5-triazin-2-vDoxvlDhenvl1-3-methoxv-Drot>2-enoate (compound 5)

Step 1: N'-cyano-2,2-dimethyl-propanamldine

The HCl sait of 2,2-dimethylpropanamldine (2.5 g, 18.3 mmol) was dissolved in water (8 ml) and sodium hydrogencyanamide (1.17 g) was added. The mixture was stiired at room température for 4

38h. The solid was filtered in dried in vacuum to give N'-cyano-2₎2-dimethyt-propanamidine (1.17 g, 9.3 mmol, 51%).

Step 2: 2-tert-butyl-4-chloro-1,3,5-triazlne

POCh (1.54 g) was added into dry acetonitrile (10 ml). Dry DMP was added dropwise over 10 minutes. Then N'-cyano-2,2-dimethyl-propanamldine (1.17 g, 9.3 mmol) in dry acetonitrile (25 ml) was added over a period of 25 minutes and the resulting mixture was stirred for 4.5 h at room température. The mixture was poured into water (100 ml) and extracted with CH2CI2 (4 x 40 ml). The combined organic phases were dried with MgSO<, filtered and concentrated to provide 2-tert-butyl-4-chloro-1,3,5-triazine as an oil (1.15 g, 6.7 mmol. 72%).

Step 3: Methyl (E)-2-t2-[(4-tert-butyl-1,3.5-triazln-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate

To a stirred solution of methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (1.54 g, 7.4 mmol; prepared as described in Example 3 of EP 0242081 A) in DMP (25 ml) was added under cooling (~O’C) potassium carbonate (930 mg) followed by addition of 2-tert-butyt-4-chloro-1,3₎5-triazlne (1.15 g, 6.7 mmol). The reaction mixture was stirred at ~0°C for 1.5 h. The reaction mixture was poured into water and extracted with diethyl ether. The organic layer was dried over NaîSCh, filtered and concentrated. The crude reaction mixture was then purified by column chromatography using ethyl acetate-hexane (1:3) to give methyl (E)-2-[2-[(4-tert-butyt-1,3,5-triazin-2-y1)oxy]pheny1]-3-methoxyprop-2-enoate (330 mg, 0.96 mmol, 14%).

EXAMPLE 4: Methyl fE)-3-methoxv-242-fî5-(trifluoromethvl)-1.3.4-thladiazol-2-vnoxvlphenvl1-orop-2enoate (compound 6)

Step 1: 2-Bromo-5-(triffuoromethyl)-1,3,4-thiadiazole

To a stirred solution of 5-(trifluoromethyi)-1,3,4-th1adiazol-2-amine (5.0 g, 29.5 mmol) in aqueous HBr was added a solution of sodium nitrite (4.48 g, 64.97 mmol) in 125 ml water dropwise at 0 *C during 2 h and stirred for another 2 h. The reaction was diluted with ethyl acetate and brine. The ethyl acetate layer was separated and the aqueous part was washed twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude compound was then purified by flash chromatography using 15% ethyl acetate / hexane to give 2bromo-5-(trifluoromethy1)-1,3,4-thladlazole (1.2 g, 5.1 mmol, 17% yield).

Step 2: Methyl (E)-3-methoxy-2-p-[I5-(trifluoromethy1)-1,3,4-thiadiazol-2-y1]oxy]pheny1]-prcp-2enoate

F-

To a stirred solution of 2-bromo-5-(trifIuoromethy1)-1,3,4-thiadiazole (710 mg, 3.41 mmol) in 10 mi DMF methyl (E)-2-(2-hydroxyphenyi)-3-methoxy-prop-2-enoate (1.19 g, 5.12 mmol; prepared as described in Example 3 of EP 0242081 A) was added followed by potassium carbonate. The réaction mixture tumed brownish. TLC showed complété consumptlon of starting material after 3 days. The reaction was partitioned between ethyl acetate (50 ml) and water (50 ml). The organic layer was washed subsequently with water (20 ml) and brine (20 ml). The organic layer was dried over NajSCU, filtered and concentrated. The crude reaction mixture was then purified by column chromatography using 20-30 % ethyl acetate-hexane to give methyl (E)-3-methoxy-2-[2-[[5-(trifluoromethy1)-1,3,4thiadiazol-2-yi]oxy]phenyi]-prop-2-enoate (1.1 g, 3.0 mmol, 88 % yield).

EXAMPLE 5' Methvl (E)-2-f2-f(3-tert-butvl-1.2.4-thladiazol-5-v»oxvlDhenvl1-3-methoxv-DroD-2-enoate (compound 7)

Step 1:3-tert-Butyl-5-chloro-1,2,4-thiadiazole

Cl

-40To a stirred solution of the HCl sait of 2.2-dimethylpropanamldine (1.6 g, 11.8 mmol) In dichloromethane (30 ml) at-15 ’C was added trichloromethyl thiohypochlorite (2.0 g, 10.8 mmol) and aqueous sodium hydroxide solution (2.36 g. 59 mmoi; dissolved ln 12 ml water) slowly. After addition, the température of the reaction mixture was slowly ralsed to room température and stirring was continued for 3 h. The reaction mixture was diluted with dichloromethane and washed with water (50 ml x 3). The combined organic layer was dried over Na2SO<, filtered and concentrated under reduced pressure to give 3-tert-butyl-5-chloro-1,2,4-thiadiazole (1.7 g, 9.6 mmol, 89 % yield).

Step 2: 3-tert-Butyl-5-methylsulfbnyl-1,2,4-thiadiazole

To a stirred solution of S-tert-butyl-S-chloro-li^-thiadlazole (260 mg, 1.47 mmol) ln ethylene glycol mono ethyl ether (2 ml) was added at room température sodium methanesulfinate (150 mg, 1.47 mmol). After the addition the température of the reaction mixture was slowly raised to 100 ’C and stirring was continued for 1 h. The réaction was monitored by TLC and after the completion of the reaction the mixture was allowed to cool down to room température. The reaction mixture was partitioned between water (5 ml) and CH2CI2 (10 ml). The organic layer was dried over Na2SO«, filtered and concentrated under reduced pressure to give the crude material. The crude material was purified by column chromatography using 15 - 20 % ethyl acetate / hexane as an eluent to afford 3-tert-butyl5-methylsulfonyl-1,2,4-thiadiazole (325 mg, 1.48 mmol,quantitative yield).

Step 3: Methyl (E)-2-[2-[(3-tert-butyl-1,2,4-thiadiazol-5-yl)oxy]phenyll-3-methoxy-prop-2-enoate

To a stirred solution of methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (100 mg, 0.48 mmol;

prepared as described in Example 3 of EP 0242081) In dry DMP (2 ml) were added 3-tert-butyl-5methylsulfbnyl-1,2,4-thladiazole (127 mg, 0.57 mmol) and K2CO3 (100 mg, 0.72 mmoi) at room température and stirring was continued for 17 h. The reaction was monitored by TLC and after completion of the reaction the mixture was partitioned between ethyl acetate (10 ml) and brine (10

-41ml). The organic layer was dried over NaîSCh, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography using 15-20 % ethyl ecetate / hexane as an eluentto give methyl (EJ-2-[2-[(3-tert-butyt-1,2,4-thiadiazol-5-y1)oxy]phenyl]-3-metfioxy-prop-2-enoate (90 mg; 0.26 mmol 54 % yield).

EXAMPLE 6: Methyl (E)-2-f2-rî4-ftrifluoromethvl¹l-2-DVridvlloxvfDhenvl1-3-methoxv-DroD-2-enoate (compound 8)

Step 1: Methyl (E)-2-(2-[[6-chloro-4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate

To a solution of 2-chloro-6-fluoro-4-(trifluoromethyl)pyridlne (184 mg, 1.1 equiv., 0.924 mmoi) In DMF (5 ml) at room température was added methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2enoate (175 mg, 0.84 mmol; prepared as described in Example 3 of EP 0242081 A) and K2CO3 (174 mg, 1.5 equiv., 1.26 mmol). The mixture was stirred at room température for 16 h. The mixture was partitloned between diethyl ether and water. The aqueous layer was extracted twice with ether. The combined organic layers were washed with water and brine, dried with MgSO4, filtered and concentrated under reduced pressure. Column chromatography cyclohexane 100% to cyclohexane/ethyl acetate (80.20) gave methyl (E)-2-[2-[[6-chloro-4-(trifluoromethyl)-2pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate (170 mg, 0.439 mmol, 52% yield).

Step 2: Methyl (E)-2-[2-[[4-(trifluoiOmethyl)-2-pyridyl]oxy]phenyl]’3-methoxy-prop-2-enoate

F

R J

O

To a solution of (E)-2-[2-[(6-chloro-4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy^prop-2enoate (235 mg, 0.606 mmol) in methanol (5 ml) was added palladium on activated carbon (10%) (118 mg, 1.1041 mmol) and ammonium formate (77 mg, 2 equiv., 1.21 mmol). The mixture was heated at 60 *C for 3 h, then cooled to room température, filtered through celite end concentrated under reduced pressure. The residue was partitioned between water and ethyl ecetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried and concentrated. Column chromatography 100% cyclohexane to 40% cyclohexane/ethyl acetate (60.40) gave methyl (E)-2-[2[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate (141 mg. 0.399 mmol, 66% yield).

EXAMPLE 7: methyl (E)-3-methoxv-2-l2-f6-(trifluoromethvl)Dvrimldin-4-vlloxvDhenvllDroo-2-enoate (compound 11 )

To a solution of 4-chloro-6-(trifluoromethyl)pyrimidine (142 mg 0.78 mmol) ln DMF (2 ml) at room température was added methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (162 mg, 0.78 mmol; prepared as described ln Example 3 of EP 0242081 A) and KzCOa (215 mg 1.5561 mmol). The mixture was stirred at room température for 48 h. The mixture was partitioned between diethyl ether and water. The aqueous layer was extracted with ether (x2). The combined organic layers were washed with water and brine, dried with MgSO₄, filtered and concentrated under reduced pressure. Column chromatography cyclohexane 100% to Cyclohexane-ethyl acetate (80:20) followed by a second column with dichloromethane to dichloromethane ethyl acetate (90:10) gave methyl (E)-3methoxy-2-[2-[6-(trifluoromethyl)pyrimidin-4-yl]oxyphenyl]prop-2-enoate (74.6 mg, 0.211 mmol, 27% Yield).

EXAMPLE 8: Methvl (E)-3-methoxv-2-r2-f5-(trifluoromethv0thiazol-2-vlloxvDhenvflDroD-2-enoate (compound 13)

Step 1:2-Bromo-5-(trifluoromethyl)thiazole

Br

To a stirred and degassed solution of 5-(trifluoromethyl)thlazol-2-amine (590 mg, 3 8 mmol) in CH2CI2 (5 ml), Cu(ll)Br (867 mg, 3.88 mmol) and isoamyl nitrite (1.55 ml, 11.64 mmol) were added under argon atmosphère and stirred at room température for 1 h. The reaction was monitored by TLC. After completion of the reaction the mixture was quenched with ice water and extracted with pentane. The organic phase was washed with water and brine, dried over sodium sulphate, filtered and concentrated to give the crude compound. The crude compound was then purified by column chromatography using pentane as an eluent to give 2-bromo-5-(trifluoro-methyl)thlazole (-600 mg, 67% yield).

Step 2:2-(2-lodophenoxy)-5-(trifluoromethyl)thiazole

To a stirred solution of 2-bromo-5-(trifluoro-methyi)thiazole (1.0 g, 4.2 mmol) and 2-Iodophenol (1.0 g, 4.62 mmol) in NMP (10 ml) was added CS2CO3 (2.05 g, 6.3 mmol) at room température and the reaction mixture was stirred for 4 h. The reaction was monitored by TLC. After completion of the reaction the mixture was quenched with ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, brine, dried over sodium sulphate, filtered and concentrated to give a crude product. The crude product was purified by column chromatography to give 2-(2-Iodophenoxy)5-(trifluoromethyl)thIazole (770 mg, 2.07 mmol, 49% yield).

Step 3: Methyl (Z)-2-iodo-3-methoxy-prop-2-enoate

To a stirred solution of methyl (E)-3-methoxyprop-2-enoate (10.0 g, 86.2 mmol) ln CH2CI2 (170 ml), NIS (23.27 g, 103.4 mmol) and AcOH (10.34 g, 172.41 mmol) were added at 0 *C. The reaction mixture was stirred at room temperaturefor 24 h. Then triethylamine (26.17 g, 258.6 mmol) was added and the resulting mixture was stirred for another 12 h at room température. The reaction mixture was then partitioned between CH2CI2 (200 ml) and water (200 ml) and the aqueous layer was extracted with CH2CI2. The combined organic layers were washed with saturated NaCI solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by column chromatography on silica gel using 10 % ethyl acetate - hexane as eluent to afford methyl (Z)-2-lodo-3-methoxy-prop-2enoate (11.0 g, 45.5 mmol, 53 % yield).

Step 4: Methyl (E)-3-methoxy’2-[2-[5-(trifluoromethyi)thiazol-2-yi]oxyphenyl]prop-2-enoate

A) To a stirred suspension of Zn/Ag (1.35 g) In THF (7 mi), TMSCl (0.11 ml) was added at room température and the mixture was stirred at room température for 30 minutes. A degassed solution of

TMEDA (0.96 g, 8.2 mmoi) and methyl (Z)-2’iodo-3-methoxy-prop-2-enoate ( 2.0 g. 8.2 mmol) ln THF (3 ml) was added and the resulting mixture was stirred at room température for 7 h. THF solution was directly used for the cross-coupilng reaction.

B) To a stirred solution of 2-(2-îodophenoxy)-5-(trifluoromethyl)thlazole (400 mg, 1.07 mmol) ln THF (3 ml) which was degassed with argon, Pd(PPh3)< (62 mg, 0.054 mmol) and the Zink reagent ln THF (7 ml) were added. The reaction mixture was stirred at 65*C for 16 h. After completion ofthe reaction, the mixture was cooled to room température and quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate, washed with brine, dried over sodium sulphate, filtered and concentrated to give the crude compound. The crude compound was purified by column chromatography using ethyl acetate-hexane (10-12 %) to give methyl (E)-3-methoxy-2-[2-[5(trifluoromethyl)thiazoi-2-yl]oxyphenyf]prop-2-enoate (240 mg, 0.67 mmol 63 % yield).

EXAMPLE 9: Methvl (E)-3-methoxv-2-f2-fî3-(trifluoromethvl)-2-DvrldvfloxvmethvllDhenvllDroo-2enoate (compound 19)

Step 1: 2-[(2-iodophenyl)methoxy]-3-(trifluoromethyl)pyrfdine

F

To a solution of (2-lodophenyl)methanol (3.5 g. 15 mmol) ln THF (1.7 ml) was added at room température sodium hydride (720 mg, 1.2 equiv., 18 mmol, 60 %). The mixture was stirred at room température for 1 h. Then 2*chloro-3-(trifluoromethyl)pyridlne (3.3 g, 1.2 equiv., 18 mmol) was added and the mixture was heated at reflux for 72 h. The mixture was cooled to room température and water was added. The mixture was extracted three times with ethyl acetate. The combined organic extracts were washed with brine and dried with MgSO< filtered and then concentrated under reduced pressure. Purification by column chromatography with gradient elution 100% cyclohexane to cyclohexane/ethyl acetate (80:20) gave2-[(2-lodophenyl)-methoxy]-3-(trifluoromethyl)pyridine (4.41 g. 11.6 mmol, 78% yield)

Step 2: Methyl (E)-3-methoxy-2-[2-[(3-(trifluoromethyl)-2-pyrfdyl]oxymethyl]phenyl]prop-2-enoate

A) To a suspension of activated zinc dust (1.35 g, 20.1 mmol) in THF (4 ml) was added chlorotrimethylsilane (100 pl, 0.772 mmoi). The mixture was stirred for 20 min before the addition of a solution of methyl (Z)-2-lodo-3-methoxy-prop-2-enoate (2 g, 8.26 mmol) and Ν,Ν,Ν',Ν’tetramethylethane-1,2-diamine (1.24 mL, 8.2 mmol) dropwise. The mixture was stirred for 3 h and

-45then allowed to settle. The solution of iodo-[(Z)-2-methoxy- 1-methoxycarbonyi-vinylJzinc; Ν,Ν,Ν',Ν’tetramethylethane-1,2-diamine was used ln the next step.

B) lodo-[(Z)-2-methoxy-1-methoxycarbonyLvinyl]zînc; N,N,N',N*-tetramethylethane-1,2-diamine (8.2 mmol, 8.2 mmoi) was added to a solution of 2-[(2-iodophenyl)methoxy]-3-(trifluoromethyl)pyridine (2.2 5 g, 5.8 mmol) and Pd(PPhs)4 (50 mg, 0.05 equiv., 0.29 mmoi) ln THF (5 mi). The mixture was heated to 65 ’C for 4 h. The mixture was quenched by addition of saturated aqueous NHiCI solution. The mixture was extracted with ethyl acetate. The organic layer washed with brine, dried with MgSO< filtered and concentrated under reduced pressure. Column chromatography 100% cyclohexane to cyclohexane/ethyl acetate (60:40) gave methyl (E)-3-methoxy-2-[2-[[3-(trifluoromethy1)-210 pyridyl]oxymethyl]phenyl]prop-2-enoate (1.24 g, 3.38 mmol, 58% yield).

EXAMPLE 10: Methyl (E)-3-methoxv-2-f2-n3-(trifluoromethvnDvrazin-2-vl1oxvmethvnphenvllDror>-2enoate (compound 20)

F

To a suspension of 3-(trifluoromethyl)pyrazin-2-ol (100 mg, 0.609 mmol) ln benzene (5 ml, 55.4 mmol) was added AgîCCh (203 mg, 1.2 equiv., 0.731 mmol) and methyl (E)-2-[2-(bromomethyl)phenyl]-3-methoxy-prop-2-enoate (174 mg, 0.609 mmol; prepared as ln J. Agric. Food. Chem, 2007, 55, 5697-5700). The mixture was heated at 80 *C for 72 h. The mixture was cooled to room 20 température, diluted with dichloromethane, fiitered and concentrated. The material was purified by column chromatography cyclohexane 100% to cyclohexane/ethyl acetate (60:40) followed by reversed phase chromatography (27 mg, 0.073 mmol, 12% yield).

Table 3 & 4 below lists the compounds of the invention 1 to 23 and comparative compounds respectively.

The table 3 & 4 contains literature référencés for known compounds and/or physical state or melting point and/or 1H-NMR data. The following abbrevlations are used: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, m p.= melting point, ppm = parts per million.

-46Table3: methoxyacrylate compounds: compounds 1 to 23 (ofthe Invention)

1H-NMR [ppm]	i * m — X 3 ''t • <fl «n. m — x o n X ΗΊ 1/1 nIÜ» t* b* m m H . A « [Y x IN —· in JS . IN IN . x q in 42. f*> *** — oo 4Îx Ξ co m . 2 4Η= • · <n 2 *· -5 « Π c £ T ~ Ξ m r* in	In CDCh: 1.41 (s, 9H), 3.67 (s, 3H), 3.83 (s, 1H), 7.27-7.35 (m, 2H), 7.38-7.43 (m, 1H), 7.56-7.60 (m, 1H), 7.61 (s, 1H)
W* •_ d É	76-78	E 3 00
	oZ Q>o ) OZ O \ \ o /	οί O o x 1 P X
Literature référencés/ CAS	WO 9518789 Table 1, compound No. 1.24 171276-46- 3	WO 9505368 Table 1, compound No. 8 163619-68- 9
Compound no.	^4	N

3.64 (s, 3H), 3.77 (s, 3H), 7.29-7.35 (m, 3H), 7.35-7.48 (m, 1H), 7.54 (s, 1H)	W? O r* . ΠΊ X m JÎ «f co S ni X RJ E <Λ ” ID θ m < % θ' — <SI o — c x £ m
LO 7 LÛ	64-66
X o o X X U.	o o i/ X Ÿ*'
GB 2193495A Table 1, compound No. 115 115314-10- 8	WO 9505368 Table 5, compound No. 8 163619-690
10	r*

ln CDCI3: 3.55 (s, 3H), 3.70 (s, 3H), 6.99 (d, 1H),7.14 (d, 1H), 7.18 (d, 1H), 7.23-7.28 (m, 1H), 7.31-7.40 (m, 2H), 7.42 (s, 1H), 8.32 (d, 1H)	ln CDCh: 1.32 (s, 9H), 3.62 (s, 3H), 3.77 (s, 3H), 6.83 (s, 1H), 7.1-7.5 (m, 4H), 7.52 (s, 1H), 8.79 (s, 1H).
78-80	E 5 bû
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EP 242081 Table 1, compound No. 11 114077-75- 7
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Table 4: methoxyacrylate compounds: comparative compounds A to AD

1H-NMR [ppm]
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Literature refei		I CSAA383699	EP 382375 131860-33-8 Azoxystrobin		WO 9521153	171276-50-9
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-66BIOLOGY EXAMPLES·

Example B1: Aedes aeavotl (Yellow fever mosquito)

The individual wells of a tweive (12) weil tissue culture plates were treated with 100 pl of an éthanol solution containing a test compound at 20 ppm concentration. Once the deposlts were dry, five non5 blood fed adult female Aedes eegypti (beween two to five days old) were added to each well, and sustalned with a 10% sucrose solution in a cotton wool plug. Assessment ofthe knockdown after 1 hour, and mortality after 48 hours was carried out.

ln case of multiple tests, the mean value is reported. Results for the compounds of the invention 10 and comparative compounds are shown in Table B1.

Example B2: Anopheles stephensl (Indlan malaria mosquito)

The individual wells of a tweive (12) well tissue culture plates were treated with 100 pi of an éthanol solution containing a test compound at 20 ppm concentration. Once the deposits were dry, five non15 blood fed adult female Anopheles stephensl (beween two to five days old) were added to each well, and sustalned with a 10% sucrose solution in a cotton wooi plug. Assessment ofthe knockdown after 1 hour, and mortality after 48 hours was carried out.

in case of multiple tests, the mean value Is reported. Results for the compounds of the invention 20 and comparative compounds are shown in Table B2.

Example B3~ Aedes aegyptl or Anopheles stephensl

The Individual wells of six (6) well tissue culture plates were treated with 250 μΙ of an éthanol solution containing a test compound at a defined concentration. Once the deposits were dry, ten 25 non-blood fed adult female Aedes aegyptl or Anopheles stephensl (each between two to five day old) were added to each well, and sustalned with a 10% sucrose solution in a cotton wooi plug. Assessment of the mortality was carried out at 48 hours.

Each treatment was replicated twice, with the mean mortality recorded. .

Results for certain compounds ofthe invention and comparative compounds are shown in Table B3.

Example B4· Cross résistance studies:

The Individual weiis of six (8) well tissue culture plates were treated with 250 μΙ of an éthanol solution containing a test compound at a defined concentrations. Once the deposits were dry, ten non-blood fed adult female mosqultoes from strains with characterised Insecticide résistance mechanisms were added to each well, and sustained with a 10% sucrose solution ln a cotton wool plug, ln each study, a set of plates were infested with a known Insecticide susceptible strain of mosqultoes from the same généra as the résistant strains.

-67Assessment of the knockdown after 60 minutes and mortality after 24 hours was carried out. Each treatment was replicated a minimum of four times, with the mean knockdown or mortality recorded.

A comparison ofthe knockdown and mortalityofthe résistant strain of mosquitoes was madeto that 5 of the susceptible to identify evidence of cross résistance. Results are shown in Table B4.

Example B5· Bottle based cross résistance study:

Based on the CDC bottle assay” (described at http://www.cdc.gov/malaria/resources/pdf/fsp/ir_manual/ir_cdc_bioassay_en.pdf) 1ml of éthanol containing a test compound at a defined concentration was added to a 250 ml glass bottle and the bottles were placed on a rolling table to coat the Inner surfaces as the solvent evaporated. Once dry, twenty five non-biood fed adult female mosquitoes ofthe appropriate species and straîns (each three day ofd} were aspirated from the stock culture and gently blown into the exposure bottles. The lid ofthe bottle was replaced and the bottle placed upright out of direct sun light under standard culture conditions, nominally 28C and 60 - 80% relative humidity.

A stopwatch was started, and the assessment of the knock-down were made after 15 minutes and 60 minutes. A mosquito was said to be knocked down if It was unable to stand, following the CDC définition. The bottles were replaced In an upright position when not being assessed.

After one hour the mosquitoes were carefully removed from the bottle with an asplrator and placed in a recovery cup. The mosquitoes were supplied with a 10% sucrose solution on a cotton wool bung, and stored under culture conditions. Assessments of the mortality were made after 24 hours.

Each treatment was replicated a minimum of four times, with the mean knockdown or mortality recorded. In each study, a set of bottles was Infested with a known Insecticide susceptible strain of mosquitoes from the same généra as the résistant straîns. Results are shown in Tables B5.

Example B6~ Evaluation of residual insecticldal formulations .

Experimental surfaces were sprayed with diluted residual insecticide formulation comprising a compound of the Invention using an automated hydraulic sprayer fitted with an 8003 fiat fan nozzle corresponding to a coverage of 500mg of compound per m2. Also applied was a lambda-cyhalothrin formulation (DEMAND 10 CS) such that there was 25mg of lambda-cyhalothrin Al per m2. The pirimiphos-methyl formulation (ACETELLIC 300CS) was applied so that there was 1000mg of pirimiphos-methyl Al per m2 (Table B6b).

The treated surfaces were stored In a controlled environment room at 28*C, ambient humidity and under low light conditions for 1 (one) week.

-68Three to five day oid non-blood fed adult mosquitoes were taken from the culture and lightly anaesthetised with carbon dioxide. Ten females were selected and placed in a 250ml plastic cup, retained with a net lld, provided with a 10% sucrose solution soaked in a cotton wool bung and heid under cul turing environmental conditions.

After twenty four hours, treated tiles. treated 7 days previously with a formulation, were removed from storage. A cup of the pre-selected mosquitoes were again llghtiy anaesthetised with carbon dioxide and transferred from the holding cup to the base of a 9cm plastic Pétri dish. The treated side ofthe relevant surface was placed over the Pétri dish and held in piace with an elastic band. Once the mosquitoes had recovered from the anaesthetic, ca. 1 minute, the treated surface attached to the Pétri dish was placed on a holding rack, such that treated side was at an angle of 60’ to the horizontal.

After one hour an assessment of mosqulto knockdown was made. A mosqulto was said to be knocked down If it was unable to right itself once it had fallen over. The mosquitoes were lightly anaesthetised again, and removed from the Pétri dish exposure chamber and retumed to the holding cups. The mosquitoes were supplied with a 10% sucrose solution soaked in a cotton wool bung and held under culturlng environmental conditions. An assessment of mortality was made 24 hours after exposure. A mosqulto was said to be dead If it is unable to right itself once it has fallen over. Results are shown in Tables B6.

Example B7: Evaluation of insecticide Impreonated polymer surfaces

Préparation of polymeric sheets: Certain methoxyacrylate were Impregnated Into three polymère: LDPE (low density polyethylene), HDPE (high density polyethylene) and PP (polypropylene) in different concentrations by mixing the respective polymer with a compound at high températures and the résultant polymeric material were then mould into thin dises or plaques.

Twenty four hours prior to the relevant assessment intervals, three to five day old non-blood fed adult mosquitoes were taken from the culture and lightly anaesthetised with carbon dioxide. Ten females were selected and piaced in a 250ml plastic cup, retained with a net lld, provided with a 10% sucrose solution soaked ln a cotton wool bung and held under culturing environmental conditions.

After twenty four hours, Impregnated polymer sheets (measuring about 150mm in diameter and about 0.1 mm in thickness) were removed from storage and wrapped around the giazed side of an

11cm ceramlc tile and held in placewith an elastic band. The âge ofthe polymersheets used are indicated in the tables below. A cup of the pre-seiected mosquitoes were again lightly anaesthetised with carbon dioxide and transferred from the holding cup to the base of a 9cm plastic

Pétri dish. The relevant Impregnated polymer sheet was placed over the Pétri dish end held ln place with an elastic band. Once the mosquitoes had recovered from the anaesthetic, ca. 1 minute, the

-69Impregnated polymer sheet was placed on a holding rack, such that treated side was at an angie of 60° to the horizontal.

After one hour an assessment of mosquito knockdown was made. A mosquito was said to be knocked down If It was unable to right itself once It had fa iien over. The mosqultoes were tightly anaesthetised again, and removed from the Pétri dish exposure chamber and retumed to the holding cups. The mosquitoes were supplied with a 10% sucrose solution soaked In a cotton wool bung and held under culturing environmental conditions. An assessment of mortality was made 24 hours after exposure. A mosquito was said to be dead If it is unable to right Itseif once it had fallen 10 over. Results are shown in Tables B7.

-70Table B1;

Compound no.	Knockdown (%)	Mortaîfty (%)
1	50	90
2	0	80
3	0	100
4	100	100
5	100	100
6	100	100
7	100	100
8	67	100
9	0	80
10	80	93
11	100	100
12	100	100
13	100	100
14	0	40
15	50	100
16	0	80
17	100	100
18	0	40
19	20	100
20	100	100
21	50	90
22	100	100
23	100	100
A	0	0
B	0	0
C	0	0
D	0	0
E	0	0
F	0	60
G	0	0
H	0	0
1	0	40
J	0	0
K	0	0
L	0	0
M	0	0
N	0	0
0	0	0
P	0	0
Q	0	0
R	0	0

S	0	0
T	0	0
U	0	0
V	0	0
w	0	0
X	0	0
Y	0	0
Z	0	0
AA	0	0
AB	60	100
AC	0	40
AD	0	0
Blank	0	0
DDT (10 ppm)	35	90
Lambdacyhalothrin (2 pem)	92	100

Table B2:

Compound no.	Knockdown (%)	Mortallty (%)
1	40	100
2	40	100
3	100	100
4	80	100
5	100	100
6	100	100
7	67	100
8	100	100
9	100	100
10	93	100
11	80	100
12	100 ·	100
13	100	100
14	0	100
15	40	100
16	20	100
17	100	100
18	100	100
19	40	100
20	100	100
21	100	100
22	100	100
23	20	100

•72-

A	NT	NT
B	NT	NT
C	NT	NT
D	NT	NT
E	NT	NT
F	60	100
G	NT	NT
H	NT	NT
1	NT	NT
J	NT	NT
K	NT	NT
L	NT	NT
M	NT	NT
N	NT	NT
0	NT	NT
P	NT	NT
Q	NT	NT
R	NT	NT
S	NT	NT
T	NT	NT
U	NT	NT
V	NT	NT
w	NT	NT
X	NT	NT
Y	NT	NT
Z	NT	NT
AA	NT	NT
AB	100	100
AC	100	100
AD	NT	NT
Blank	0	0
DDT (10 ppm)	. 70	80
Lambdacyhalothrin (2 ΕΡΠϋ	83	100

Notes, NT ia nul tested

Table B3:

	Aedes aegyptl	Anopheles stephensl
ppm	5	5
compound

1	74	100
2	90	100
4	78	98
5	85	100
6	66	98
7	78	95
8	100	100
10	47	93
12	43	100
13	78	100
15	70	95
16	20	95
17	5	55
18	70	100
19	75	100
20	70	100
21	85	100
22	100	100
23 .	60	93
F	30	20
AB	75	80
AC	4	75
ppm	5	5
DDT	85	59

ppm	0.2	0.2
Lambda-cyhalothrin	99	84

Table B4:

		Knockd	own (%) |			Morta	iity (%
Compound	4	6	7	10	Permethrin |	1 4	6	7	10	Permethrin
concentratlon/ppm	2.00	2.0	2.50	1.56	2.50 1	| 2.00	2.00	2.50	1.56	2.50
An. Gambiae Klsumu sus	67	86	100	90	100 1	1 95	100	100	100	100
An. Gambiae Klsumu rdl	30	78	90	70	100 1	1 100	89	100	70	100
An. Gambiae Tiassalé	70	84	90	80	5 1	1 100	94	85	75	14
An. Arabiensls Moz SUS	0	90	95	90	75 1	1 95	100	100	90	100
An. Arablensis Ndjamina	100	100	NT	68	NT I	1 100	100	NT	79	NT
Ae. aegyptl Caymon	45	5	52	55	0 1	1 90	63	28	55	45
Ae. Aegyptl New Orléans	75	95	38	70	91 1	1 100	100	100	85	100
An. stephensl	95	100	40	0	85 1	| 100	100	100	100	100

Notes. NT Is not tested

Table B5a:

	Knockdown (%) at 15mlns |	| Knockdown (%) at 60mins |	| Mortality (%)
Compound	4	6	7	10	Permethrin |	1 4	6	7	10	Permethrin |	1 4	6	7	10	Permethrin
concentration/ppm	20	20	20	20	20 |	1 20	20	20	20	20 1	1 20	20	20	20	20
An. Gambiae Kisumu sus	48	100	100	71	100 1	I 100	100	100	100	100 1	I 100	100	99	48	100
An. Gambiae Tiassalé	17	93	70	9	0	1 96	98	97	24	99 1	r	91	95	5	85
An. stephensi	10	83	37	57	97 |	| 100	100	100	100	100 |	1 80	100	100	30	100

Table B5b:

	Mortality (%)
Compound	8	13	22	Permethrin
concentration/ppm	25	25	25	25
FUMOZ	56	70	68	24
VK7	20	61	96	3
Kisumu sus	61	94	100	99

Table B5c:

	Mortality (%)
Compound	7	Permethrin
concentration/ppm	25	25
FUMOZ	20	46
VK7	19	4

Kisumu sus

97

100

Notes on mosquito species used in tables B4 & B5:

Name	Species	Country ofOrigin	Phenotype
Kisumu	Anopheles gambiae	Kenya	Susceptible
Kisumu Rdl	Anopheles gambiae	Kenya	Dieldrin résistant
Tiassalé	Anopheles gambiae	Cote d'ivoire	Pyrethroid résistant
Moz	Anopheles arabîensis	Mozambique	Susceptible
New Orléans	Aedes aegyptl	USA	Susceptible
Cayman	Aedes aegypti	Grand Cayman	Pyrethroid, carbamate & DDT résistant
Ndjamina	Anopheles arabiensis	Chad	Pyrethroid résistant
VK7	Anopheles coluzzii	Burkina Faso	Pyrethroid résistant
FUMOZ	Anopheles funestus	Mozambique	Pyrethroid résistant
SYN	Anopheles stephensi	India	Susceptible

-77Table B6a:

formulation	compound	Knockdown (%)	Mortallty (%)
4A	4	70	100
7A	7	77	100
10A	10	3	30
Demand 10CS	Lambda-cyhalothrin	100	100
Water	control	0	0

Notes: Formulations 4A, 7A and 10A are each aqueous suspension concentrâtes containing about 10wt%of active Ingrédient and also contalnlngfng conventional co-formulants ln standard amounts, such as a dispersant, antifreeze, preservattve, thickener, wetter, emuisler. and water as the carrier,

Table B6b:

formulation	compound	Knockdown (%)	Mortallty (%)
7B	7	67	100
ACTELLIC 300CS	pirimiphos-methyl	0	100
Water	control	0	3

Notes Formulations 7B Is an aqueous suspension concentrâtes containing about 10 wt% of active Ingrédient and also corrtalnlnglng conventional co-formulants In standard amounts, such as a dispersant antifreeze. preservattve. thickener, wetter, emuisler, and water as the carrier.

Table B7a: âge of Impregnated polymer 4 to 6 weeks old against Aedes aegyptl (knockdown)

		knock-down (%)
compound	Al content, wt%	LDPE	HDPE	PP
4	2	63	53	63
6	2	100	87	83
7	2	100	83	67
10	2	23	80	0
17	2	100	NT	NT
Permethrin	2	100	100	87
Blank	n/a	0	0	0

Table B7b: âge of Impregnated polymer 4 to 6 weeks old against Aedes aegyptl (mortallty)

		mortallty (%)
compound	Al content, wt%	LDPE	HDPE	PP
6	2	90	17	13
7	2	97	47	23
10	2	97	17	13
Permethrin	2	100	97	80

*78-

Blank

n/a

0

0

0

Table B7c: âge of impregnated polymer 4 to 6 weeks old against Anopheles Stephens! (knockdown)

		knock-down (%)
compound	Al content, wt%	LDPE	HDPE	PP
4	2	87	93	100
6	2	97	87	100
7	2	100	93	93
10	2	87	90	0
Permethrln	2	100	100	100
Blank	n/a	0	0	0

Table B7d: âge of impregnated polymer 4 to 6 weeks old against Anopheles Stephens/(mortality)

		mortality (%)
compound	Al content, wt%	LDPE	HDPE	PP
4	2	70	60	87
6	2	83	60	57
7	2	97	87	87
10	2	93	73	10
Permethrln	2	100	70	23
Blank	n/a	0	0	0

Table B7e: âge of impregnated polymer 6 to 8 weeks old against Anopheles stephensl (knockdown)

		knock-down (%)
compound	Al content, wt%	LDPE	HDPE	PP
4	2	70	77	90
6	2	100	100	90
7	2	87	100	100
10	2	90	20	17
Permethrln	2	100	100	100
Blank	n/a	0	0	0

Table B7f: âge of Impregnated polymer 6 to 8 weeks old against Anopheles stephensl (mortality)

		mortality (%)
compound	Al content, wt%	LDPE	HDPE	PP

4	2	100	80	100
6	2	77	63	80
7	2	100	87	77
10	2	100	17	93
Permethrln	2	100	97	67
Blank	n/a	10	7	13

Table B7g: âge of Impregnated polymer 2 to 4 weeks old against Aedes aegypti (knockdown)

		knock-down (%)
compound	Al content, wt%	LD PE	HDPE	PP
5	2	13	33	80
8	2	100	100	n/t
12	2	100	97	100
13	2	100	100	100
22	2	100	93	100
Blank	n/a	0	0	0

Table B7h: âge of Impregnated polymer 2 to 4 weeks old against Aedes aegypti (mortality)

		mortality (%)
compound	Al content, wt%	LDPE	HDPE	PP
5	2	13	27	40
8	2	100	53	n/t
12	2	100	27	80
13	2	93	73	87
22	2	100	93	100
Blank	n/a	0	7	13

Table B7I: âge of Impregnated polymer 6 to 8 weeks old against Aedes aegypti (knockdown)

		knock-down (%)
compound	Al content, wt%	LDPE	HDPE	PP
5	2	85	60	70
8	2	100	100	n/t
12	2	95	100	100
13	2	100	100	100
22	2	100	95	100
Blank	n/a	0	0	0

Table B7J* âge of impregnated polymer 6 to 8 weeks old against Aedes aegypti (mortality)

		mortality (%)
compound	Al content, wt%	LDPE	HDPE	PP
5	2	95	15	55
8	2	100	75	n/t
12	2	55	75	70
13	2	95	65	35
22	2	100	100	100
Blank	n/a	0	10	5

Table B7k: âge of impregnated polymer 2 to 4 weeks old against Anopheles stephensii (knockdown)

		knock-down (%)
compound	Al content, wt%	LDPE	HDPE	PP
5	2	80	100	90
8	2	100	100	n/t
12	2	100	100	100
13	2	100	100	100
22	2	100	100	100
Blank	n/a	7	0	0

Table B7I: âge of impregnated polymer 2 to 4 weeks old against Anopheles stephensii (mortality)

		mortality (%)
compound	Al content, wt%	LDPE	HDPE	PP
5	2	87	80	67
8	2	100	100	n/t
12	2	100	97	97
13	2	100	100	100
22	2	93	97	93
Blank	n/a	3	10	0

Table B7m: âge of impregnated polymer 8 to 12 weeks old against Anopheies stephensii (knockdown)

		knock-down (%)
compound	Al content, wt%	LDPE	HDPE	PP
5	2	70	50	20
8	2	90	100	n/t
12	2	30	100	100
13	2	100	90	100
22	2	80	90	100

Blank

n/a

0

0

0

Table B7n: âge of Impregnated polymer 8 to 12 weeks old against Anophefes stephensil (mortality)

		mortality (%)
compound	Al content, wt%	LD PE	HDPE	PP
5	2	100	20	50
8	2	100	80	n/t
12	2	0	30	70
13	2	80	0	10
22	2	100	90	100
Blank	n/a	0	0	0

Claims (16)

1. Use of one or more methoxyacrylate compounds selected from Table 1 below in mosquito control.

Table 1

19 Μ. 0 (XIX) 20 F RÏ F ίΎ^Οχ/χ ΑΑα ° (XX) 21 F ^ρζΧΧρ |f 0 (XXI) 22 οΛ-θ-Jp. 1 0 JLn. 0 /SZVx 0 (XXII) 23 f ήχΛ _FAy^N /-^ογΑ^-^ο\ F 0 (XXIII)

2. The use according to claim 1 wherein the methoxyacrylate compound is selected from compound 4,6, 7,8,10 and 13.

3. The use according to either claim 1 or 2 wherein the development of vector-bome diseases Is reduced by the mosquito control defined in claim 1.

4. An Integrated mosquito vector control product comprising one or more methoxyacrylate compounds defined in either claim 1 or 2.

5. The vector control product according to claim 4 wherein the solution îs a net incorporated with one or more methoxyacrylate compounds defined in either claim 1 or 2.

6. The vector control product according to claim 4, wherein the solution îs a composition for coating a net, which composition comprises one or more methoxyacrylate compounds defined in either claim 1 or 2.

7. The vector control product according to claim 4, wherein the solution is a composition for spraying surfaces of a dwelling, which composition comprises one or more methoxyacrylate compounds as defined in either claim 1 or 2.

8. The vector control product according to any one of claims 4 to 7, wherein a further insecticide and/or synergist is présent.

9. A polymeric material incorporated with a compound defined in either claim 1 or 2. which material Is useful for making substrate or non-living material, such as threads, fibres, yams, pellets, nets and weaves.

10. A method of controlling mosquitoes, preferably mosquito vectors of pathogenîc disease, with one or more compounds defined in either claim 1 or 2.

11. A kit for treating a fibre, yam, net and weave by coating wash résistant Insectlcldal properties thereto comprising: a first sachet comprising a pre-measured amount of at least one compound defined in either claim 1 or 2, and a second sachet comprising a pre-measured amount of at least one polymeric binder.

12. A method for treating a fibre, yarn, net and weave by coating wash résistant Insectlcldal properties thereto comprising (i) preparing a treatment composition, which comprises at least

-88one compound defined ln either claim 1 or 2, (ii) treating said fibre, yam, net and weave and (iii) drying the resulting treated fibre, yam, net and weave.

13. A method of preparing a polymeric material impregnated with a compound defined in either claim 1 or 2, which material is useful for making substrate or non-living material, such as threads, fibres, yarns, peilets, nets and weaves, which method comprises mixing a polymer with a compound defined in either claim 1 or 2 at a température between 120 to 250 °C.

14. A method for mosquito vector-control, ln particular controlling mosquito vectors carrying pathogenic disease, which method comprises (a) applyïng an effective amount of a liquid composition comprising a compound defined in either claim 1 or 2, and a polymeric binder, and optionally, one or more other insecticides, and/or synergists, to a surface of a dweliing; and/or (b) placing a substrate or non-living material incorporated with a compound defined in either claim 1 or 2, and optionally an additive, one or more other insecticides, and/or synergists, within a dweliing.

15. A net incorporated with a compound defined in either claim 1 or 2 having a biological activity in accordance with the WHOPES guldelines of a knockdown after 60 minutes of between 95 percent and 100 percent and/or a mortaiity after 24 hours of between 80 percent and 100 percent after 20 washes.

16. A methoxyacrylate compound listed as compound 3, 5,9,11,13,14,16,17,19,20,21 and 23 in Table 1 as defined in claim 1.