EA043836B1 - NAPHTHALENEISOXAZOLINE COMPOUNDS FOR THE CONTROL OF INVERTEBRATE PESTS - Google Patents

Description

Field of technology to which the invention relates

This invention relates to specific isoxazoline compounds and compositions that can be used for agricultural and non-agricultural purposes, and methods of using them to control invertebrate pests, such as arthropods, in both agricultural and non-agricultural environments.

State of the art

The control of invertebrate pests is an extremely important task, the solution of which makes it possible to achieve high crop yields. Damage caused by invertebrate pests to agricultural crops during their cultivation and storage can lead to a significant decrease in the efficiency of agricultural production and, as a result, to increased costs for the consumer. In addition, it is also important to control invertebrate pests in forestry, when growing greenhouse crops, ornamental plants, when growing plants in nurseries, when storing food and dietary fiber products, in the household, when caring for lawns, for the preservation of timber and for people's health. The industry produces many products for these purposes, but there is still a need for new compounds that are more effective, cheaper, less toxic, environmentally friendly, or have different sites of action.

The essence of the invention

This invention relates to the compounds of formula 1, compositions containing them and their use for the control of invertebrate pests

where J represents C2- _C4 alkyl substituted with one cyano group or cyclopropyl; or

J represents

J-2 J-3

J-4 J-5 J-6

R ^1a is Cl or CF3;

R ^1b represents H or Cl;

R ² represents C ₁ -C ₄ alkyl, unsubstituted or substituted with substituents selected from cyano, nitro and OR ⁹ ;

R ³ represents H or C ₁ -C ₄ alkyl, unsubstituted or substituted with substituents selected from cyano, nitro and OR ⁹ ;

R ⁴ represents H or C ₁ -C ₄ alkyl;

R ⁵ represents H or C ₁ -C ₄ alkyl;

R ⁶ represents H or C ₁ -C ₄ alkyl;

R ⁷ represents H, C ₁ -C ₄ alkyl or C ₁ -C ₄ haloalkyl;

X represents -O- or -C(O)-;

R ⁸ represents H, C ₁ -C ₄ alkyl or C ₁ -C ₄ haloalkyl;

R ⁹ represents H or C ₁ -C ₄ alkyl;

R ¹⁴ represents H or C ₁ -C ₄ alkyl, unsubstituted or substituted with substituents selected from cyano, nitro and OR ⁹ ;

R ¹⁵ represents H or CrC ₄ alkyl;

R ¹⁶ represents C ₁ -C ₄ alkyl or C ₁ -C ₄ haloalkyl;

Q represents pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyloxazolyl, thiazolyl, isoxazolyl , isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl or 1,3,4-thiadiazolyl , each of which is unsubstituted or substituted with substituents independently selected from cyano, nitro, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkylthio, C ₁ -C ₄ haloalkylthio, C 1 -C ₄ alkylsulfinyl, C ₁ -C ₄ haloalkylsulfinyl, C ₁ -C ₄ alkylsulfonyl, C _{1 -C 4} haloalkylsulfonyl, C ₂ -C ₅ alkoxycarbonyl, C ₂ -C ₅ alkylaminocarbonyl and C ₃ -C ₅ dialkylaminocarbonyl.

The present invention further provides a composition comprising a compound of formula 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. In one embodiment, the present invention also provides a composition for controlling an invertebrate pest, comprising a compound of formula 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, wherein said composition is optionally additional includes at least one additional biologically active compound or agent.

The present invention provides a method for controlling an invertebrate pest, comprising contacting the invertebrate pest or its habitat with a biologically effective amount of a compound of formula 1 (eg, in the form of a composition described herein). In addition, the present invention also relates to such a method wherein an invertebrate pest or its habitat is contacted with a composition comprising a biologically effective amount of a compound of formula 1 and at least one additional component selected from the group consisting of surfactants, solids thinners and liquid thinners.

The present invention also provides a method of protecting seeds from an invertebrate pest, comprising contacting the seeds with a biologically effective amount of a compound of Formula 1 (eg, in the form of a composition described herein). The present invention also relates to treated seeds.

The present invention also provides a method of increasing the vigor of a crop, comprising contacting the crop, seeds from which the crop is grown, or a location (e.g., growing medium) of the crop with a biologically effective amount of a compound of Formula 1 (e.g., in the form described herein compositions).

Detailed Description of the Invention

As used herein, the terms constitute, constitute, include, include, have, having, contains, containing, characterized, or any other variation thereof are intended to denote a non-exhaustive inclusion, subject to any expressly stated limitation. For example, a composition, mixture, process or method that includes a list of elements is not necessarily limited to those elements, but may include other elements that are not expressly listed or inherent in such composition, mixture, process or method.

The transition phrase consisting of excludes any unspecified element, step, or ingredient. If this phrase is used in a claim, such claim will be closed to include materials not listed therein, except impurities that typically accompany the materials listed in the claim. In the case where the phrase consisting of is present in the sentence of the body of the claim, and not immediately after the preamble, then this phrase imposes a limitation only on the element specified in that sentence; other elements are not generally excluded from this claim.

The transitional phrase consisting essentially of is used to define a composition or method that includes materials, steps, features, components or elements other than those expressly described, provided that these additional materials, steps, features, components or elements are not substantially affect the main and new characteristic(s) of the claimed invention. The term consisting mainly of occupies an intermediate meaning between consisting and consisting of.

Where the inventors have defined the invention or part thereof by a non-limiting term such as comprising, it will be understood (unless otherwise stated) that it is intended that in describing such invention the terms consisting essentially of or consisting of .

Also, unless explicitly stated otherwise, or refers to an inclusive or, not an exclusive or. For example, condition A or B is satisfied by any of the following conditions: A

- 2 043836 is true (or present) and B is false (or absent), A is false (or absent) and B is true (or present), and both A and B are true (or present).

It is further intended that the singular form for an element or component of the invention is non-limiting as to the number of examples (ie, presence) of the element or component. Therefore, it should be understood that a singular form indicating one or at least one element or component also includes a plurality of elements or components, unless the singular form clearly designates one element or component.

As used herein, the term invertebrate pest includes arthropods, gastropods, nematodes and helminths as agricultural pests. The term arthropod includes insects, mites, spiders, scorpions, millipedes, bipeds, woodlice, and sessile bellies. The term gastropod includes snails, gastropods, and other stalked animals. The term nematodes includes members of the nemotoda phylum.

As used herein, control of an invertebrate pest means inhibition of the development of an invertebrate pest (including mortality, food reduction, and/or male confusion), and related expressions are defined similarly.

The term agricultural refers to the production of field crops, for example for use as food or fiber, and it includes the growing of corn or wheat, soybeans and other legumes, rice, grain crops (such as wheat, oats, barley, rye and rice), leafy vegetables (e.g. lettuce, cabbage, and other brassicas), fruiting vegetables (e.g. tomatoes, peppers, eggplant, cruciferous and squash), potatoes, sweet potatoes, grapes, cotton, fruit trees (e.g. apples, stone fruits and citrus ), bush fruiting plants (such as berries and cherries) and other specialty crops (such as canola, sunflowers and olives).

The term non-farm refers to crops that are not field crops, such as horticultural crops (for example, greenhouse plants, seedlings or ornamental plants not grown in the field), residential, agricultural, commercial and industrial structures, lawns (for example, turf growing , pasture, golf course, lawn, sports field, etc.), timber, food storage, agroforestry and vegetation control, as well as public health applications.

The term crop development capacity refers to the rate of growth or biomass accumulation of a crop. Increased vigor refers to the increase in growth or biomass accumulation of a crop compared to a control crop that has not been treated. The term yield refers to the output of grown agricultural material, both in terms of quantity and quality, obtained after harvesting an agricultural crop. Yield increase refers to the increase in yield compared to a control crop that was not treated.

The term biologically effective amount refers to an amount of a biologically active compound (e.g., a compound of Formula 1) sufficient to achieve the desired biological effect when applied to (i.e., upon contact with) the invertebrate pest being controlled or its habitat, or on the plant, the seeds from which the plant is grown, or the location of the plant (eg, growing medium) to protect the plant from damage by an invertebrate pest or to achieve another desired effect (eg, increasing the vigor of the plant).

In the above enumerations, the term alkyl, used either alone or in compounds such as alkylthio or haloalkyl, includes linear or branched alkyl such as methyl, ethyl, n-propyl, isopropyl, and various isomers of butyl, pentyl or hexyl.

Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and various isomers of butoxy, pentoxy and hexyloxy. Alkylthio includes branched and linear alkylthio moieties such as methylthio, ethylthio, and various isomers of propylthio, butylthio, pentylthio, and hexylthio.

The term halogen, either alone or in compound words such as haloalkyl, or when used in descriptions such as alkyl substituted with halogen, includes fluorine, chlorine, bromine or iodine. In addition, when used in compound words such as haloalkyl, or when used in descriptions such as alkyl substituted with halogen, said alkyl may be partially or completely substituted with halogen atoms, which may be the same or different. Examples of haloalkyl or alkyl substituted with halogen include F3C-, επί-, CF3CH2- and CF3CQ2-.

The chemical designations S(O) and S(=O) used in the invention represent the sulfinyl moiety. The chemical designations SO2, S(O) ₂ and S(=O) ₂ used in the invention represent the sulfonyl moiety. The chemical designations C(O) and C(=O) used in the invention represent the carbonyl moiety. The chemical designations CO2, C(O)O and C(=O)O used in the invention represent the oxycarbonyl moiety.

The dotted line in a fragment of the structure indicates the point of attachment of the fragment to the rest of the molecule. For example, when the variable J in Formula 1 is defined as J-1, the dotted line in

- 3 043836 structure J-1 means that J-1 is attached to the remainder of the structure of formula 1 in the position as shown below.

The X variable in J-4 is defined as -O- or -C(O)-, which means that J-4 is the fragment shown below.

When the variable J is defined as -CH2(cyclopropyl) substituted with one cyano group, it means that J is the moiety shown below (i.e. the cyano group can be attached to either the methylene group or to any carbon atom of the cyclopropyl ring) .

The total number of carbon atoms in a substituent group is indicated using the prefix Ci-Cj. For example, C ₁ -C ₄ alkyl refers to methyl, ethyl and various isomers of propyl and butyl.

When a compound is substituted with a substituent bearing a subscript indicating that the number of said substituents may exceed 1, said substituents (when the number exceeds 1) are independently selected from a group of specified substituents. In addition, when the subscript indicates a range, for example (R)i_j, then the number of substituents can be selected from integers between i and j inclusive. When a group contains a substituent which may be hydrogen, then this substituent is taken to be hydrogen and is considered to be equivalent to the group being unsubstituted. When one or more positions in a group are indicated to be non-substituted or unsubstituted, then hydrogen atoms are added to saturate any free valency.

When the substituent is a 5- or 6-membered nitrogen-containing heterocyclic ring, it may be attached to the remainder of the compound of Formula 1 through any available ring carbon or nitrogen atom unless otherwise described.

A wide variety of synthetic methods are known for the preparation of aromatic and non-aromatic heterocyclic rings and ring systems; for more detailed information see volume eight of Comprehensive Heterocyclic Chemistry, A.R. Katritzky, C.W. Rees editors-in-chief, Pergamon Press, Oxford, 1984; and the twelfth volume of Comprehensive Heterocyclic Chemistry II, A.R. Katritzky, C.W. Rees, E.F.V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.

The compounds of this invention may exist in the form of one or more stereoisomers. Stereoisomers are isomers with the same chemical structure but differing in the arrangement of their atoms in space, and they include enantiomers, diastereomers, cis-trans isomers (also known as geometric isomers) and atropoisomers. Atropoisomers arise from limited rotation around single bonds when the rotational barrier is high enough to permit isolation of isomeric compounds. It will be apparent to one skilled in the art that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). In addition, one skilled in the art knows how to separate, enrich and/or selectively obtain said stereoisomers. For a comprehensive discussion of all aspects of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

Compounds selected from compounds of formula 1 generally exist in more than one form, and therefore a compound of formula 1 includes all crystalline and non-crystalline forms of the compounds that formula 1 represents. Non-crystalline forms include embodiments that are solids such as waxes and resins, and embodiments that are liquids such as solutions and melts. Crystal forms include embodiments that are essentially single crystal types, and

- 4 043836 embodiments that are a mixture of polymorphs (ie, different crystal types). The term polymorph refers to a specific crystalline form of a chemical compound that can crystallize into different crystalline forms, with these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs may have the same chemical composition, they may also differ in composition due to the presence or absence of cocrystallization water or other molecules that may be weakly or strongly bound in the lattice. Polymorphs may differ in chemical, physical and biological properties such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspension, dissolution rate and bioavailability. It will be apparent to one skilled in the art that a polymorph of a compound represented by Formula 1 may exhibit beneficial effects (eg, availability in suitable dosage forms, improved biological performance) compared to another polymorph or mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of the compound represented by Formula 1 can be accomplished by methods known to those skilled in the art, including, for example, crystallization using selected solvents and temperatures. The compounds of this invention may exist in the form of one or more crystalline polymorphs. This invention includes both individual polymorphs and mixtures of polymorphs, including mixtures enriched in one polymorph relative to other polymorphs. A detailed discussion of the phenomenon of polymorphism is given in the monograph R. Hilfiker, ed., Polymorphism In the Pharmaceutical Industry, Wiley-VCH, Weinheim, 2006.

The embodiments of the present invention described in the Summary section include the embodiments described below. In the following embodiments, reference to a compound of Formula 1 includes the definitions of the substituents set forth in the Summary of the Invention unless they are further defined in the embodiments.

Embodiment 1. A compound of formula 1, wherein J is J-1.

Embodiment 1a. The compound of Embodiment 1, wherein R ² is C ₁ -C ₄ alkyl, unsubstituted or substituted with substituents selected from OMe, SMe, S(O)Me and SO ₂ Me.

Embodiment 1b. The compound of embodiment 1a, wherein R ² is C1-C ₄ alkyl substituted with OMe, SMe, S(O)Me or SO ₂ Me.

Embodiment 1c. The compound of embodiment 1a, wherein R ² is C1- _C4 alkyl.

Embodiment 1d. The compound of embodiment 1c, wherein R ² is methyl.

Embodiment 1e. The compound of any one of embodiments 1-1d, wherein R ³ is H or methyl.

Embodiment 1f. The compound of any one of embodiments 1-1d, wherein R ⁴ is H, C1-C2 alkyl or C1-C2 haloalkyl.

Embodiment 2: A compound of Formula 1 wherein J is J-2.

Embodiment 2a. The compound of embodiment 2 or 2a, wherein R ⁵ is H or methyl.

Embodiment 2b. The compound of embodiment 2a, wherein R ⁵ is methyl.

Embodiment 2c. The compound of embodiment 2a, wherein R ⁵ is H.

Embodiment 2d. The compound of any one of embodiments 2-2c, wherein Q is pyridinyl or pyrimidinyl.

Embodiment 2e. The compound of embodiment 2d, wherein Q is pyridinyl.

Embodiment 2f. The compound of embodiment 2d, wherein Q is pyrimidinyl.

Embodiment 2g. The connection as in any one of embodiments 2-2f, wherein J-2 is

R ⁵

J-2a

- 5 043836

Embodiment 3: Composition consisting of a compound of formula 1 wherein J is J-2a and a compound of formula 1 wherein J is J-2b

J-2a J-2b wherein the ratio of the compound of formula 1 where J is J-2a to the compound of formula 1 where J is J-2b is greater than 60:40.

Embodiment 3a. The composition of Embodiment 3, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 80:20.

Embodiment 3b. The composition of Embodiment 3, wherein the ratio of the compound of Formula 1 wherein J is J-2a to the compound of Formula 1 wherein J is J-2b is greater than 90:10.

Embodiment 3c. The composition of Embodiment 3, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 95:5.

Embodiment 3d. The composition of Embodiment 3, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 99:1.

Embodiment 3e. A composition consisting of a compound of formula 1, where J is J-2a, and a compound of formula 1, where J is J-2b

R ⁵ R ⁵

J-2a J-2b and R ⁵ is methyl;

wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 60:40.

Embodiment 3f. The composition of Embodiment 3e, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 80:20.

Embodiment 3g. The composition of Embodiment 3e, wherein the ratio of the compound of Formula 1 wherein J is J-2a to the compound of Formula 1 wherein J is J-2b is greater than 90:10.

Embodiment 3h. The composition of Embodiment 3e, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 95:5.

Embodiment 3i. The composition of Embodiment 3e, wherein the ratio of the compound of Formula 1 wherein J is J-2a to the compound of Formula 1 wherein J is J-2b is greater than 99:1.

Embodiment 3j. A composition consisting of a compound of formula 1, where J is J-2a, and a compound of formula 1, where J is J-2b

R ⁵ R ⁵

J-2a J-2b and Q is pyridinyl;

wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 60:40.

Embodiment 3k. The composition of Embodiment 3j, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 80:20.

Embodiment 3l. The composition of Embodiment 3j, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 90:10.

Embodiment 3 m. The composition of Embodiment 3j, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 95:5.

Embodiment 3n. The composition of Embodiment 3j, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 99:1.

Embodiment 3o. A composition consisting of a compound of formula 1, where J is J-2a, and a compound of formula 1, where J is J-2b

R ⁵ R ⁵

J-2a J-2b and Q is pyrimidinyl;

wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 60:40.

Embodiment 3p. The composition of Embodiment 3o, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 80:20.

Embodiment 3q. The composition of Embodiment 3o, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 90:10.

Embodiment 3r. The composition of Embodiment 3o, wherein the ratio of the compound of formula 1 wherein J is J-2a to the compound of formula 1 wherein J is J-2b is greater than 95:5.

Embodiment 3s. The composition of Embodiment 3o, wherein the ratio of the compound of Formula 1 wherein J is J-2a to the compound of Formula 1 wherein J is J-2b is greater than 99:1.

Embodiment 4: Compound of formula 1 wherein J is J-3.

Embodiment 4a. The compound of embodiment 4, wherein R ⁶ is H.

Embodiment 4b. The compound of embodiment 4, wherein R ⁷ is C1- _C4 alkyl.

Embodiment 4c. The compound of embodiment 4b, wherein R ⁷ is methyl or ethyl.

Embodiment 4d. The compound of embodiment 4c, wherein R ⁷ is methyl.

Embodiment 5. A compound of Formula 1 or Embodiment 1, wherein J is J-4.

Embodiment 5a. The compound of Embodiment 5, wherein X is -O-.

Embodiment 5b. The compound of Embodiment 5, wherein X is -CO)-.

Embodiment 5c. The compound of embodiment 5, 5a or 5b, wherein R ⁸ is C1-C2 alkyl or C1- _C2 haloalkyl.

Embodiment 5d. The compound of embodiment 5c, wherein R ⁸ is methyl or ethyl.

Embodiment 5e. The compound of embodiment 5d, wherein R ⁸ is methyl.

Embodiment 6. Compound of formula 1, wherein J is J-5.

Embodiment 6a. The compound of embodiment 6, wherein R ¹⁴ is C1-C4 alkyl.

Embodiment 6b. The compound of embodiment 6a wherein R ¹⁴ is methyl or ethyl.

Embodiment 6c. The compound of embodiment 6b wherein R ¹⁴ is methyl.

Embodiment 6d. The compound of any one of embodiments 6-6c, wherein R ¹⁵ represents C1-C4 alkyl.

Embodiment 6e. The compound of embodiment 6d, wherein R ¹⁴ is methyl or ethyl.

Embodiment 6f. The compound of embodiment 6e, wherein R ¹⁴ is methyl.

- 7 043836

Embodiment 6g. The connection as in any one of embodiments 6-6f, wherein J-5 is

О % ✓ ^R ' ^{5 Z} о

R ¹⁴

J-5a

Embodiment 7: Composition consisting of a compound of formula 1 wherein J is J-5a and a compound of formula 1 wherein J is J-5b

wherein the ratio of the compound of formula 1 wherein J is J-5a to the compound of formula 1 wherein J is J-5b is greater than 60:40.

Embodiment 7a. The composition of Embodiment 7, wherein the ratio of the compound of formula 1 wherein J is J-5a to the compound of formula 1 wherein J is J-5b is greater than 80:20.

Embodiment 7b. The composition of Embodiment 7, wherein the ratio of the compound of formula 1 wherein J is J-5a to the compound of formula 1 wherein J is J-5b is greater than 90:10.

Embodiment 7c. The composition of Embodiment 7, wherein the ratio of the compound of Formula 1 wherein J is J-5a to the compound of Formula 1 wherein J is J-5b is greater than 95:5.

Embodiment 7b. The composition of Embodiment 7, wherein the ratio of the compound of Formula 1 wherein J is J-5a to the compound of Formula 1 wherein J is J-5b is greater than 99:1.

Embodiment 8: Compound of Formula 1 wherein J is J-6.

Embodiment 8a. The compound of embodiment 8, wherein R ¹⁶ is F, methyl or amino.

Embodiment 8b. The compound of embodiment 8a wherein R ¹⁶ is methyl.

Embodiment 9. A compound of formula 1, wherein J is C ₂ -C ₄ alkyl substituted with one cyano group.

Embodiment 9a. The compound of Embodiment 9, wherein J is ethyl substituted with one cyano group.

Embodiment 9b. The compound of embodiment 9a, wherein J is -CH(CN)CH ₃ .

Embodiment 10. A compound of formula 1, wherein J is -CH ₂ (cyclopropyl) substituted with one cyano group.

Embodiment 10a. The compound of Embodiment 10, wherein J is -CH(CN)(cyclopropyl).

Embodiment 11. A compound of formula 1, wherein J is cyclopropyl, unsubstituted or substituted with one cyano group or one C(O)NHR ¹⁷ group.

Embodiment 11a. The compound of Embodiment 11, wherein J is cyclopropyl.

Embodiment 11b. The compound of Embodiment 11, wherein J is 1-(cyano)cyclopropyl.

Embodiment 11c. A compound of formula 1, wherein J is C2-C4 alkyl substituted with one cyano group; or cyclopropyl.

Embodiment 12. The compound of formula 1 or any of embodiments 1-11c, wherein R ^1a is Cl.

Embodiment 12a. The compound of Formula 1 or any of embodiments 1-11c, wherein R ^1a is CF3.

Embodiment 13. The compound of formula 1 or any of embodiments 1-12a, wherein R ^1b is H.

Embodiment 13 a. The compound of formula 1 or any of embodiments 1-12a, where R ^1b represents Cl.

Embodiment 14. The compound of formula 1 or any of embodiments 1-11c,

- 8 043836 where R ^1a represents H and R ^1b represents CF ₃ .

Embodiment 15. The compound of formula 1 or any of embodiments 1-11c, wherein R ^1a is Cl and R ^1b is Cl.

Embodiment 16. The compound of formula 1 or any of embodiments 1-11c, wherein R ^1a is Cl and R ^1b is CF ₃ .

Embodiment 17. A compound of formula 1 or any of embodiments 1-11c, wherein R ^1a is H and R ^1b is CF3, or R ^1a is Cl and R ^1b is Cl, or R ^1a is Cl and R ^1b is CF3.

Embodiment 17a. A compound of formula 1 or any of embodiments 1-11c, wherein R ^1a is H and R ^1b is CF ₃ or R ^1a is Cl and R ^1b is Cl.

Embodiment 18. Composition consisting of a compound of formula 1-1S and a compound of formula 1-1R

1-1S 1-1R wherein the ratio of the compound of formula 1-1S to the compound of formula 1-1R is greater than 60:40.

Embodiment 18a. The composition of Embodiment 18, wherein the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 80:20.

Embodiment 18b. The composition of Embodiment 18, wherein the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 90:10.

Embodiment 18c. The composition of Embodiment 18, wherein the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 95:5.

Embodiment 18d. The composition of Embodiment 18, wherein the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 99:1.

Embodiment 19. Composition consisting of a compound of formula 1-1S and a compound of formula 1-1R

1-1S 1-1R wherein the ratio of the compound of formula 1-1S to the compound of formula 1-1R is greater than 60:40.

Embodiment 19a. The composition of Embodiment 19, wherein J is J-1.

Embodiment 19b. The composition of Embodiment 19, wherein J is J-2.

Embodiment 19c. The composition of embodiment 19b, wherein J is J-2a

J-2a

Embodiment 19d. The composition of Embodiment 19, wherein J is J-3.

Embodiment 19e. The composition of Embodiment 19, wherein J is J-4.

Embodiment 19f. The composition of Embodiment 19, wherein J is J-5.

- 9 043836

Embodiment 19g. The composition of embodiment 19f, wherein J is

J-5a o CHU JL R ¹⁵ '^1 o

R ¹⁴

J-5a

Embodiment 19h. The composition of Embodiment 19, wherein J is J-6.

Embodiment 19i. The composition of embodiment 19, wherein J is a C2-C4 alkyl substituted with one cyano group.

Embodiment 19j. The composition of embodiment 19, wherein J is -CH2(cyclopropyl) substituted with one cyano group.

Embodiment 19k. The composition of embodiment 19, wherein J is cyclopropyl, unsubstituted or substituted with one cyano group or one C(O)NHR ¹⁷ group.

Embodiments 20-20k are identical to embodiments 19-19k except that the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 80:20.

Embodiments 21-21k are identical to embodiments 19-19k except that the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 90:10.

Embodiments 22-22k are identical to embodiments 19-19k except that the ratio of the compound of Formula 1-1S to the compound of Formula 1-1R is greater than 95:5.

Embodiments 23-23k are identical to embodiments 19-19k except that the ratio of compound of Formula 1-1S to compound of Formula 1-1R is greater than 99:1.

Embodiments of this invention, including embodiments 1-23k above, as well as any other embodiments described herein, may be combined in any manner, and the descriptions of the variables in the embodiments apply not only to the compounds of formula 1, but also to the parent compounds and intermediates used to prepare the compounds of formula 1. In addition, embodiments of this invention, including embodiments 1-23k above, as well as any other embodiments described herein, and any combination thereof, are included in the compositions and methods of the present invention.

Illustrative combinations of embodiments 1-23k are the following combinations.

Embodiment A. Compound of formula 1, wherein J is J-1, J-2 or J-5.

Embodiment B. The connection of Embodiment A, wherein J is J-1.

Embodiment C. The compound of Embodiment B, wherein R ² is C1-C4 alkyl.

Embodiment D. The compound of Embodiment C wherein R ² is methyl.

Embodiment E. The compound of Embodiment A, wherein J is J-2.

Embodiment F. The compound of Embodiment E wherein R ⁵ is H or methyl.

Embodiment G. The compound of Embodiment F, wherein Q is pyridinyl or pyrimidinyl.

Embodiment H. The connection of any one of Embodiments E, F, or G, wherein J-2 is

R ⁵

J-2a

Embodiment I. The compound of Embodiment A, wherein J is J-5.

Embodiment J. The compound of Embodiment I, wherein R ¹⁴ is C1-C4 alkyl.

Embodiment K. The connection of any one of Embodiments I or J, wherein J-5 is

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Embodiment L. The compound of any one of Embodiments A-K, wherein the compound of Formula 1 is a compound of Formula 1-1S

Embodiment M. Compound of formula 1, wherein J is C ₂ -C ₄ alkyl substituted with one cyano group; -CH ₂ (cyclopropyl) substituted with one cyano group; or cyclopropyl, unsubstituted or substituted with one cyano group or one C(O)NHR ¹⁷ group; or J-1, J-2 or J-5.

Embodiment N. The compound of Embodiment M, wherein R ^1a is Cl and R ^1b is Cl; or R ^1a is CF3 and R ^1b is H.

Embodiment O. The compound of Embodiment N, wherein J is C ₂ -C ₄ alkyl substituted with one cyano group; or cyclopropyl.

Embodiment P. The compound of Embodiment N, wherein J is J-1.

Embodiment Q. The compound of Embodiment P, wherein R ² is methyl; R ³ represents H or methyl; and R ⁴ is H or methyl.

Embodiment R. The compound of Embodiment N, wherein J is J-2.

Embodiment S. The compound of Embodiment R, wherein ^R5 is H or methyl; and Q is pyridinyl or pyrimidinyl.

Embodiment T. Connection according to Embodiment S, where J-2 is 'Q

R ⁵

J-2a

Embodiment U. The connection of Embodiment N, wherein J is J-5.

Embodiment V. The compound of Embodiment U, wherein R ¹⁴ is H or methyl; and R ¹⁵ represents C1- _C4 alkyl.

Embodiment W. The connection of Embodiment V, wherein J-5 is

Embodiment L-1. Compound of formula 1-1S

Embodiment L-2. A compound of formula 1-1S, wherein J is C ₂ -C ₄ alkyl substituted with one cyano group; -CH ₂ (cyclopropyl) substituted with one cyano group; or cyclopropyl, unsubstituted or substituted with one cyano group or one C(O)NHR ¹⁷ group; or J-1, J-2 or J-5.

Embodiment L-3. The compound of Embodiment L-2, wherein R ^1a is Cl and R ^1b is Cl; or R ^1a is CF3 and R ^1b is H.

Embodiment L-4. The compound of Embodiment L-3, wherein J is C ₂ -C ₄ alkyl substituted with one cyano group; or cyclopropyl.

Embodiment L-5. The connection of embodiment L-3, where J is J-1.

Embodiment L-6. The compound of embodiment L-5, wherein R ² is methyl; R ³ represents H or methyl; and R ⁴ is H or methyl.

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Embodiment L-7. The connection of embodiment L-3, where J is

J-2.

Embodiment L-8. The compound of Embodiment L-7, wherein R5 is H or methyl; and Q is pyridinyl or pyrimidinyl.

Embodiment L-9. The connection of embodiment L-8, where J-2 is

R ⁵

J-2a

Embodiment L-10. The connection of embodiment L-3, where J is J-5.

Embodiment L-11. The compound of embodiment L-10, wherein R ¹⁴ is H or methyl; and R ¹⁵ represents C1- _C4 alkyl.

Embodiment L-12. The connection of embodiment U, where J-5 is

Specific embodiments include compounds of formula 1 selected from the group consisting of compounds 1, 3, 8, 10, 11, 19, 20, 33, 34, 39, 50, 61, 67, 69, 70 and 71. Compound numbers are provided in the indicator tables. Thus, specific embodiments include compounds of formula 1 selected from the group consisting of a compound of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-1, R ² is methyl, R ³ is H and R ⁴ represents H (compound 1);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-1, R ² is methyl, R ³ is H and R ⁴ is methyl (compound 3);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-2, R ⁵ is H and Q is 2-pyrimidinyl (compound 10);

compounds of formula 1 wherein R ^1a is CF ₃ , R ^1b is Cl, J is J-2, R ⁵ is H and Q is 2-pyrimidinyl (compound 11);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-2, R ⁵ is methyl and Q is 2-pyrimidinyl (compound 19);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-2a, R ⁵ is methyl and Q is 2-pyridinyl (compound 20);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-3, R ⁶ is H and R ⁷ is methyl (compound 33);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-4, X is O and R ⁸ is ethyl (compound 34);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl, J is J-5a, R ¹⁴ is methyl and R ¹⁵ is methyl (compound 39);

compounds of formula 1 wherein R ^1a is CF ₃ , R ^1b is H, J is J-2, R ⁵ is H and Q is 2-pyrimidinyl (compound 50);

compounds of formula 1 wherein R ^1a is CF ₃ , R ^1b is H and J is cyclopropyl (compound 67);

compounds of formula 1 wherein R ^1a is CF ₃ , R ^1b is H and J is 1-(cyano)ethyl (compound 69);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl and J is cyclopropyl (compound 70);

compounds of formula 1 wherein R ^1a is Cl, R ^1b is Cl and J is 1-(cyano)ethyl (compound 71);

compounds of formula 1-1S wherein R ^1a is Cl, R ^1b is Cl, J is J-1, R ² is methyl, R ³ is H and R ⁴ is H (compound 8); and compounds of formula 1-1S wherein R ^1a is Cl, R ^1b is Cl, J is J-2, R ⁵ is H and Q is 2-pyrimidinyl (compound 61).

It should be noted that the compounds of this invention have favorable metabolic characteristics and/or persistence properties in soil and are active in controlling a wide range of agronomic and non-agricultural invertebrate pests.

Particularly noteworthy are embodiments of the invention relating to the control of a wide range of invertebrate pests and its economic importance, to the protection of crops from damage or injury caused by invertebrate pests. The compounds of this invention, due to their beneficial properties related to the ability to move in plants and their systemic action, also protect foliage or other parts of plants that are not directly in contact with the compound of formula 1 or a composition containing the compound.

Bioaccumulation of pesticides in non-target organisms is an important safety concern, and limiting systemic exposure and/or accumulation of pesticides and/or their metabolites in non-target organisms is often desirable. For example, if a compound is to be used as an insecticide on crops, it is desirable that the compound does not accumulate in the plasma or fat of vertebrate animals.

The compounds of formula 1 may exhibit favorable pharmacokinetic properties when administered to vertebrate animals. In particular, the compounds of Formula 1 have been found to have rapid clearance from the plasma/blood of the vertebrate animal and low distribution in the adipose tissue of the vertebrate animal, thereby reducing the likelihood of unwanted bioaccumulation. Note the fluorine atom at the 4-position of the phenyl ring attached at the 5-position of the isoxazoline ring.

The pharmacokinetic properties of the compounds of formula 1 can be determined using a variety of analytical methods known in pharmacology. In one exemplary method, which uses a single oral dose, three male and three female rats are gavaged with a single dose of a test substance. Blood is collected from the tail vein at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours and then every 24 hours until the time of sacrifice. To obtain plasma samples, blood is collected into tubes containing ethylenediaminetetraacetic acid (EDTA) and centrifuged at approximately 3000 rpm to separate the plasma from the red blood cells. Alternatively, blood is collected using microcapillaries and transferred into tubes containing a mixture of EDTA:water (1:1, by volume). In addition, at the time of sacrifice, the fat is collected, homogenized and subjected to extraction to determine the concentration of the compound of formula 1. Plasma or blood and fat are analyzed for the content of the compound of formula 1 and/or metabolites, for example, by high performance liquid chromatography (HPLC) with tandem mass detection. spectrometry (LC/MS/MS) with determination of the concentration of the test compound. Pharmacokinetic data for plasma or blood are analyzed using a nonlinear modeling computer program (e.g., Phoenix® WinNonlin®, Pharsight-A Certara™ Company, St. Louis, MO, U.S.A.) to determine the plasma/blood half-life of the compound of formula 1, time after administration, when maximum plasma/blood concentration (Tmax), maximum plasma/blood concentration (Cmax), and area under the plasma/blood concentration curve (AUC) are reached. Since fat analysis requires sacrifice of the rat, fat data is obtained at a single point in time (ie, the time of sacrifice of the rat). The concentration ratio of the compound of formula 1 fat:plasma or fat:blood is then determined.

Also noteworthy as embodiments of the present invention are compositions comprising a compound according to any of the preceding embodiments, as well as any other embodiments described in the invention, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, wherein said compositions optionally further include at least one additional biologically active compound or agent.

In addition, also noteworthy as embodiments of the present invention are invertebrate pest control compositions comprising compounds of any of the preceding embodiments, as well as any other embodiments described in the invention, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, wherein said compositions optionally further include at least one additional biologically active compound or agent. Embodiments of the invention further include methods for controlling an invertebrate pest, comprising contacting the invertebrate pest or its habitat with a biologically effective amount of a compound according to any of the preceding embodiments (eg, in the form of a composition described herein).

Embodiments of the invention also include a composition containing a compound of any of the preceding embodiments in the form of a liquid soil drench. Embodiments of the invention further include methods for controlling an invertebrate pest comprising contacting soil with a liquid composition in the form of a soil drench comprising a biologically effective amount of a compound according to any of the preceding embodiments.

Embodiments of the invention also include a sprayable composition for combating

- 13 043836 invertebrate pest, comprising a biologically effective amount of a compound according to any of the preceding embodiments and a propellant. In addition, embodiments of the invention include a bait composition for controlling an invertebrate pest, comprising a biologically effective amount of a compound according to any of the preceding embodiments, one or more nutrients, optionally an attractant, and optionally a humectant. Embodiments of the invention also include an apparatus for controlling an invertebrate pest, including said bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to allow the invertebrate pest to pass through the opening, thereby wherein the invertebrate pest can access said bait composition from its location outside the housing, and wherein the housing is further adapted to be located at or adjacent to a site of potential or known invertebrate pest activity.

Embodiments of the invention also include methods for protecting seeds from an invertebrate pest, comprising contacting the seeds with a biologically effective amount of a compound according to any of the preceding embodiments.

Embodiments of the invention also include methods for controlling an invertebrate pest, comprising contacting the invertebrate pest or its habitat with a biologically effective amount of a compound of Formula 1 (e.g., in the form of a composition described herein), provided that the methods are not methods for therapeutically treating a human body.

This invention also relates to such methods in which the invertebrate pest or its habitat is contacted with a composition comprising a biologically effective amount of a compound of formula 1, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, wherein the composition optionally further includes a biologically effective amount of at least one additional biologically active compound or agent, provided that the methods are not methods of therapeutic treatment of the human body.

The compounds of Formula 1 can be prepared by one or more of the following methods and from the options described in Schemes 1-11. The definitions of substituents in the compounds of formulas 1-15 below are the same as the above definitions in the Summary of the Invention section, unless otherwise indicated. The compounds of formulas 1a and 1b are subsets of the compounds of formula 1, and all substituents for formulas 1a and 1b are defined above for formula 1. The following abbreviations may be used: DMF is N,N-dimethylformamide, and DBU is 1,8-diazabicyclo [5,4,0]undec-7-ene.

Compounds of formula 1a (formula 1, where J is J-1, J-2, J-4, J-5 or J-6) can be prepared from compounds of formula 2 using the method presented in Scheme 1. In this method , a carboxylic acid of formula 2 is coupled with an amine compound of formula 3 (where J is J-1, J-2, J-4, J-5 or J-6), typically in the presence of a dehydrating reagent to effect the coupling reaction . Coupling reagents that can be used in this method include dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and carbonyldiimidazole. Additional coupling reagents that can be used in this method include 1-propanephosphonic acid cyclic anhydride, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3 -hexafluorophosphate oxide and N-[(dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide; these coupling reagents are typically used in the presence of a base such as triethylamine, pyridine, 4-(dimethylamino)pyridine or N,N-diisopropylethylamine. Typical reaction conditions include an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran or DMF, and a reaction temperature from room temperature to 70°C.

1a

Jis J-1, J-2, J-4, J-5 or J-6

Scheme 1

Compounds of formula 1a can also be prepared by converting carboxylic acids of formula 2 into their corresponding acid chlorides and then coupling the acid chlorides with amines of formula 3. The method in Scheme 1 is illustrated in Step C of Synthesis Example 1 and Synthesis Examples 2 and 4.

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Compounds of formula 1a (formula 1, where J is J-1, J-2, J-4, J-5 or J-6) can also be prepared by the method shown in Scheme 2. In this method, the aryl bromide or aryl iodide of formula 4 carbonylated and coupled with an amine compound of formula 3 (where J is J-1, J-2, J-4, J-5 or J-6).

Scheme 2

This aminocarbonylation method typically involves treating an aryl bromide of formula 4 (where X is Br or I) with an amine of formula 3 in the presence of a palladium catalyst under a CO (carbon monoxide) atmosphere. Palladium catalysts used in this method typically include palladium in the formal oxidation state of either 0 (ie Pd(0)) or 2 (ie Pd(II)). Examples of palladium-containing compounds and complexes used as catalysts in this method include PdCl ₂ (PPh ₃ ) ₂ (bis(triphenylphosphine) palladium(II) dichloride), Pd(PPh ₃ ) ₄ (tetrakis(triphenylphosphine) palladium(0)) , Pd(C ₅ H ₇ O ₂ ) ₂ (palladium(I) acetylacetonate), Pd ₂ (dba) ₃ (tris(dibenzylideneacetone)dipalladium(0)) and [1,1 '-bis(diphenylphosphino)ferrocene]dichloropalladium( P). The Scheme 2 method is usually carried out in the liquid phase using a palladium catalyst having good solubility in the liquid phase. Solvents used as the liquid phase include ethers such as 1,2-dimethoxyethane, amides such as N,N-dimethylacetamide, and non-halogenated aromatic hydrocarbons such as toluene.

The Scheme 2 method can be carried out over a wide temperature range from approximately 25°C to approximately 150°C. Temperatures from about 60°C to about 110°C are preferred, which generally provide faster reaction rates and higher yields. Examples of publications that describe aminocarbonylation methods include H. Horino et al., Synthesis, 1989, 715; and J.J. Li, G.W. Gribble, editors, Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist, 2000. The method of Scheme 2 is illustrated in Step B of Synthesis Example 5.

Compounds of formula 1 wherein J is (i) C2-C4 alkyl substituted with one cyano group;

(ii) -CH ₂ (cyclopropyl) substituted with one cyano group; or (iii) cyclopropyl, unsubstituted or substituted with one cyano group or one C(O)NHR ¹⁷ group, can be prepared by methods similar to those described in Schemes 1 and 2.

Compounds of formula 1b (formula 1, where J is J-3) can be prepared from compounds of formula 5 using the method shown in Scheme 3. In this method, the amide of formula 5 is treated with a suitably substituted amine of formula 6.

1b

J is J-3

Scheme 3

The Scheme 3 method can be carried out by treating the amide of Formula 5 with DMF-DMA at temperatures ranging from about 25 to about 110 °C, then coupling with the amine of Formula 6 or its corresponding salt. Compounds of formula 1b can also be prepared in one step by treating the amide of formula 5 with triethyl orthoformate and the amine of formula 6 or its corresponding salt in toluene. Examples of publications that describe this method include T. Mita et al., WO 2009/005015; W. Zhao et al., Org. Lett., 2011, 5160; and Y. Kusuoka et al., WO 2014/126208. The method of Scheme 3 is illustrated in Step B of Synthesis Example 3.

Compounds of formula 5 can be prepared from the corresponding carboxylic acids of formula 2, as shown in the method of scheme 4.

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Scheme 4

The transformation, summarized in Scheme 4, is described in detail in the literature and involves the coupling of carboxylic acids with ammonia sources, such as ammonium carbonate, through the corresponding acid chlorides. Alternatively, the coupling reaction can be directly carried out in the presence of coupling reagents such as HBTU in solvents such as THF or dioxanes. The method of Scheme 4 is illustrated in Step A of Synthesis Example 3.

Compounds of Formula 2 can be prepared by hydrolysis of esters of Formula 7 (where R ^a is methyl or ethyl) as shown in Method Scheme 5.

Scheme 5

In this method, the ester of formula 7 is converted to the corresponding carboxylic acid of formula 2 according to well known procedures. For example, treatment of the ester of Formula 7 with an aqueous solution of lithium hydroxide in tetrahydrofuran followed by acidification gives the corresponding carboxylic acid of Formula 2. The method of Scheme 5 is illustrated in Step B of Synthesis Example 1.

Compounds of formula 7 can be prepared by the 1,3-dipolar addition of styrenes of formula 8 to nitrile oxides formed from oximes of formula 9, as shown in the method of scheme 6.

Scheme 6

This method typically involves chlorination of an oxime of formula 9 and subsequent dehydrochlorination to produce an in situ formed nitrile oxide, which then undergoes a 1,3-dipolar addition of styrenes of formula 8 to produce a compound of formula 7. In a typical procedure, a chlorinating reagent such as sodium hypochlorite, N-chlorosuccinimide or chloramine-T is reacted with an oxime of formula 9 in the presence of styrene of formula 8. Depending on the reaction conditions, the presence of an amine base such as pyridine or triethylamine may be necessary to facilitate the dehydrochlorination reaction. Solvents used in this method include tetrahydrofuran, diethyl ether, methylene chloride, dioxane and toluene. Reaction temperatures vary from room temperature to the boiling point of the solvent. General procedures for the cycloaddition of nitrile oxides and olefins are described in Lee, Synthesis, 1982, 6, 508-509; Kanemasa et al., Tetrahedron, 2000, 56, 1057-1064; EP 1538138 A1, as well as in the literature cited in these publications. The method of Scheme 6 is illustrated in Step A of Synthesis Example 1.

Compounds of formulas 8 and 9 are commercially available or are well known compounds, see, for example, T. Mita et al., US 7951828; and G. Lahm et al., WO 2007/079162.

Compounds of formula 4 can be prepared by the 1,3-dipolar addition of styrenes of formula 8 to nitrile oxides formed by oximes of formula 10, as shown in the method of Scheme 7.

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Scheme 7

The method in Scheme 7 is similar to the method in Scheme 6. Oximes of formula 10 are commercially available or are well-known compounds; see, for example, G. Lahm et al., WO 2007/079162. The method of Scheme 7 is illustrated in Step A of Synthesis Example 5.

Compounds of formula 7 can also be prepared by cyclization of compounds of formula 11 with hydroxylamine, as shown in the method of scheme 8.

Scheme 8

In this method, isoxazolines of formula 7 can be prepared by treating ketones of formula 11 with hydroxylamine or a salt thereof in the presence of an aqueous solution of a base such as NaOH, Cs ₂ CO ₃ or K ₂ CO ₃ in a solvent such as dichloroethane, chloroform or THF. Examples of this method are described in the publications G. Annis, WO 2009/126668; and K. Matoba et al., Angew. Chem. Int., ed., 2010, 49(33), 5762.

Compounds of formula 11 can be prepared by the condensation reaction of compounds of formula 12 with naphthalene ketones of formula 13, as shown in the method of scheme 9.

Scheme 9

This method involves reacting a compound of formulas 12 and 13 in the presence of a base such as Ca(OH) ₂ , K ₂ CO ₃ , CsCO ₃ , in a solvent such as toluene, DMF, MTBE, trifluoromethylbenzene or acetonitrile, or a mixture of such solvents. Typical reaction temperatures range from about 60°C to about 130°C. An example of this method is described in G. Annis, WO 2009/126668.

Compounds of formulas 12 and 13 are commercially available or are well known compounds; see, for example, Chunhua Yang et al., WO 2017/176948; D. Leysen et al., WO 2005/082236; and F. Cohen et al., WO 2006/069063.

Compounds of formula 4 can also be prepared by cyclizing compounds of formula 14 with hydroxylamine as shown in method Scheme 10.

Scheme 10

This method is similar to the method described in Scheme 8. Similar treatment of compounds of formula 14 with hydroxylamine gives isoxazolines of formula 4.

Compounds of formula 14 can be prepared by the condensation reaction of compounds of formula 12 and naphthalene ketones of formula 15, as shown in the method of scheme 11.

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Scheme 11

This method is similar to the method described in Scheme 9. Similar treatment of compounds of formula 12 and naphthalene ketones of formula 15 with a base gives compounds of formula 14. Compounds of formulas 12 and 15 are commercially available or are known in the aggyls; see, for example, D. Leysen et al., WO 2005/082236; and F. Cohen et al., WO 2006/069063.

It should be understood that some of the reagents and reaction conditions described above for preparing the compounds of Formula 1 may be incompatible with the particular functional groups present in the intermediates. In these cases, when obtaining the desired products, this problem can be solved by using protective group installation/deprotection or functional group interconversion reactions in the synthetic sequences. The use and selection of protecting groups is well known to those skilled in the art of chemical synthesis (see, for example, Greene, T.W., Wuts, P.G.M., Protective Groups in Organic Synthesis, 2nd ed., Wiley: New York, 1991). It will be apparent to one skilled in the art that in some cases, following administration of the reagents depicted in the individual schemes, additional standard synthetic steps, which are not described in detail, may be required to complete the synthesis of the compound of formula 1. It will be apparent to one skilled in the art that it may be necessary to carry out a combination of the steps illustrated in the above schemes in an order that differs from the order expected by the particular reaction sequence presented for the preparation of the compounds of formula 1.

It will also be apparent to one skilled in the art that the compounds of formula 1 and intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation and reduction reactions to add substituents or modify existing substituents.

It is believed that one skilled in the art, using the above description, can, without further study, use the present invention to its fullest extent. Therefore, the synthetic examples presented below should be construed as illustrative only and should not be construed as limiting the invention in any way. The steps in the following synthetic examples illustrate the methodology for each step in the overall chemical transformation process, and the starting material for each step may not necessarily be obtained by performing a particular preparative synthesis, the procedure for which is described in other examples or steps. Data expressed as percentages are by weight, except for mixtures of chromatographic solvents or unless otherwise noted. Data for mixtures of chromatographic solvents, expressed in parts and percentages, are given by volume unless otherwise noted. 1H NMR spectra are recorded in ppm (parts per million) relative to tetramethylsilane; s denotes singlet, d denotes doublet, t denotes triplet, kv denotes quartet, m denotes multiplet, dd denotes doublet of doublets, de denotes doublet of triplets, w.s denotes broadened singlet. DMF stands for N,N-dimethylformamide. Compound numbers are indicated in indicator tables A-G.

Synthesis example 1.

Preparation of N-[(1R)-2-amino-1-methyl-2-exoethyl]-4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5(trifluoromethyl)-3 -isoxazolyl]-1-naphthalenecarboxamide (compound 1).

Step A. Preparation of methyl 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3isoxazolyl]-1-naphthalene-carboxylate.

N-chlorosuccinimide (1.05 g, 7 .86 mmol). This mixture was stirred for 1.5 hours at room temperature, and then a solution of 1,3-dichloro4-fluoro-5-[1-(trifluoromethyl)ethenyl]benzene (2.04 g, 7.86 mmol) and triethylamine was added (1.38 ml, 9.83 mmol) in N,N-dimethylformamide (10.0 ml). After stirring for another 2 hours at room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried (Na ₂ SO ₄ ) and concentrated under reduced pressure. The residue was purified by silica gel chromatography using hexanes/ethyl acetate as the eluent to give the title compound as a white solid (1.30 g, 43% yield).

^1H NMR (CDCl3): 8.87 (m, 1H), 8.78 (m, 1H), 8.08 (d, 1H), 7.67 (m, 2H), 7.63 (d, 2H ), 7.52 (d, 1H), 4.27 (d, 1H), 4.02 (s, 3H), 3.89 (d, 1H).

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Step B. Preparation of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]1-naphthalenecarboxylic acid.

To a stirred solution of methyl 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5(trifluoromethyl)-3-isoxazolyl]-1-naphthalene-carboxylate (i.e. the product From step A) (1.20 g, 2.47 mmol) in tetrahydrofuran (10 ml), a solution of lithium hydroxide monohydrate (0.31 g, 7.41 mmol) in water (10 ml) was added. The resulting mixture was stirred overnight at room temperature. The reaction mixture was partitioned between water and diethyl ether. The aqueous layer was then acidified with 6 N aqueous hydrochloric acid to pH 2 and extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated to give the title compound as a white solid (1.10 g, 94% yield).

1H NMR (DMSO-d6): 13.52 (br.s, 1H), 8.83 (m, 1H), 8.77 (m, 1H), 8.12 (d, 1H), 7.92 ( d, 1H), 7.88 (d, 2H), 7.73 (m, 2H), 4.56 (s, 2H).

Step C. Preparation of N-[(1R)-2-amino-1-methyl-2-exoethyl]-4-[5-(3,5-dichloro-4-fluorophenyl)-4,5dihydro-5-(trifluoromethyl) -3-isoxazolyl]-1-naphthalenecarboxamide.

A mixture of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1naphthalenecarboxylic acid (i.e. the product from step B) ( 190 mg, 0.40 mmol), (R)-2-aminopropanamide hydrochloride (97 mg, 0.80 mmol), triethylamine (0.17 ml, 1.20 mmol) and 1-[bis(dimethylamino)methylene-1H1 ,2,3-triazolo[4,5-b]pyridinium hexafluorophosphate 3-oxide (HATU, 182 mg, 0.48 mmol) in DMF (3 ml) was stirred at room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and water, the phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated. The resulting residue was purified by silica gel column chromatography using hexanes/ethyl acetate as the eluent to obtain the title product, the compound of the present invention, as a white solid (180 mg, 83% yield).

1H NMR (DMSO-d6): 8.77 (d, 1H), 8.72 (d, 1H), 8.30 (d, 1H), 7.88 (m, 3H), 7.63-7. 72 (m, 3H), 7.46 (br.s, 1H), 7.05 (br.s, 1H), 4.54 (s, 2H), 4.50 (m, 1H), 1.36 (d, 3H).

Synthesis example 2.

Preparation of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-(2pyridinylmethyl)-1-naphthalene-carboxamide (compound 15) .

4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylic acid mixture (200 mg, 0.42 mmol), 2 -pyridylmethanamine (92 mg, 0.84 mmol), triethylamine (0.18 ml, 1.26 mmol) and 1-[bis(dimethylamino)methylene-1H-1,2,3-triazolo[4,5-b] Pyridinium hexafluorophosphate 3-oxide (HATU, 240 mg, 0.64 mmol) in DMF (3 ml) was stirred at room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and water. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated. The resulting residue was purified by silica gel column chromatography using hexanes/ethyl acetate as the eluent to give the title product, the compound of the present invention, as a white solid (132 mg, 56% yield).

1H NMR ( _CDCl3 ): 8.80 (d, 1H), 8.50 (d, 1H), 8.36 (d, 1H), 7.71 (ddd, 1H), 7.58-7.66 (m, 5H), 7.49 (s, 1H), 7.48 (s, 1H), 7.36 (d, 1H), 7.22 (dd, 1H), 4.84 (d, 2H) , 4.25 (d, 1H), 3.89 (d, 1H).

Synthesis example 3.

Preparation of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(tri-fluoromethyl)-3-isoxazolyl]-N[(methoxyimino)methyl]-1-naphthalene-carboxamide (compound 33).

Step A. Preparation of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]1-naphthalenecarboxamide.

To a suspension of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1naphthalenecarboxylic acid (500 mg, 1.06 mmol) in dichloromethane ( 20 ml), oxalyl chloride (269 mg, 2.12 mmol) and 1 drop of DMF were added. The mixture was stirred at room temperature for 1 hour, then concentrated and distilled off with toluene under reduced pressure. The residue was dissolved in THF (5 ml) and aqueous ammonium hydroxide (3 ml, 14.8 M) was added. The reaction mixture was stirred at room temperature for 4 hours and then partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated to give the primary amide as a white solid (490 mg). The crude amide was used directly in the next step without further purification.

Step B. Preparation of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]N-[(methoxyimino)methyl]-1-naphthalenecarboxamide.

Mixture of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1naphthalenecarboxamide (490 mg), methoxyamine hydrochloride (266 mg, 3 .18 mmol) and triethylorthoformate (2 ml, 12 mmol) in toluene (20 ml) were stirred at 70°C for 24 hours. The reaction mixture was cooled and partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried, concentrated and the residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to give the title product, the compound of the present invention, as a white solid (402 mg, 72 % yield in two stages).

^1H NMR ( _CDCl3 ): 8.83 (d, 1H), 8.66 (d, 1H), 8.34 (d, 1H), 7.89 (d, 1H), 7.69 (m, 3H), 7.64 (d, 2H), 7.54 (d, 1H), 4.27 (d, 1H), 3.90 (d, 1H), 3.89 (s, 3H).

Synthesis example 4.

Preparation of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(tri-fluoromethyl)-3-isoxazolyl]-N-(2pyridinylmethyl)-N-[(4R)- 2-ethyl-3-oxo-4-isoazolidinyl]-1-naphthalenecarboxamide (compound 34).

To a suspension of 4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1naphthalenecarboxylic acid (200 mg, 0.42 mmol) in dichloromethane ( 10 ml) oxalyl chloride (107 mg, 0.84 mmol) and 1 drop of DMF were added. The mixture was stirred at room temperature for 1 hour, then concentrated and distilled off with toluene under reduced pressure. The residue was dissolved in 2 ml of dichloromethane and added slowly to a suspension of (4R)-4-amino-2-ethylisoxazolidin-3-one hydrochloride (210 mg, 1.26 mmol) and triethylamine (170 mg, 1.68 mmol) in dichloromethane ( 5 ml) at room temperature. The reaction mixture was stirred at room temperature overnight, then concentrated and the residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to give the title compound as a white solid (196 mg, 79% yield).

^1H NMR ( _CDCl3 ): 8.81 (d, 1H), 8.30 (d, 1H), 7.60-7.67 (m, 5H), 7.45 (d, 1H), 6. 85 (br.s, 1H), 5.00 (m, 2H), 4.26 (d, 1H), 4.13 (dd, 1H), 3.89 (d, 1H), 3.65 (m , 2H), 1.26 (t, 3H).

Synthesis example 5.

Preparation of N[[4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3isoxazolyl]-1-naphthalenyl]carbonyl]glycine methyl ester (compound 35).

Step A. Preparation of 3-(4-bromo-1-naphthalenyl)-5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5(trifluoromethyl)isoxazole.

N-chlorosuccinimide (0.64 g, 4.8 mmol) was added to a stirred solution of 4-bromo-1-naphthalene carboxylate oxime (1.00 g, 4.0 mmol) in N,N-dimethylformamide (12.0 mL). The reaction mixture was stirred for 1 hour at room temperature and then a solution of 1,3-dichloro-4-fluoro-5[1-(trifluoromethyl)ethenyl]benzene (1.24 g, 4.8 mmol) and triethylamine (1 .68 ml, 12.0 mmol) in N,N-dimethylformamide (12.0 ml). After stirring for another 2 hours at room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried (Na ₂ SO ₄ ) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using hexanes/ethyl acetate as the eluent to give the title compound as a white solid (1.60 g, 76% yield).

1H NMR (CDCl3): 8.88 (m, 1H), 8.35 (m, 1H), 7.82 (d, 1H), 7.69 (m, 2H), 7.64 (d, 2H) , 7.36 (d, 1H), 4.27 (d, 1H), 3.88 (d, 1H).

Step B. Preparation of N-[[4-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5(trifluoromethyl)-3-isoxazolyl]-1-naphthalenyl]carbonyl]- methyl ester glycine.

A mixture of 3-(4-bromo-1-naphthalenyl)-5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole (1000 mg, 1.97 mmol), [ 1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(P) (PdCl ₂ (dppf)) (146 mg, 0.20 mmol), glycine methyl ester hydrochloride (371 mg, 2.96 mmol) and triethylamine (2 .76 ml, 19.7 mmol) in toluene (20 ml) was purged with carbon monoxide for 15 min. The reaction mixture was stirred at 70°C under an atmosphere of carbon monoxide overnight. The mixture was cooled to room temperature, filtered through a short layer of Celite®, a diatomaceous earth filter powder, and rinsed with a small amount of ethyl acetate. The filtrate was concentrated and the residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to give the title product, the compound of the present invention, as a white solid (600 mg, 56% yield).

^1H NMR (DMSO-d6): 9.13 (t, 1H), 8.78 (d, 1H), 8.32 (d, 1H), 7.90 (m, 3H), 7.70 (m , 3H), 4.53 (s, 2H), 4.11 (d, 2H), 4.74 (s, 3H).

The above Synthesis Example 1 is an example of the preparation of a compound of Formula 1 wherein J is J-1.

Synthesis Example 2 above is an example of the preparation of a compound of formula 1 wherein J is J-2.

Synthesis Example 3 above is an example of the preparation of a compound of Formula 1 wherein J is J-3.

Synthesis Example 4 above is an example of the preparation of a compound of Formula 1 wherein J is J-4.

Synthesis Example 5 above is an example of the preparation of a compound of formula 1 wherein J is J-5.

Compounds of formula 1, where J is J-6, can be prepared using techniques

- 20 043836 similar to the methods described above in synthesis examples 1, 2, 4 and 5.

Compounds of formula 1, wherein J is (i) C ₂ -C ₄ alkyl substituted with one cyano group;

(ii) -CH ₂ (cyclopropyl) substituted with one cyano group; or (iii) cyclopropyl, unsubstituted or substituted with one cyano group or one C(O)NHR ¹⁷ group, can be prepared using procedures similar to those described above in Synthetic Examples 1, 2, 4 and 5.

Using the methods described in the invention, together with well-known methods, the compounds listed below in the table can be obtained. 1-1-7-2. The following tables use abbreviations to indicate the following: Me is methyl, Et is ethyl, i-Pr is isopropyl, i-Bu is isobutyl and OMe is methoxy.

Table 1-1

ABOUT- ~n g |] ^R1 b Ί 1 X I J Γιϊ I II xx n, A. Zh ⁴ Ria GT ΊΓ Ν II * । O R ² R ³

Ria Rib R2 R3 R4 Ria Rib R2 R3 R4 Cl Cl Me H H CF3 H Me H H Cl Cl Cl H Me CF3 H Me H Me Cl Cl Me H Et CF3 H Me H Et Cl Cl Me H i-Pr CF3 H Me H i-Pr Cl Cl Me H CH2CF3 CF3 H Me H CH2CF3 Cl Cl Me Me H CF3 H Me Me H Cl Cl Me Me Me CF3 H Me Me Me Cl Cl Me Me Et CF3 H Me Me Et Cl Cl Me Me i-Pr CF3 H Me Me i-Pr Cl Cl Me Me CH2CF3 CF3 H Me Me CH2CF3 Cl Cl Et H H CF3 H Et H H Cl Cl Et H Me CF3 H Et H Me Cl Cl Et H Et CF3 H Et H Et Cl Cl Et H i-Pr CF3 H Et H i-Pr Cl Cl Et H CH2CF3 CF3 H Et H CH2CF3 Cl Cl Et Me H CF3 H Et Me H Cl Cl Et Me Me CF3 H Et Me Me Cl Cl Et Me Et CF3 H Et Me Et Cl Cl Et Me i-Pr CF3 H Et Me i-Pr Cl Cl Et Me CH2CF3 CF3 H Et Me CH2CF3 Cl Cl i-Pr H H CF3 H i-Pr H H Cl Cl i-Pr H Me CF3 H i-Pr H Me

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Cl Cl i-Pr H Et CF3 H i-Pr H Et Cl Cl i-Pr H i-Pr CF3 H i-Pr H i-Pr Cl Cl i-Pr H CH2CF3 CF3 H i-Pr H CH2CF3 Cl Cl i-Pr Me H CF3 H i-Pr Me H Cl Cl i-Pr Me Me CF3 H i-Pr Me Me Cl Cl i-Pr Me Et CF3 H i-Pr Me Et Cl Cl i-Pr Me i-Pr CF3 H i-Pr Me i-Pr Cl Cl i-Pr Me CH2CF3 CF3 H i-Pr Me CH2CF3 Cl Cl iBu H H CF3 H iBu H H Cl Cl iBu H Me CF3 H iBu H Me Cl Cl iBu H Et CF3 H iBu H Et Cl Cl iBu H i-Pr CF3 H iBu H i-Pr Cl Cl iBu H CH2CF3 CF3 H iBu H CH2CF3 Cl Cl iBu Me H CF3 H iBu Me H Cl Cl iBu Me Me CF3 H iBu Me Me Cl Cl iBu Me Et CF3 H iBu Me Et Cl Cl iBu Me i-Pr CF3 H iBu Me i-Pr Cl Cl iBu Me CH2CF3 CF3 H iBu Me CH2CF3 Cl Cl CH2OH H H CF3 H CH2OH H H Cl Cl CH2OH H Me CF3 H CH2OH H Me Cl Cl CH2OH H Et CF3 H CH2OH H Et Cl Cl CH2OH H i-Pr CF3 H CH2OH H i-Pr Cl Cl CH2OH H CH2CF3 CF3 H CH2OH H CH2CF3 Cl Cl CH2OH Me H CF3 H CH2OH Me H Cl Cl CH2OH Me Me CF3 H CH2OH Me Me Cl Cl CH2OH Me Et CF3 H CH2OH Me Et Cl Cl CH2OH Me i-Pr CF3 H CH2OH Me i-Pr Cl Cl CH2OH Me CH2CF3 CF3 H CH2OH Me CH2CF3 Cl Cl CH2OM e H H CF3 H CH2OM e H H Cl Cl CH2OM e H Me CF3 H CH2OM e H Me Cl Cl CH2OM e H Et CF3 H CH2OM e H Et

- 22 043836

Cl Cl CH2OM e H i-Pr CF3 H CH2OM e H i-Pr Cl Cl CH2OM e H CH2CF3 CF3 H CH2OM e H CH2CF3 Cl Cl CH2OM e Me H CF3 H CH2OM e Me H Cl Cl CH2OM e Me Me CF3 H CH2OM e Me Me Cl Cl CH2OM e Me Et CF3 H CH2OM e Me Et Cl Cl CH2OM e Me i-Pr CF3 H CH2OM e Me i-Pr Cl Cl CH2OM e Me CH2CF3 CF3 H CH2OM e Me CH2CF3 CF3 Cl Me H H CF3 Cl iBu H H CF3 Cl Me H Me CF3 Cl iBu H Me CF3 Cl Me H Et CF3 Cl iBu H Et CF3 Cl Me H i-Pr CF3 Cl iBu H i-Pr CF3 Cl Me H CH2CF3 CF3 Cl iBu H CH2CF3 CF3 Cl Me Me H CF3 Cl iBu Me H CF3 Cl Me Me Me CF3 Cl iBu Me Me CF3 Cl Me Me Et CF3 Cl iBu Me Et CF3 Cl Me Me i-Pr CF3 Cl iBu Me i-Pr CF3 Cl Me Me CH2CF3 CF3 Cl iBu Me CH2CF3 CF3 Cl Et H H CF3 Cl CH2OH H H CF3 Cl Et H Me CF3 Cl CH2OH H Me CF3 Cl Et H Et CF3 Cl CH2OH H Et CF3 Cl Et H i-Pr CF3 Cl CH2OH H i-Pr CF3 Cl Et H CH2CF3 CF3 Cl CH2OH H CH2CF3 CF3 Cl Et Me H CF3 Cl CH2OH Me H CF3 Cl Et Me Me CF3 Cl CH2OH Me Me CF3 Cl Et Me Et CF3 Cl CH2OH Me Et CF3 Cl Et Me i-Pr CF3 Cl CH2OH Me i-Pr CF3 Cl Et Me CH2CF3 CF3 Cl CH2OH Me CH2CF3

- 23 043836

CF3 Cl i-Pr H H CF3 Cl CH2OM e H H CF3 Cl i-Pr H Me CF3 Cl CH2OM e H Me CF3 Cl i-Pr H Et CF3 Cl CH2OM e H Et CF3 Cl i-Pr H i-Pr CF3 Cl CH2OM e H i-Pr CF3 Cl i-Pr H CH2CF3 CF3 Cl CH2OM e H CH2CF3 CF3 Cl i-Pr Me H CF3 Cl CH2OM e Me H CF3 Cl i-Pr Me Me CF3 Cl CH2OM e Me Me CF3 Cl i-Pr Me Et CF3 Cl CH2OM e Me Et CF3 Cl i-Pr Me i-Pr CF3 Cl CH2OM e Me i-Pr CF3 Cl i-Pr Me CH2CF3 CF3 Cl CH2OM e Me CH2CF3

Table 1-2

Ria Rib R2 R3 R4 Ria Rib R2 R3 R4 Cl Cl Me H H CF3 H Me H H Cl Cl Cl H Me CF3 H Me H Me Cl Cl Me H Et CF3 H Me H Et Cl Cl Me H i-Pr CF3 H Me H i-Pr Cl Cl Me H CH2CF3 CF3 H Me H CH2CF3 Cl Cl Me Me H CF3 H Me Me H Cl Cl Me Me Me CF3 H Me Me Me

- 24 043836

Cl Cl Me Me Et CF3 H Me Me Et Cl Cl Me Me i-Pr CF3 H Me Me i-Pr Cl Cl Me Me CH2CF3 CF3 H Me Me CH2CF3 Cl Cl Et H H CF3 H Et H H Cl Cl Et H Me CF3 H Et H Me Cl Cl Et H Et CF3 H Et H Et Cl Cl Et H i-Pr CF3 H Et H i-Pr Cl Cl Et H CH2CF3 CF3 H Et H CH2CF3 Cl Cl Et Me H CF3 H Et Me H Cl Cl Et Me Me CF3 H Et Me Me Cl Cl Et Me Et CF3 H Et Me Et Cl Cl Et Me i-Pr CF3 H Et Me i-Pr Cl Cl Et Me CH2CF3 CF3 H Et Me CH2CF3 Cl Cl i-Pr H H CF3 H i-Pr H H Cl Cl i-Pr H Me CF3 H i-Pr H Me Cl Cl i-Pr H Et CF3 H i-Pr H Et Cl Cl i-Pr H i-Pr CF3 H i-Pr H i-Pr Cl Cl i-Pr H CH2CF3 CF3 H i-Pr H CH2CF3 Cl Cl i-Pr Me H CF3 H i-Pr Me H Cl Cl i-Pr Me Me CF3 H i-Pr Me Me Cl Cl i-Pr Me Et CF3 H i-Pr Me Et Cl Cl i-Pr Me i-Pr CF3 H i-Pr Me i-Pr Cl Cl i-Pr Me CH2CF3 CF3 H i-Pr Me CH2CF3 Cl Cl iBu H H CF3 H iBu H H Cl Cl iBu H Me CF3 H iBu H Me Cl Cl iBu H Et CF3 H iBu H Et Cl Cl iBu H i-Pr CF3 H iBu H i-Pr Cl Cl iBu H CH2CF3 CF3 H iBu H CH2CF3 Cl Cl iBu Me H CF3 H iBu Me H Cl Cl iBu Me Me CF3 H iBu Me Me Cl Cl iBu Me Et CF3 H iBu Me Et Cl Cl iBu Me i-Pr CF3 H iBu Me i-Pr Cl Cl iBu Me CH2CF3 CF3 H iBu Me CH2CF3 Cl Cl CH2OH H H CF3 H CH2OH H H

- 25 043836

Cl Cl CH2OH H Me CF3 H CH2OH H Me Cl Cl CH2OH H Et CF3 H CH2OH H Et Cl Cl CH2OH H i-Pr CF3 H CH2OH H i-Pr Cl Cl CH2OH H CH2CF3 CF3 H CH2OH H CH2CF3 Cl Cl CH2OH Me H CF3 H CH2OH Me H Cl Cl CH2OH Me Me CF3 H CH2OH Me Me Cl Cl CH2OH Me Et CF3 H CH2OH Me Et Cl Cl CH2OH Me i-Pr CF3 H CH2OH Me i-Pr Cl Cl CH2OH Me CH2CF3 CF3 H CH2OH Me CH2CF3 Cl Cl CH2OM e H H CF3 H CH2OM e H H Cl Cl CH2OM e H Me CF3 H CH2OM e H Me Cl Cl CH2OM e H Et CF3 H CH2OM e H Et Cl Cl CH2OM e H i-Pr CF3 H CH2OM e H i-Pr Cl Cl CH2OM e H CH2CF3 CF3 H CH2OM e H CH2CF3 Cl Cl CH2OM e Me H CF3 H CH2OM e Me H Cl Cl CH2OM e Me Me CF3 H CH2OM e Me Me Cl Cl CH2OM e Me Et CF3 H CH2OM e Me Et Cl Cl CH2OM e Me i-Pr CF3 H CH2OM e Me i-Pr Cl Cl CH2OM e Me CH2CF3 CF3 H CH2OM e Me CH2CF3 CF3 Cl Me H H CF3 Cl iBu H H CF3 Cl Me H Me CF3 Cl iBu H Me CF3 Cl Me H Et CF3 Cl iBu H Et CF3 Cl Me H i-Pr CF3 Cl iBu H i-Pr CF3 Cl Me H CH2CF3 CF3 Cl iBu H CH2CF3

- 26 043836

CF3 Cl Me Me H CF3 Cl iBu Me H CF3 Cl Me Me Me CF3 Cl iBu Me Me CF3 Cl Me Me Et CF3 Cl iBu Me Et CF3 Cl Me Me i-Pr CF3 Cl iBu Me i-Pr CF3 Cl Me Me CH2CF3 CF3 Cl iBu Me CH2CF3 CF3 Cl Et H H CF3 Cl CH2OH H H CF3 Cl Et H Me CF3 Cl CH2OH H Me CF3 Cl Et H Et CF3 Cl CH2OH H Et CF3 Cl Et H i-Pr CF3 Cl CH2OH H i-Pr CF3 Cl Et H CH2CF3 CF3 Cl CH2OH H CH2CF3 CF3 Cl Et Me H CF3 Cl CH2OH Me H CF3 Cl Et Me Me CF3 Cl CH2OH Me Me CF3 Cl Et Me Et CF3 Cl CH2OH Me Et CF3 Cl Et Me i-Pr CF3 Cl CH2OH Me i-Pr CF3 Cl Et Me CH2CF3 CF3 Cl CH2OH Me CH2CF3 CF3 Cl i-Pr H H CF3 Cl CH2OM e H H CF3 Cl i-Pr H Me CF3 Cl CH2OM e H Me CF3 Cl i-Pr H Et CF3 Cl CH2OM e H Et CF3 Cl i-Pr H i-Pr CF3 Cl CH2OM e H i-Pr CF3 Cl i-Pr H CH2CF3 CF3 Cl CH2OM e H CH2CF3 CF3 Cl i-Pr Me H CF3 Cl CH2OM e Me H CF3 Cl i-Pr Me Me CF3 Cl CH2OM e Me Me CF3 Cl i-Pr Me Et CF3 Cl CH2OM e Me Et CF3 Cl i-Pr Me i-Pr CF3 Cl CH2OM e Me i-Pr CF3 Cl i-Pr Me CH2CF3 CF3 Cl CH2OM e Me CH2CF3

- 27 043836

Table 2-1

R ^1a is Cl, R ^1b is Cl, R ⁵ is H.

Ω Ω Q Ώ 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 28 043836

R ^1a is CF ₃ , R ^1b is H, R ⁵ is H.

Q Q 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl 1-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1-Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

R ^1a is CF ₃ , R ^1b is Cl, R ⁵ is H.

Q 2 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl

- 29 043836

l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

R ^1a is Cl, R ^1b is Cl, R ⁵ is Me.

Q Q Q Q 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1-Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxadiazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiad iazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 30 043836

R ^la represents CF ₃ , R ^lb represents Η, R ⁵ represents Me.

Ω Ω Q Ώ 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1-Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

R ^la is CF ₃ , R ^lb is Cl, R ⁵ is Me.

2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl

-31 043836

5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

Table 2-2

R ^1a is Cl, R ^1b is Cl, R ⁵ is Me.

Q Q Q Ώ 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-tr iazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1-Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 32 043836

R ^1a represents CF ₃ , R ^1b represents H, R ⁵ represents Me.

Q Q Ώ Q 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imide azolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl)

2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4- triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5 -(tetra azolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 33 043836

R ^la is CF ₃ , R ^lb is Cl, R ⁵ is Me.

Ω Ω Ω Ω 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl)

3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

-34043836

Table 2-3

R ^1a is Cl, R ^1b is Cl, R ⁵ is H.

Ω Ω Ώ 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl l-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 35 043836

R ^1a is CF ₃ , R ^1b is H, R ⁵ is H.

2 Q 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyr ide azinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

R ^1a is CF ₃ , R ^1b is Cl, R ⁵ is H.

Q 2 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl l-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl

- 36 043836

l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1-Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

R ^1a is Cl, R ^1b is Cl, R ⁵ is Me.

2 2 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl 1-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxadiazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 37 043836

R ^la represents CF ₃ , R ^lb represents Η, R ⁵ represents Me.

2 2 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl l-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

R ^la is CF ₃ , R ^lb is Cl, R ⁵ is Me.

2 2 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl l-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl)

-38 043836

5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiad iazolyl

Table 2-4

R ^1a is Cl, R ^1b is Cl, R ⁵ is Me.

Q Q Q Q 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl 1-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imidazolyl 1-Me-4-imidazolyl l-Me-5-imidazolyl 1,2,3-tr iazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 39 043836

R ^1a represents CF ₃ , R ^1b represents H, R ⁵ represents Me.

2 2 2 2 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imide azolyl 1-Me-4-imidazolyl 1 -Me- 5 -imide az ol yl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl)

2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4- triazolyl) tetrazolyl 1 -Me-5-(tetrazolyl) 2-Me-5-(tetra azolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxad iazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

- 40 043836

R ^1a represents CF ₃ , R ^1b represents Cl, R ⁵ represents Me.

Ω Ω Ω Q 2-pyridinyl 3-pyridinyl 4-pyridinyl 2-pyrimidinyl 4-pyrimidinyl 5-pyrimidinyl 2-pyrazinyl 3-pyrazinyl 3-pyridazinyl 4-pyridazinyl 3 -(1,2,4-triazinyl) 5-(1,2,4-triazinyl) 6-(1,2,4-triazinyl) 2-(1,3,5-triazinyl) 2-furanyl 3-furanyl 2-thienyl 3-thienyl 2-pyrrolyl 3-pyrrolyl 1-Me-2-pyrrolyl 1-Me-3-pyrrolyl 3-pyrazolyl 4-pyrazolyl 5-pyrazolyl 1-Me-3-pyrazolyl 1-Me-4-pyrazolyl l-Me-5-pyrazolyl 2-imidazolyl 4-imidazolyl 1-Me-2-imide azolyl 1-Me-4-imidazolyl 1 -Me- 5 -imide az ol yl 1,2,3-triazolyl 1-Me-4-(1,2,3triazolyl) 1-Me-5-(1,2,3triazolyl) 1,2,4-triazolyl 1-Me-3-(1,2,4triazolyl) 1-Me-5-(1,2,4triazolyl) 2-Me-3-(1,2,4triazolyl) 2-Me-5-(1,2,4triazolyl) 4-Me-3-(1,2,4triazolyl) tetra azolyl 1 -Me-5-(tetra azolyl) 2-Me-5-(tetrazolyl) 2-oxazolyl 4-oxazolyl 5-oxazolyl 2-thiazolyl 4-thiazolyl 5-thiazolyl 3-isoxazolyl 4-isoxazolyl 5-isoxazolyl 3-isothiazolyl 4-isothiazolyl 5-isothiazolyl 4-(1,2,3oxadiazolyl) 5-(1,2,3oxadiazolyl) 3-(1,2,4oxadiazolyl) 5-(1,2,4oxadiazolyl) 1,3,4-oxadiazolyl 4-(1,2,3thiadiazolyl) 5-(1,2,3thiadiazolyl) 3-(1,2,4thiadiazolyl) 5-(1,2,4thiadiazolyl) 1,3,4-thiadiazolyl

Table 3-1

F

R

Ria Rib R6 R7 Ria Rib R6 R7 Cl Cl H Me CF3 H H Me Cl Cl H Et CF3 H H Et Cl Cl Me Me CF3 H Me Me Cl Cl Me Et CF3 H Me Et CF3 Cl H Me CF3 Cl Me Me CF3 Cl H Et CF3 Cl Me Et

- 41 043836

Table 3-2

Ria Rib R6 R7 Ria Rib R6 R7 Cl Cl H Me CF3 H H Me Cl Cl H Et CF3 H H Et Cl Cl Me Me CF3 H Me Me Cl Cl Me Et CF3 H Me Et CF3 Cl H Me CF3 Cl Me Me CF3 Cl H Et CF3 Cl Me Et

Table 4-1

X represents -O-.

Ria Rib R8 Ria Rib R8 Cl Cl Me CF3 H Me Cl Cl Et CF3 H Et Cl Cl CH2CF3 CF3 H CH2CF3 CF3 Cl Me CF3 Cl Et CF3 Cl CH2CF3

X represents -C(O)-.

Ria Rib R8 Ria Rib R8 Cl Cl Me CF3 H Me Cl Cl Et CF3 H Et Cl Cl CH2CF3 CF3 H CH2CF3 CF3 Cl Me CF3 Cl Et CF3 Cl CH2CF3

- 42 043836

Table 4-2

X represents -O-. Ria Rib R8 Ria Rib R8 Cl Cl Me CF3 H Me Cl Cl Et CF3 H Et Cl Cl CH2CF3 CF3 H CH2CF3 CF3 Cl Me CF3 Cl Et CF3 Cl CH2CF3

X represents -C(O)-.

Ria Rib R8 Ria Rib R8 Cl Cl Me CF3 H Me Cl Cl Et CF3 H Et Cl Cl CH2CF3 CF3 H CH2CF3 CF3 Cl Me CF3 Cl Et CF3 Cl CH2CF3

Table 5-1

Ria Rib R14 R15 Ria Rib R14 R15 Cl Cl Me H CF3 H Me H Cl Cl Et H CF3 H Et H Cl Cl i-Pr H CF3 H i-Pr H Cl Cl iBu H CF3 H iBu H Cl Cl CH2OH H CF3 H CH2OH H Cl Cl CH20M e H CF3 H CH20M e H Cl Cl Me Me CF3 H Me Me Cl Cl Et Me CF3 H Et Me Cl Cl i-Pr Me CF3 H i-Pr Me Cl Cl iBu Me CF3 H iBu Me Cl Cl CH2OH Me CF3 H CH2OH Me Cl Cl CH20M e Me CF3 H CH20M e Me Cl Cl Me Et CF3 H Me Et Cl Cl Et Et CF3 H Et Et

- 43 043836

Cl Cl i-Pr Et CF3 H i-Pr Et Cl Cl iBu Et CF3 H iBu Et Cl Cl CH2OH Et CF3 H CH2OH Et Cl Cl CH2OM e Et CF3 H CH2OM e Et Cl Cl Me i-Pr CF3 H Me i-Pr Cl Cl Et i-Pr CF3 H Et i-Pr Cl Cl i-Pr i-Pr CF3 H i-Pr i-Pr Cl Cl iBu i-Pr CF3 H iBu i-Pr Cl Cl CH2OH i-Pr CF3 H CH2OH i-Pr Cl Cl CH2OM e i-Pr CF3 H CH2OM e i-Pr Cl Cl Me CH2CF3 CF3 H Me CH2CF3 Cl Cl Et CH2CF3 CF3 H Et CH2CF3 Cl Cl i-Pr CH2CF3 CF3 H i-Pr CH2CF3 Cl Cl iBu CH2CF3 CF3 H iBu CH2CF3 Cl Cl CH2OH CH2CF3 CF3 H CH2OH CH2CF3 Cl Cl CH2OM e CH2CF3 CF3 H CH2OM e CH2CF3 CF3 Cl Me H CF3 Cl Me i-Pr CF3 Cl Et H CF3 Cl Et i-Pr CF3 Cl i-Pr H CF3 Cl i-Pr i-Pr CF3 Cl iBu H CF3 Cl iBu i-Pr CF3 Cl CH2OH H CF3 Cl CH2OH i-Pr CF3 Cl CH2OM e H CF3 Cl CH2OM e i-Pr CF3 Cl Me Me CF3 Cl Me CH2CF3 CF3 Cl Et Me CF3 Cl Et CH2CF3 CF3 Cl i-Pr Me CF3 Cl i-Pr CH2CF3 CF3 Cl iBu Me CF3 Cl iBu CH2CF3 CF3 Cl CH2OH Me CF3 Cl CH2OH CH2CF3 CF3 Cl CH2OM e Me CF3 Cl CH2OM e CH2CF3 CF3 Cl Me Et

CF3 Cl Et Et CF3 Cl i-Pr Et CF3 Cl iBu Et CF3 Cl CH2OH Et CF3 Cl CH2OM e Et

- 44 043836

Table 5-2

Ria Rib R14 R15 Ria Rib R14 R15 Cl Cl Me H CF3 H Me H Cl Cl Et H CF3 H Et H Cl Cl i-Pr H CF3 H i-Pr H Cl Cl iBu H CF3 H iBu H Cl Cl CH2OH H CF3 H CH2OH H Cl Cl CH2OM e H CF3 H CH2OM e H Cl Cl Me Me CF3 H Me Me Cl Cl Et Me CF3 H Et Me Cl Cl i-Pr Me CF3 H i-Pr Me Cl Cl iBu Me CF3 H iBu Me Cl Cl CH2OH Me CF3 H CH2OH Me Cl Cl CH2OM e Me CF3 H CH2OM e Me Cl Cl Me Et CF3 H Me Et Cl Cl Et Et CF3 H Et Et Cl Cl i-Pr Et CF3 H i-Pr Et Cl Cl iBu Et CF3 H iBu Et Cl Cl CH2OH Et CF3 H CH2OH Et

- 45 043836

Cl Cl CH2OM e Et CF3 H CH2OM e Et Cl Cl Me i-Pr CF3 H Me i-Pr Cl Cl Et i-Pr CF3 H Et i-Pr Cl Cl i-Pr i-Pr CF3 H i-Pr i-Pr Cl Cl iBu i-Pr CF3 H iBu i-Pr Cl Cl CH2OH i-Pr CF3 H CH2OH i-Pr Cl Cl CH2OM e i-Pr CF3 H CH2OM e i-Pr Cl Cl Me CH2CF3 CF3 H Me CH2CF3 Cl Cl Et CH2CF3 CF3 H Et CH2CF3 Cl Cl i-Pr CH2CF3 CF3 H i-Pr CH2CF3 Cl Cl iBu CH2CF3 CF3 H iBu CH2CF3 Cl Cl CH2OH CH2CF3 CF3 H CH2OH CH2CF3 Cl Cl CH2OM e CH2CF3 CF3 H CH2OM e CH2CF3 CF3 Cl Me H CF3 Cl Me i-Pr CF3 Cl Et H CF3 Cl Et i-Pr CF3 Cl i-Pr H CF3 Cl i-Pr i-Pr CF3 Cl iBu H CF3 Cl iBu i-Pr CF3 Cl CH2OH H CF3 Cl CH2OH i-Pr CF3 Cl CH2OM e H CF3 Cl CH2OM e i-Pr CF3 Cl Me Me CF3 Cl Me CH2CF3 CF3 Cl Et Me CF3 Cl Et CH2CF3 CF3 Cl i-Pr Me CF3 Cl i-Pr CH2CF3 CF3 Cl iBu Me CF3 Cl iBu CH2CF3 CF3 Cl CH2OH Me CF3 Cl CH2OH CH2CF3 CF3 Cl CH2OM e Me CF3 Cl CH2OM e CH2CF3 CF3 Cl Me Et CF3 Cl Et Et CF3 Cl i-Pr Et CF3 Cl iBu Et CF3 Cl CH2OH Et CF3 Cl CH2OM e Et

- 46 043836

Table 5-3

Rla Rib R14 R15 Rla Rib R14 R15 Cl Cl Me H CF3 H Me H Cl Cl Et H CF3 H Et H Cl Cl i-Pr H CF3 H i-Pr H Cl Cl iBu H CF3 H iBu H Cl Cl CH2OH H CF3 H CH2OH H Cl Cl CH2OM e H CF3 H CH2OM e H Cl Cl Me Me CF3 H Me Me Cl Cl Et Me CF3 H Et Me Cl Cl i-Pr Me CF3 H i-Pr Me Cl Cl iBu Me CF3 H iBu Me Cl Cl CH2OH Me CF3 H CH2OH Me Cl Cl CH2OM e Me CF3 H CH2OM e Me Cl Cl Me Et CF3 H Me Et Cl Cl Et Et CF3 H Et Et Cl Cl i-Pr Et CF3 H i-Pr Et Cl Cl iBu Et CF3 H iBu Et Cl Cl CH2OH Et CF3 H CH2OH Et Cl Cl CH2OM e Et CF3 H CH2OM e Et Cl Cl Me i-Pr CF3 H Me i-Pr Cl Cl Et i-Pr CF3 H Et i-Pr Cl Cl i-Pr i-Pr CF3 H i-Pr i-Pr

- 47 043836

Cl Cl iBu i-Pr CF3 H iBu i-Pr Cl Cl CH2OH i-Pr CF3 H CH2OH i-Pr Cl Cl CH2OM e i-Pr CF3 H CH2OM e i-Pr Cl Cl Me CH2CF3 CF3 H Me CH2CF3 Cl Cl Et CH2CF3 CF3 H Et CH2CF3 Cl Cl i-Pr CH2CF3 CF3 H i-Pr CH2CF3 Cl Cl iBu CH2CF3 CF3 H iBu CH2CF3 Cl Cl CH2OH CH2CF3 CF3 H CH2OH CH2CF3 Cl Cl CH2OM e CH2CF3 CF3 H CH2OM e CH2CF3 CF3 Cl Me H CF3 Cl Me i-Pr CF3 Cl Et H CF3 Cl Et i-Pr CF3 Cl i-Pr H CF3 Cl i-Pr i-Pr CF3 Cl iBu H CF3 Cl iBu i-Pr CF3 Cl CH2OH H CF3 Cl CH2OH i-Pr CF3 Cl CH2OM e H CF3 Cl CH2OM e i-Pr CF3 Cl Me Me CF3 Cl Me CH2CF3 CF3 Cl Et Me CF3 Cl Et CH2CF3 CF3 Cl i-Pr Me CF3 Cl i-Pr CH2CF3 CF3 Cl iBu Me CF3 Cl iBu CH2CF3 CF3 Cl CH2OH Me CF3 Cl CH2OH CH2CF3 CF3 Cl CH2OM e Me CF3 Cl CH2OM e CH2CF3 CF3 Cl Me Et CF3 Cl Et Et CF3 Cl i-Pr Et CF3 Cl iBu Et CF3 Cl CH2OH Et CF3 Cl CH2OM e Et

- 48 043836

Table 5-4

Ria Rib R14 R15 Ria Rib R14 R15 Cl Cl Me H CF3 H Me H Cl Cl Et H CF3 H Et H Cl Cl i-Pr H CF3 H i-Pr H Cl Cl iBu H CF3 H iBu H Cl Cl CH2OH H CF3 H CH2OH H Cl Cl CH2OM e H CF3 H CH2OM e H Cl Cl Me Me CF3 H Me Me Cl Cl Et Me CF3 H Et Me Cl Cl i-Pr Me CF3 H i-Pr Me Cl Cl iBu Me CF3 H iBu Me Cl Cl CH2OH Me CF3 H CH2OH Me Cl Cl CH2OM e Me CF3 H CH2OM e Me Cl Cl Me Et CF3 H Me Et Cl Cl Et Et CF3 H Et Et Cl Cl i-Pr Et CF3 H i-Pr Et Cl Cl iBu Et CF3 H iBu Et Cl Cl CH2OH Et CF3 H CH2OH Et Cl Cl CH2OM e Et CF3 H CH2OM e Et Cl Cl Me i-Pr CF3 H Me i-Pr Cl Cl Et i-Pr CF3 H Et i-Pr Cl Cl i-Pr i-Pr CF3 H i-Pr i-Pr Cl Cl iBu i-Pr CF3 H iBu i-Pr Cl Cl CH2OH i-Pr CF3 H CH2OH i-Pr Cl Cl CH2OM e i-Pr CF3 H CH2OM e i-Pr

- 49 043836

Cl Cl Me CH2CF3 CF3 H Me CH2CF3 Cl Cl Et CH2CF3 CF3 H Et CH2CF3 Cl Cl i-Pr CH2CF3 CF3 H i-Pr CH2CF3 Cl Cl iBu CH2CF3 CF3 H iBu CH2CF3 Cl Cl CH2OH CH2CF3 CF3 H CH2OH CH2CF3 Cl Cl CH2OM e CH2CF3 CF3 H CH2OM e CH2CF3 CF3 Cl Me H CF3 Cl Me i-Pr CF3 Cl Et H CF3 Cl Et i-Pr CF3 Cl i-Pr H CF3 Cl i-Pr i-Pr CF3 Cl iBu H CF3 Cl iBu i-Pr CF3 Cl CH2OH H CF3 Cl CH2OH i-Pr CF3 Cl CH2OM e H CF3 Cl CH2OM e i-Pr CF3 Cl Me Me CF3 Cl Me CH2CF3 CF3 Cl Et Me CF3 Cl Et CH2CF3 CF3 Cl i-Pr Me CF3 Cl i-Pr CH2CF3 CF3 Cl iBu Me CF3 Cl iBu CH2CF3 CF3 Cl CH2OH Me CF3 Cl CH2OH CH2CF3 CF3 Cl CH2OM e Me CF3 Cl CH2OM e CH2CF3 CF3 Cl Me Et CF3 Cl Et Et CF3 Cl i-Pr Et CF3 Cl iBu Et CF3 Cl CH2OH Et CF3 Cl CH2OM e Et

Table 6-1

Ria Rib R16 Ria Rib R16 Cl Cl Me CF3 H Me Cl Cl F CF3 H F Cl Cl NH2 CF3 H NH2 CF3 Cl Me CF3 Cl F CF3 Cl NH2

- 50 043836

Table 6-2

Ria Rib R16 Ria Rib R16 Cl Cl Me CF3 H Me Cl Cl F CF3 H F Cl Cl NH2 CF3 H NH2 CF3 Cl Me CF3 Cl F CF3 Cl NH2

Table 7-1

Ria Rib J Ria Rib J Cl Cl CF3 H Cl Cl \/^CN Me CF3 H \/^CN Me Cl Cl Me Me CF3 H Me Me

- 51 043836

Cl Cl CF3 H x/^^^^^CN Cl Cl Me CF3 H /^CN Me Cl Cl )<X _N CF3 H %Xn Cl Cl CF3 H Cl Cl CF3 H Cl Cl cyclopropyl CF3 H cyclopropyl Cl Cl CF3 H A Cl Cl CF3 H x^^^CN Cl Cl 0 /^ζ^ΝΗΜο CF3 H 0 CF3 Cl CF3 Cl CF3 Cl χ/^-CN Me CF3 Cl CF3 Cl Me Me CF3 Cl cyclopropyl CF3 Cl V^^x^ ^cx / CF3 Cl CF3 Cl Me CF3 Cl x^^^CN CF3 Cl CF3 Cl 0 %^^NHMe

- 52 043836

Table 7-2

R

F

Ria Rib J Ria Rib J Cl Cl X^^CN CF3 H X^Xn Cl Cl X^CN Me CF3 H ^cn Me Cl Cl Me Me CF3 H Me Me Cl Cl CF3 H Cl Cl Me CF3 H Xj^X'N Me Cl Cl /X CF3 H lX Cl Cl * CF3 H CN CN Cl Cl XX CF3 H aX Cl Cl cyclopropyl CF3 H cyclopropyl Cl Cl Ή CF3 H ^XCN Cl Cl X^^CN CF3 H X^^CN ABOUT ABOUT Cl Cl CF3 H CF3 Cl X^^CN CF3 Cl CN CF3 Cl X^cn Me CF3 Cl XX CF3 Cl X^/CN Me Me CF3 Cl cyclopropyl CF3 Cl CF3 Cl ^XCN CF3 Cl S^CN Me CF3 Cl X^/^CN ABOUT CF3 Cl XX CF3 Cl X^^NHMe

- 53 043836

Specific compounds of Formula 1 obtained using the methods and variations thereof described in the preceding Schemes 1-11 and Synthetic Examples 1-5 are presented in the performance tables below. The following abbreviations may be used: conn. stands for compound, t stands for tertiary, c stands for cyclo, Me stands for methyl, Et stands for ethyl and Ph stands for phenyl. Abbreviation Pr. denotes an example followed by a number indicating the number of the example of synthesis in which the compound is prepared.

Melting point (MP) data is presented as a temperature range (eg 122-126). Mass spectral (MS) data is presented in the form of a single numerical value (eg, 542). For mass spectral data (AP+(M+1)), the numerical value given is the molecular weight of the parent molecular ion (M) formed by adding H+ (molecular weight 1) to the molecule to produce the M+1 peak detected by mass spectrometry using chemical ionization at atmospheric pressure (AP+). Alternative molecular ion peaks (eg M+2 or M+4) that occur for compounds containing more than one halogen are not reported.

Indicator table A

Connection No. Ria Rib J Data MP/MS 1 Cl Cl 0 Ur Me H 542 2 CF3 Cl About Ur Me H 575 3 Cl Cl ABOUT Me H 556 4 Cl Cl Oh Ur Me H 570 5 Cl Cl 0 A/ ¹ Me. U Me O 78-82 6 Cl Cl About Azr _Ti Me. JHcr 122-126 7 Cl Cl A.A. Me. U II cr 147-151 43 CF3 H About Ur Me H 106-110

- 54 043836

44 C1 C1 about lLg ^E1 Me Me 584 45 C1 C1 ί / /=o d—b \ d 572 46 C1 C1 O Me Me 570 47 C1 C1 About Me Me H 595 48 C1 C1 ABOUT Me H 581

Indicator table A-1

Indicator table A-2

- 55 043836

Indicator table B

Connection No. Ria Rib J MP/MS data 10 Cl Cl xO N 563 AND CF3 Cl X 597 12 Cl Cl .N. jn 563 13 Cl Cl 563 14 Cl Cl Xi 563 15 Cl Cl xQ/ 562 16 Cl Cl X 563 17 Cl Cl / 563 18 Cl Cl 1> 576

- 56 043836

19 Cl Cl /N Me 577 20 Cl Cl Me 576 21 Cl Cl _z jO Me 577 22 Cl Cl / X=x./ ^N ~~ ^Me f 565 23 Cl Cl [^\ , ./ NH / 551 24 Cl Cl /NH 552 25 Cl Cl Me ' ^N /Vy 566 26 Cl Cl .JO N 553 27 Cl Cl Me. n—N <A> 566 28 Cl Cl 568 29 Cl Cl N7\ /j> H 551 thirty Cl Cl r—-N /X) H 551

- 57 043836

31 Cl Cl ,,13 \Me 565 32 Cl Cl ,, χχ ' ^X ^'CF ₃ 631 49 CF3 H '1 151-155 50 CF3 H wO 153-157 51 CF3 H , o γ/l/ ^N 563 52 Cl Cl O 631 53 Cl Cl ,, xx 593 54 Cl Cl '1 207-208 55 Cl Cl /XX 69-71 56 Cl Cl N. .OMe ,, χχ 183-184 57 Cl Cl Me(X N IQ 202-203

58 Cl Cl <jo Λγ N Me 577 59 Cl Cl Y) /N Me 577 60 Cl Cl ,, X) ΧΧΐΨ Et 590

- 58 043836

Indicator table B-1

Indicator table B-2

- 59 043836

Connection No. Rla J MS data 34 Cl u I N—Et 4/ 584 64 Cl aX N-Me 4 582

Indicator table E

Connection No. Rla Rlb J MP/MS data 35 Cl Cl about CH^^OM 543 36 CF3 Cl about Ch^-^^OM 577 37 CF3 Cl 0 CH^^^OH 563 38 Cl Cl 0 529 39 Cl Cl ABOUT CH^^^OM Me 557 40 Cl Cl ABOUT Ch^^OP Me 543 41 Cl Cl About Ch^'ToM ^Me ^o^ 587 42 Cl Cl ABOUT /Ch^J Me^^J 573 65 CF3 H about CH^^^OM Me 161-165 66 CF3 H O Ch^^^OMs 79-83

- 60 043836

F indicator table

R ¹ ^ || i LP J 1 J rU >00,

Connection No. Ria Rib J MP/MS data 67 CF3 H cyclopropyl 153-157 68 CF3 H Me Me 200-204 69 CF3 H \/^CN Me 524 70 Cl Cl cyclopropyl 511 71 Cl Cl ^ ^CN Me 524 72 Cl Cl O 7^^NH ₂ 256-260 73 Cl Cl 525.1 74 Cl Cl /^|^^CN Me 538.2 75 Cl Cl 0 94-98 76 Cl Cl 0 /^ζ^ΝΗΕί 135-139 77 Cl Cl 536 78 Cl Cl 550

G indicator table

Connection No. Ria Rib J MS data 79 Cl Cl / ^S(O) ₂ Me 604

The compounds of this invention are intended to be used generally as an active ingredient in a composition for controlling an invertebrate pest, then in the form of a preparation comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents that serve as a carrier. The ingredients of the preparation or composition are selected to suit the physical properties of the active ingredient, the method of application and environmental factors such as soil type, humidity and temperature.

The preparations used include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions, oil-in-water emulsions, flowable concentrates and/or suspoemulsions) and other similar forms, which may optionally be concentrated into gels. Common types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion, oil-in-water emulsion, flowable concentrate and suspoemulsion. Common types of non-aqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.

Common types of solid compositions are dusts, powders, granules, pellets, pellets, lozenges, tablets, filled films (including seed coatings) and other types that may be water-dispersible (wettable) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly suitable for seed treatment. The active ingredient can be (micro)encapsulated and then converted into a suspended or solid preparation; Alternatively, the entire active ingredient preparation may be encapsulated (or coated). Encapsulation may allow controlled or delayed release of the active ingredient. An emulsifiable granule combines the advantages of both a preparation in the form of an emulsifiable concentrate and a preparation in the form of a dry granule. Highly concentrated compositions are used mainly as intermediate compositions for the subsequent preparation of the drug.

Nebulized preparations are usually diluted in a suitable medium before nebulization. Such liquid and solid preparations are prepared so that they can be easily diluted in a spray medium, usually water, but in rare cases, another suitable medium such as an aromatic or paraffinic hydrocarbon or vegetable oil. Spray volumes can be from about one to several thousand liters per hectare, but more often from about ten to several hundred liters per hectare. Spray formulations may be formulated as a tank mixture with water or other suitable foliar treatment medium by air application or soil application, or for application to plant growth media. Liquid and dry preparations can be introduced in measured quantities directly into drip irrigation systems and into the furrow when planting plants. Liquid and dry formulations can be applied to crop seeds and other desired vegetation by treating the seeds prior to planting to protect the development of root systems and other in-ground plant parts and/or foliage through systemic uptake.

The formulations typically contain effective amounts of the active ingredient, diluent and surfactant in the following amounts, which add up to 100 percent by weight.

Mass percentage Active ingredient Diluent Superficial active substance Water dispersible and water soluble granules, tablets and powders 0.001-90 0-99.999 0-15 Oil dispersions, suspensions, emulsions, solutions (including emulsifiable concentrates) 1-50 40-99 0-50 Dusts 1-25 70-99 0-5 Granules and pellets 0.001-99 5-99,999 0-15 Highly concentrated compositions 90-99 0-10 0-2

Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (for example, lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al.

- 62 043836

Handbook of Insecticide Dust Diluents, Carriers, 2nd ed., Dorland Books, Caldwell, New Jersey.

Liquid diluents include, for example, water, N,N-dimethylalkanamides (eg N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (eg N-methylpyrrolidinone), alkylphosphates (eg triethylphosphate), ethylene glycol, triethylene glycol, propylene glycol , dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g. light mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerin, glycerol triacetate, sorbitol, aromatic hydrocarbons, dearomatized aliphatic hydrocarbons, alkylbenzenes, alkylnaphthalenes, etones such as cyclohexanone , 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, diacid ester with alkyl and aryl benzoates, γ-butyrolactone, and alcohols which may be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol , n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, cresol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically _C6 - _C22 ), such as seed oils and fruit oils (e.g., olive oil, castor oil, flaxseed oil, sesame oil, corn oil) butter, peanut oil, sunflower oil, grapeseed oil, safflower oil, cottonseed oil, soybean oil, canola oil, coconut oil and palm kernel oil), animal fats (such as beef lard, lard, lard, cod liver oil) fat, fish oil) and mixtures thereof. Liquid diluents also include alkylated fatty acids (eg, methylated, ethylated, butylated), where the fatty acids can be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid solvents are described in Marsden, Solvents Guide, 2nd ed., Interscience, New York, 1950.

The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also called surfactants) typically modify, most often reducing, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, surfactants can be used as wetting agents, dispersants, emulsifiers or defoamers.

Surfactants can be classified as non-ionic, anionic or cationic. Nonionic surfactants useful in the preparation of the present compositions include, but are not limited to, alcohol alkoxylates, such as natural and synthetic alcohol alkoxylates (which may be branched or linear), which are derived from alcohols and ethylene oxide, oxide propylene, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonylphenol ethoxylates and dodecylphenol ethoxylates (derived from phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers derived from ethylene oxide or propylene oxide, and reverse block polymers in which the end blocks are derived from propylene oxide; ethoxylated liquid acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those derived from ethylene oxide, propylene oxide, butene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin derivatives, polyethoxylated esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitan fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd polyethylene glycol resins, graft or graft comb copolymers and star polymers; polyethylene glycols; polyethylene glycol esters of fatty acids; surfactants based on organosilicon compounds; and sugar derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to, alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenylsulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acid or their anhydrides; olefin sulfonates; phosphate esters such as alcohol alkoxylate phosphate esters, alkylphenol alkoxylate phosphate esters and styrylphenol ethoxylate phosphate esters; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; alcohol sulfates; ethoxylated alcohol sulfates; amine and amide sulfonates such as N,N-alkyl taurates; sulfonates of benzene, cumene, toluene, xylene and dodecyl- and tridecylbenzenes; condensed naphthalene sulfonates; naphthalene and alkylnaphthalene sulfonates; sulfonates of fractionated petroleum products; sulfosuccinomates; and sulfosuccinates and derivatives thereof, such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (derived from amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)alkylamine oxides.

In addition, mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants can be used in the present compositions. Nonionic, anionic, and cationic surfactants and their recommended uses are described in a number of publications, including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; A.S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.

The compositions of this invention may also contain excipients and additives that are known to those skilled in the art as substances used in the preparation of formulations (some of which may also function as solid diluents, liquid diluents or surfactants). Such excipients and additives can control pH (buffers), foaming during formulation (antifoams such as polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), growth of microorganisms in the container (antimicrobials), freezing of the product (antifreeze), color (dye/pigment dispersions), leaching (film formers or thickeners), evaporation (evaporation retarders) and other properties of the preparations. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of excipients and additives used in the preparation of preparations include those described in McCutcheon's publications, vol. 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co., PCT Publication WO 03/024222.

The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry vehicle. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of the liquid composition intended for use in the form of an emulsifiable concentrate is immiscible with water, then an emulsifier is usually added to emulsify the active substance-containing solvent upon dilution with water. Active ingredient suspensions with particle diameters up to 2000 µm can be wet milled using grinding media to produce particles with an average diameter of less than 3 µm. Aqueous suspensions can be prepared in the form of ready-made suspension concentrates (see, for example, US 3,060,084) or can be further processed by spray drying to produce water-dispersible granules. Dry formulations typically require the use of dry grinding processes that achieve average particle diameters in the range of 2 to 10 µm. Dusts and powders can be prepared by mixing and usually grinding (for example, using a hammer mill or jet mill). Granules and briquettes can be prepared by spraying the active material onto preformed granular supports or by sintering. See Browning, Agglomeration, Chemical Engineering, December 4, 1967, p. 147-48, Perry's Chemical Engineer's Handbook, 4th ed., McGraw-Hill, New York, 1963, p. 8-57 and following; WO 91/13546. Briquettes can be prepared as described in US 4172714. Water dispersible and water soluble granules can be prepared as described in US 4144050, US 3920442 and DE 3246493. Tablets can be prepared as described in US 5180587, US 5232701 and US 5208030. Films can be prepared as described in GB 2095558 and US 3299566.

More detailed information on the preparation of preparations can be found in the publication T.S. Woods, The Formulator's Toolbox - Product Forms for Modern Agriculture in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks, T.R. Roberts, eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, p. 120-133. See also publications US 3235361, col. 6, line 16 through col. 7, line 19 and examples 10-41; US 3309192, col. 5, line 43 through col. 7, line 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; US 2891855, col. 3, line 66 through col. 5, line 17 and examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, p. 81-96; Hance et al., Weed Control Handbook, 8th ed., Blackwell Scientific Publications, Oxford, 1989; Developments in formulation technology, PJB Publications, Richmond,

- 64 043836

UK, 2000.

In the following examples, all preparations are prepared using traditional methods. Compound numbers indicate compounds in Score Tables A-G. It is believed that one skilled in the art, using the above description, can, without further study, use the present invention to its fullest extent. Therefore, the following examples should be construed as illustrations only and should not be construed as limiting the invention in any way. Percentages are percentages by weight unless otherwise noted.

Example A.

Highly concentrated concentrate Connection 1 98.5% Silica gel 0.5% Synthetic amorphous fine silica 1.0%

Example B.

Wettable powder Connection 3 65.0% Dodecylphenol polyethylene glycol ether 2.0% Sodium lignin sulfonate 4.0% Sodium aluminum silicate 6.0% Montmorillonite (calcined) 23.0%

Example C.

Granule Connection 8 10.0% Attapulgite granules (non-volatile substance, 0.71/0.30 mm; sieves U.S.S. No. 25-50) 90.0%

Example D

Extruded briquette Connection 10 25.0% Anhydrous sodium sulfate 10.0% Unpurified calcium lignin sulfonate 5.0% Sodium alkyl naphthalene sulfonate 1.0% Calcium/magnesium bentonite 59.0%

Example E.

Emulsifiable concentrate Connection 11 10.0% Polyoxyethylene sorbitan hexaoleate 20.0% C6-C10 fatty acid methyl ester 70.0%

Example F

Microemulsion Connection 19 5.0% Polyvinylpyrrolidone-vinyl acetate copolymer 30.0% Alkylpolyglycoside 30.0% Glyceryl monooleate 15.0% Water 20.0%

- 65 043836

Example G.

Seed treatment Connection 20 20.00% Polyvinylpyrrolidone-vinyl acetate copolymer 5.00% Sour montan wax 5.00% Calcium lignin sulfonate 1.00% Polyoxyethylene/polyoxypropylene block copolymers 1.00% Stearyl alcohol (POE 20) 2.00% Polyorganosilane 0.20% Coloring red dye 0.05% Water 65.75%

Example N.

Fertilizer in stick form Connection 33 2.5% Pyrrolidone-styrene copolymer 4.8% Tristyrene ylphenyl 16-ethoxylate 2.3% Talc 0.8% Corn starch 5.0% Slow release fertilizer 36.0% Kaolin 38.0% Water 10.6%

Example I

Suspension concentrate Connection 34 35% Butylpolyoxyethylene/polypropylene block copolymer 4.0% Stearic acid/polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Organosilicon-based defoamer 0.1% 1,2-Benzisothiazolin-3-one 0.1% Water 53.7%

Example J.

Emulsion in water Connection 39 10.0% Butylpolyoxyethylene/polypropylene block copolymer 4.0% Stearic acid/polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Organosilicon-based defoamer 0.1% 1,2-Benzisothiazolin-3-one 0.1% Hydrocarbon based on aromatic petroleum fraction 20.0 Water 58.7%

- 66 043836

Example K.

Oil dispersion Connection 50 25% Polyoxyethylene sorbitan hexaoleate 15% Organically modified bentonite clay 2.5% Fatty acid methyl ester 57.5%

Example L.

Suspoemulsion Compound 61 10.0% Imidacloprid 5.0% Butylpolyoxyethylene/polypropylene block copolymer 4.0% Stearic acid/polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Organosilicon-based defoamer 0.1% 1,2-Benzisothiazolin-3-one 0.1% Hydrocarbon based on aromatic petroleum fraction 20.0% Water 53.7%

Example M.

Suspension concentrate Compound 67 35% Butylpolyoxyethylene/polypropylene block copolymer 4.0% Stearic acid/polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Organosilicon-based defoamer 0.1% 1,2-Benzisothiazolin-3-one 0.1% Water 53.7%

Example N.

Emulsion in water Connection 69 10.0% Butylpolyoxyethylene/polypropylene block copolymer 4.0% Stearic acid/polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Organosilicon-based defoamer 0.1% 1,2-B enz isothiazol in-3-one 0.1% Hydrocarbon based on aromatic petroleum fraction 20.0 Water 58.7%

- 67 043836

Example O.

Oil dispersion Connection 70 25% Polyoxyethylene sorbitan hexaoleate 15% Organically modified bentonite clay 2.5% Fatty acid methyl ester 57.5%

Example R.

Suspoemulsion Connection 71 10.0% Imidacloprid 5.0% Butylpolyoxyethylene/polypropylene block copolymer 4.0% Stearic acid/polyethylene glycol copolymer 1.0% Styrene acrylic polymer 1.0% Xanthan gum 0.1% Propylene glycol 5.0% Organosilicon-based defoamer 0.1% 1,2-Benzisothiazolin-3-one 0.1% Hydrocarbon based on aromatic petroleum fraction 20.0% Water 53.7%

The compounds of this invention are active against a wide range of invertebrate pests. These agricultural pests include invertebrate pests found in a variety of environments, such as, for example, plant foliage, root systems, soil, harvested crops or other food products, or building structures. These agricultural pests include, for example, invertebrate pests that feed on foliage (including leaves, stems, flowers and fruits), seeds, wood or textile fibers and thereby cause damage or damage to, for example, growing or stored crops, forests , greenhouse crops, ornamental plants, nursery-grown plants, stored food or fiber products, or residential or other structures or their contents. It will be apparent to those skilled in the art that not all compounds are equally effective when applied to all developmental stages of all agricultural pests.

Thus, these present compounds and compositions can be used for agronomic purposes to protect field crops from herbivorous invertebrate pests, as well as for non-agricultural purposes to protect other horticultural crops and plants from herbivorous invertebrate pests. This application includes the protection of crops and other plants (i.e., both agricultural and non-agricultural) that contain genetic material that has been genetically engineered (i.e., transgenic) or modified by mutagenesis to impart desirable characteristics. Examples of such characteristics include herbicide tolerance, resistance to herbivorous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant pathogenic fungi, bacteria and viruses), enhanced plant growth, increased tolerance of unfavorable growing conditions such as high or low temperatures, low or high soil moisture and high salinity, increased flowering or fruiting, higher yields, faster ripening, higher quality and/or nutritional value of the harvested product, or improved storage or processing properties of the harvested product. Transgenic plants can be modified to impart many desirable characteristics at once. Examples of plants that have been provided with desirable characteristics by genetic engineering or mutagenesis include corn, cotton, soybean and potato varieties that express the insecticidal toxin Bacillus thuringiensis, such as YIELD GARD®, KNOCKOUT®, STARLINK®, BOLLGARD®, NuCOTN® and NEWLEAF ®, INVICTA RR2 PROTM, and herbicide-tolerant varieties of corn, cotton, soybeans and canola such as ROUNDUP READY®, LIBERTY LINK®, IMI®, STS® and CLEARFIELD®, as well as grain crops expressing N-acetyltransferase (GAT) to provide glyphosate-based herbicide resistance, or crops containing the HRA gene, which provides resistance to acetolactate synthase (ALS)-inhibiting herbicides. The presented compounds and compositions can be characterized by enhanced action, having characteristics given to them by genetic engineering methods or modified by mutagenesis, due to which they enhance

- 68 043836 phenotypic expression or effectiveness of characteristics or increases the effectiveness of the presented compounds and compositions when used to control an invertebrate pest. In particular, the present compounds and compositions may exhibit enhanced effects resulting from the phenotypic expression of proteins or other natural products that are toxic to invertebrate pests, providing greater than additive control effectiveness against these pests.

The compositions of this invention may also optionally include plant nutrients, for example, a fertilizer composition containing at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc and molybdenum. Of particular note are compositions comprising at least one fertilizer composition containing at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium. The compositions of the present invention, which further contain at least one plant nutrient, may be in the form of liquids or solids. Of note are solid preparations in the form of granules, small sticks or tablets. Solid preparations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition in combination with other ingredients included in the preparation, and then preparing the preparation using methods such as granulation or extrusion. Alternatively, solid preparations can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solvent onto a preformed fertilizer composition in the form of size-stable mixtures, such as granules, small sticks or tablets, and then evaporating the solvent.

Non-agricultural applications refer to the control of invertebrate pests in areas other than crop growing fields. Non-agricultural applications of the present compounds and compositions include the control of invertebrate pests of grain in granaries, food and other food products, and textiles such as clothing and carpets. Non-agricultural applications of the present compounds and compositions also include the control of invertebrate pests of ornamental plants, forests, warehouses, roadsides and railroad rights-of-way, and lawns such as lawns, golf courses and rangelands. Non-agricultural uses of the present compounds and compositions also include the control of invertebrate pests in residential areas and other structures that may be occupied by people and/or pets, farm animals, farm animals, zoo animals or other animals. Non-agricultural applications of the present compounds and compositions also include the control of harmful insects, such as termites, which can damage wood or other structural materials used inside buildings.

Examples of agricultural or non-agricultural invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as caterpillars, cutworms, moths, and the subfamilies Heliothines of the family Noctuidae (e.g., Sesamia inferens Walker, corn stalk moth (Sesamia nonagrioides Lefebvre), southern armyworm (Spodoptera eridania Cramer), fall armyworm (Spodoptera frugiperda J.E. Smith), small armyworm (Spodoptera exigua Hubner), cotton armyworm (Spodoptera littoralis Boisduval), striped armyworm (Spodoptera ornithogalli Guenee), upsilon cutworm (Agrotis ipsilon Hufnagel), velvet bean caterpillar (Anticarsia gemmatalis Hubner), green moth (Lithophane antennata Walker), cabbage cutworm (Barathra brassicae Linnaeus), soybean moth (Pseudoplusia includens Walker), cutworm (Trichoplusia ni Hubner), tobacco cutworm (Heliothis virescens Fabricius)); borers, cap moths, web-nest caterpillars, spruce budworms, cabbage butterfly caterpillars and leaf-skeleton pests of the family Pyralidae (e.g. corn borer (Ostrinia nubilalis Hubner), navel orange worm (Amyelois transitella Walker), corn moth (Crambus caliginosellus Clemens), caterpillars of meadow moths (Pyralidae: Crambinae), such as meadow moth (Herpetogramma licarsisalis Walker), sugarcane borer (Chilo infuscatellus Snellen), tomato small borer (Neoleucinodes elegantalis Guenee), green leaf roller (Cnaphalocerus medinalis) , grape budworm (Desmia funeralis Hubner), melon caterpillar (Diaphania nitidalis Stoll), cabbage center larva (Helluala hydralis Guenee), yellow stem borer (Scirpophaga incertulas Walker), early shoot borer (Scirpophaga infuscatellus Snellen), white stem borer (Scirpophaga innotata Walker), shoot borer (Scirpophaga nivella Fabricius), dark-headed rice moth (Chilo polychrysus Meyrick), striped rice moth (Chilo suppressalis Walker), cabbage moth (Crocidolomia binotalis English)); leafrollers, budworms, seed caterpillars and codling moths of the family Tortricidae (e.g. codling moth (Cydia pomonella Linnaeus), grape moth (Endopiza viteana Clemens), eastern peach moth (Grapholita molesta Busck), wild apple citrus moth (Cryptophlebia leucotreta Meyrick), citrus cutworm (Ecdytolopha aurantiana Lima), red-striped budworm (Argyrotaenia velutinana Walker), wavy cutworm (Choristoneura rosaceana Harris), light brown apple

- 69 043836 moth (Epiphyas postvittana Walker), European grape moth (Eupoecilia ambiguella Hubner), bud roller (Pandemis pyrusana Kearfott), omnivorous leaf roller (Platynota stultana Walsingham), currant leaf roller (Pandemis cerasana Hubner), willow leaf roller ( Pandemis heparana Denis & Schiffermuller)) and many other economically important members of the order Lepidoptera (e.g. cabbage moth (Plutella xylostella Linnaeus), pink cotton worm (Pectinophora gossypiella Saunders), gypsy moth (Lymanthria dispar Linnaeus), peach moth (Carposina niponensis Walsingham), codling moth apricot moth (Anarsia lineatella Zeller), potato tuber moth (Phthorimaea operculella Zeller), apple moth (Lithocolletis blancardella Fabricius), Asian apple moth (Lithocolletis ringoniella Matsumura), rice leaf roller (Lerodea eufala Edwards), hawthorn moth ( Leucoptera scitella Zeller)); eggs, larvae and adults of members of the order Blattodea, including cockroaches from the families Blattellidae and Blattidae (for example, the black cockroach (Blatta orientalis Linnaeus), the Asian cockroach (Blatella asahinai Mizukubo), the red cockroach (Blatella germanica Linnaeus), the striped cockroach (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunnea Burmeister), Madeira cockroach (Leucophaea maderae Fabricius), brown cockroach (Periplaneta fuliginosa Service), Australian cockroach (Periplaneta australasiae Fabr.), gray cockroach (Nauphoeta cinerea Olivier) and smooth cockroach (Symploce pallens Stephens)); eggs, leaf-feeding larvae, fruit-feeding larvae, root-feeding larvae, seed-feeding larvae and bladder-feeding larvae, as well as adults of the order Coleoptera, including weevils of the families Anthribidae, Bruchidae and Curculionidae (e.g. cotton weevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrus oryzophilus Kuschel), granary weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oryzae Linnaeus), annual bluegrass weevil (Listronotus maculicollis Dietz), bluegrass weevil (Sphenophorus parvulus Gyllenhal), prowling weevil (Sphenophorus venatus vestitus), Denver weevil (Sphenophorus cicatristriatus Fahraeus)); flea beetles, potato flea beetles, root beetles, leaf beetles, Colorado potato beetles and leaf miners of the family Chrysomelidae (e.g. Colorado potato beetle (Leptinotarsa decemlineata Say), western corn rootworm (Diabrotica virgifera LeConte)); beetles and other beetles from the family Scarabaeidae (for example, Japanese beetle (Popillia japonica Newman), oriental beetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northern beetle (Cyclocephala borealis Arrow), southern beetle (Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and May beetle (Aphodius spp.), black beetle (Ataenius spretulus Haldeman), shiny green beetle (Cotinis nitida Linnaeus), Asian garden beetle (Maladera castanea Arrow), May/June beetle (Phyllophaga spp. ) and common beetle (Rhizotrogus majalis Razoumowsky)); skin beetles from the family Dermestidae; wireworms from the Elateridae family; bark beetles from the family Scolytidae and mealworms from the family Tenebrionidae.

In addition, agricultural and non-agricultural pests include eggs, adults and larvae of members of the order Dermaptera, including earwigs of the family Forficulidae (eg, common earwig (Forficula auricularia Linnaeus), black earwig (Chelisoches morio Fabricius)); eggs, immatures, adults and nymphs of members of the orders Hemiptera and Homoptera, such as horse bugs of the family Miridae, cicadas of the family Cicadidae, leafhoppers (e.g. Empoasca spp.) of the family Cicadellidae, bedbugs (e.g. Cimex lectularius Linnaeus) from the family Cimicidae, lanternflies from the families Fulgoroidae and Delphacidae, humpbacks from the family Membracidae, psyllids from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae, scale insects from the family Pseudococcidae, scale insects from the families Coccidae, Diaspididae and Margarodidae, bedbugs - lace bugs from the family Tingidae, stink bugs from the family Pentatomidae, bugs (for example, the wheat bug (Blissus leucopterus hirtus Montandon) and the southern bug (Blissus insularis Barber)) and other ground bugs from the family Lygaeidae, pennies from the family Cercopidae, squash bugs in the family Coreidae, and red bugs, including cotton red bugs, in the family Pyrrhocoridae.

Agricultural and non-agricultural pests also include eggs, larvae, pupae and adults of members of the order Acari (mites), such as spider mites and red mites of the family Tetranychidae (e.g. red fruit mite (Panonychus ulmi Koch), two-spotted spider mite (Tetranychus urticae Koch ), McDaniel's mite (Tetranychus mcdanieli McGregor), flat mites of the family Tenuipalpidae (for example, citrus flat mite (Brevipalpus lewisi McGregor)), rust mites and bud mites of the family Eriophyidae and other leaf-feeding mites and mites hazardous to human and animal health eg dust mites from the family Epidermoptidae, iron mites from the family Demodicidae, grain mites from the family Glycyphagidae, ticks from the family Ixodidae (e.g. deer tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes holocyclus Neumann), ixodid tick (Dermacentor variabilis Say), the American tick (Amblyomma americanum Linnaeus)) and ticks of the family Argasidae, commonly known as soft ticks (for example, the Argas tick (Ornithodoros turicata), the common Persian tick (Argas radiatus)); horse mites and scabies from the families Psoroptidae, Pyemotidae and Sarcoptidae; eggs,

- 70 043836 adults and immatures of the order Orthoptera, including species of locusts, cicadas and crickets (for example, grasshopper species (for example, Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American locust species (for example, Schistocerca americana Drury), locusts desert locust (Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), bush locust (Zonocerus spp.), house cricket (Acheta domesticus Linnaeus), mole cricket species (e.g. brown mole cricket (Scapteriscus vicinus Scudder) and southern mole cricket (Scapteriscus borellii Giglio -Tos)); eggs, adults and immatures of members of the order Diptera, including leaf miners (e.g. Liriomyza spp., such as tomato leaf miner (Liriomyza sativae Blanchard)), small dipterous insects, fruit flies (Tephritidae), Swedish flies (for example, Oscinella frit Linnaeus), soil-dwelling insect larvae, house flies (for example, Musca domestica Linnaeus), house flies (for example, Fannia canicularis Linnaeus, F. femoralis Stein), autumn flies (for example, Stomoxys calcitrans Linnaeus) , common field flies, small cow flies, carrion flies (for example, Chrysomya spp., Phormia spp.) and other muscoid flying pests, horseflies (for example, Tabanus spp.), gadflies (for example, Gastrophilus spp., Oestrus spp.), larvae of the bovine banded botfly (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), sheep's fly (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp. ), midges (for example, Prosimulium spp., Simulium spp.), biting midges, mosquitoes, sciarids and other Nematocera; eggs, adults and immatures of the order Thysanoptera, including tobacco thrips (Thrips tabaci Lindeman) and other leaf-feeding thrips; insect pests from the order Hymenoptera, including ants from the family Formicidae, including the Florida carpenter ant (Camponotus floridanus Buckley), the red carpenter ant (Camponotus ferrugineus Fabricius), the Pennsylvania carpenter ant (Camponotus pennsylvanicus De Geer), the white-legged ant (Technomyrmex albipes fr. Smith), big-headed ants (Pheidole sp.), ghost ant (Tapinoma melanocephalum Fabricius); ant turf ant (Tetpamorium caespitum Linnaeus), corn ant (Lasius alienus Forster) and odorous house ant (Tapinoma sessile Say). Other members of the order Hymenoptera include bees (including carpenter bees), hornets, wasps, burrowing wasps, and sawflies (Neodiprion spp.; Cephus spp.); insect pests of the order Isoptera include termites from the families Termitidae (e.g., Macrotermes sp., Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen), oriental Subterranean termite (Reticulitermes flavipes Kollar), Western subterranean termite (Reticulitermes hesperus Banks), Taiwanese subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (Incisitermes immigrans Snyder), drywood termite (Cryptotermes brevis Walker), drywood termite oven drunken termite (Incisitermes snyderi Light), southern subterranean termite (Reticulitermes virginicus Banks), western drywood termite (Incisitermes minor Hagen), wood termites such as Nasutitermes sp., and other economically important termites; insect pests of the order Thysanura include silverfish (Lepisma saccharina Linnaeus) and Thermobia domestica Packard; Insect pests of the order Mallophaga include the head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus Linnaeus), chicken louse (Menacanthus stramineus Nitszch), dog louse (Trichodectes canis De Geer), chicken louse (Goniocotes gallinae De Geer) ), sheep louse (Bovicola ovis Schrank), bovine louse (Haematopinus eurysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and gnawing parasitic lice that attack people and animals; insect pests of the order Siphonoptera include the rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), chicken flea (Ceratophyllus gallinae Schrank), poultry flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas that infect mammals and birds. Other arthropod pests covered include spiders in the order Araenae, such as the brown recluse spider (LoKcosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and millipedes in the order Scutigeromorpha, such as the common flycatcher (Scutigera coleoptrata Linnaeus).

Examples of invertebrate pests of grain stored in granaries: large grain borer (Prostephanus truncatus), small grain borer (Rhyzopertha dominica), rice weevil (Stiophilus oryzae), corn weevil (Stiophilus zeamais), Chinese weevil (Callosobruchus maculatus), chestnut beetle (Tribolium) castaneum), granary weevil (Stiophilus granarius), Indian meal moth (Plodia interpunctella), mealworm (Ephestia kuhniella) and small or red mealworm (Cryptolestis ferrugineus).

The compounds of this invention are active against pests from the order Lepidoptera (for example, Alabama argillacea Hubner, Archips argyrospila Walker, A. rosana Linnaeus and other species of Archips, Chilo suppressalis Walker rice stem), Cnaphalocrosis medinalis Guenee (rice leaf roller),

- 71 043836

Crambus caliginosellus Clemens (corn root moth), Crambus teterrellus Zincken (grass moth), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny worm), Earias vittella Fabricius (spotted armyworm), Helicoverpa armigera Hubner (bollworm), Helicoverpa Zea Boddie (cotton scoops), Heliothis virescens fabricius (tobacco leaflets), Herpetogramma Licarsalis Walker, Lobesia Botrana Denis & Schiffermuller (grape Listenge), Pektinoph Ora Gossypiella Saunders (pink boxed worm), PhylCnistis Citrella Stinton (mining citrus molor) , Pieris brassicae Linnaeus (cabbage white moth), Pieris rapae Linnaeus (turnip white moth), Plutella xylostella Linnaeus (cabbage moth), Spodoptera exigua Hubner (small armyworm), Spodoptera litura Fabricius (Asian cotton bollworm, bunch budworm), Spodoptera frugiperda J.E. Smith (grass cutworm), Trichoplusia ni Hubner (ni Hubner) and Tuta absoluta Meyrick (tomato moth).

The compounds of this invention are active against pests from the order Homoptera, including Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (alfalfa aphid), Aphis fabae Scopoli (bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (meadowsweet aphid), Aulacorthum solani Kaltenbach (potato aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rose apple aphid ), Eriosoma lanigerum Hausmann (apple blood aphid), Hyalopterus pruni Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (mustard leaf aphid), Metopolophium dirrhodum Walker (cereal aphid), Macrosiphum euphorbiae Thomas (potato leaf aphid), Myzus persicae Sulzer ( peach aphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry aphid), Schizaphis graminum Rondani (cereal aphid), Sitobion avenae Fabricius (great cereal aphid), Therioaphis maculata Buckton (clover aphid), Toxoptera aurantii Boyer de Fonscolombe (citrus aphid) and Tokcoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (hermes); Phylloxera devastatrix Pergande (phylloxera hickory); Bemisia tabaci Gennadius, Bemisia argentifolii Bellows and Perring, Dialeurodes citri Ashmead and Trialeurodes vaporariorum Westwood; Empoasca fabae Harris (potato planthopper), Laodelphax striatellus Fallen (small brown planthopper), Macrolestes quadrilineatus Forbes (aster planthopper), Nephotettix cinticeps Uhler (green planthopper), Nephotettix nigropictus Stal (rice planthopper), Nilaparvata lugens Stal (brown planthopper), Peregrinus maidis Ashmead (corn leafhopper), Sogatella furcifera Horvath (white-backed leafhopper), Sogatodes orizicola Muir (rice delphacid), Typhlocyba pomaria McAtee (white apple leafhopper), Erythroneoura spp. (grape leafhoppers); Magicidada septendecim Linnaeus (periodic cicada); Icerya purchasi Maskell (Australian scale insect), Quadraspidiotus perniciosus Comstock (California scale insect); Planococcus citri Risso (citrus bug); Pseudococcus spp. (complex of other mealybugs); Cacopsylla pyricola Foerster (pear psyllid), Trioza diospyri Ashmead (persimmon psyllid).

The compounds of the present invention are active against members of the order Hemiptera, including Acrosternum hilare Say, Anasa tristis De Geer, Blissus leucopterus Say, Cimex lectularius Linnaeus, Corythuca gossypii Fabricius (cotton bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus

Herrich-Schaffer (cotton bug), Euchistus servus Say (brown planthopper), Euchistus variolarius Palisot de Beauvois (single-spotted stink bug), Graptosthetus spp. (complex terrestrials), Leptoglossus corculus Say (pine seed bug), Lygus lineolaris Palisot de Beauvois (field bug), Nezara viridula Linnaeus (green vegetable bug), Oebalus pugnax Fabricius (rice bug), Oncopeltus fasciatus Dallas (bug -soldier), Pseudatomoscelis seriatus Reuter (cotton grass bug). Other insect orders controlled by solid forms of Compound 1 include Thysanoptera (e.g., Frankliniella occidentalis Pergande), Scirthothrips citri Moulton, Sericothrips variabilis Beach, and Thrips tabaci Lindeman. onion); as well as the order Coleoptera (for example, Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican legume) and wireworms from the genera Agriotes, Athous or Limonius).

Of note is the use of the compounds of this invention for the control of cabbage moth (Plutella xylostella). Of note is the use of the compounds of this invention for the control of armyworm (Spodoptera frugiperda). Of note is the use of the compounds of this invention for the control of Western flower thrips (Frankliniella occidentalis). Of note is the use of the compounds of this invention for the control of potato leafhopper (Empoasca fabae). Of note is the use of the compounds of this invention for the control of corn delphacid (Peregrinus maidis). Of note is the use of the compounds of this invention for the control of melon aphids (Aphis gossypii). Of note is the use of the compounds of this invention for the control of green peach aphids (Myzus persicae). Of note is the use of the compounds of this invention

- 72 043836 for the control of tobacco whitefly (Bemisia tabaci).

The compounds of the present invention can also be used to increase the vigor of a crop. This method involves contacting a crop (e.g., foliage, flowers, fruits, or roots) or seeds from which the crop is grown with a compound of Formula 1 in an amount sufficient to achieve the desired vigor-increasing effect (i.e., in a biologically effective amount ). Typically, the compound of formula 1 is used in the form of a formulated composition. Although the compound of formula 1 is often applied directly to the crop or its seeds, it may nevertheless be applied to the location of the crop, i.e. to the site of the crop habitat, in particular, to the portion of the habitat that is in close proximity, which allows the compound of formula 1 to migrate to the crop. A location suitable for this application method most often includes a growing medium (ie, a medium that provides nutrients to the plant), usually the soil in which the plant is grown. Accordingly, treating a crop to increase the vigor of the crop involves contacting the crop, the seed from which the crop is grown, or the location of the crop with a biologically effective amount of a compound of formula 1.

Increases in crop vigor may result in one or more of the following detectable effects:

(a) optimal survival rate of the crop, characterized by excellent seed germination, emergence of seedlings and resistance of the crop to lodging;

(b) enhanced crop growth, characterized by rapid and complete growth of foliage (eg, as measured by leaf area index), plant height, number of shoots (eg for rice), root mass and total dry matter mass of the crop's vegetative mass;

(c) yield improvement, characterized by time to flower, duration of flowering, number of flowers, total biomass accumulation (i.e. yield) and/or degree of marketability of the fruit or grain produced (i.e. quality of the product produced);

(d) increased ability of the crop to resist or prevent infectious plant diseases and infestations by arthropods, nematodes or soft-bodied pests; and (e) increased ability of the crop to withstand adverse environmental stresses, such as exposure to extreme temperatures, unfavorable humidity, or phytotoxic chemicals.

The compounds of the present invention can increase the vigor of treated plants compared to untreated plants by killing or preventing the feeding of herbivorous invertebrate pests in the plant's habitat. In the absence of such control of herbivorous invertebrate pests, pests reduce plant vigor through their consumption of plant tissue or plant sap, or the spread of plant pathogens such as viruses. Even in the absence of herbivorous invertebrate pests, the compounds of the invention can increase plant vigor as a result of modifying plant metabolism. Generally, crop vigor will be most significantly increased by treating the plant with a compound of the invention if the plant is grown in a non-ideal environment, i.e. in an environment that includes one or more aspects that are unfavorable to the plants achieving the full genetic potential that would be achieved in an ideal environment.

Of note is a method for increasing the vigor of a crop where the crop is grown in an environment that includes herbivorous invertebrate pests. In addition, of note is a method of increasing the vigor of a crop wherein the crop is grown in an environment free of herbivorous invertebrate pests. Also of note is a method of increasing the vigor of a crop wherein the crop is grown in a medium containing an amount of moisture less than the ideal amount to support growth of the crop. Noteworthy is a method for increasing the vigor of a crop, wherein the crop is rice. Also noteworthy is a method for increasing the vigor of a crop, wherein the crop is corn. Also noteworthy is a method for increasing the vigor of a crop, wherein the crop is soybean.

The compounds of this invention may also be mixed with one or more other biologically active compounds or agents, including insecticides, fungicides, nematicides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as molt inhibitors and root stimulants, chemosterilants, chemical signaling devices

- 73 043836 substances, repellents, attractants, pheromones, eating stimulants, other biologically active compounds or entomopathogenic bacteria, viruses or fungi, for the formation of a multicomponent pesticide having an even wider range of agrotechnical and non-agrotechnical applications. Thus, the present invention also relates to a composition comprising a biologically effective amount of a compound of formula 1, at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents and at least one additional biologically active compound or facilities. In connection with the mixtures of the present invention, other biologically active compounds or agents may be formulated together with the present compounds comprising the compounds of Formula 1 to form a premix, or other biologically active compounds or agents may be prepared separately from the present compounds comprising the compounds of Formula 1, and the two formulations are combined together prior to use (eg, in a nebulizer) or, alternatively, administered sequentially.

Examples of such biologically active compounds or agents with which the compounds of this invention can be formulated are insecticides such as abamectin, acephate, acequinocyl, acetamiprid, acrinatrine, afidopyropene ([(3S,4R,4aR,6S,6aS,12R, 12aS,12bS)-3[(cyclopropylcarbonyl)-oxy]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl11- oxo-9-(3-pyridinyl)-2NDSH-naphtho[2D-b]-pyrano[3,4-e]pyran-4-yl]methylcyclopropanecarboxylate), amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, benfuracarb, bensultap, bifenthrin, bifenazate, bistrifluron, borate, buprofezin, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentesine, clothianidin, cyantraniliprole (3-bromo-1-(3 -chloro-2-pyridinyl)-K-[4-cyano-2-methyl-6[(methylamino)carbonyl]phenyl]-1 H-pyrazole-5-carboxamide), cyclaniliprole (3-bromo-K-[2- bromo-4-chloro6-[[(1-cyclopropylethyl)-amino]carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide), cycloprothrin, cycloxapride ((5S,8R )-1-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro-5,8epoxy-1H-imidazo[1,2-a]azepine ), cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gammacyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dipfenthiuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate , dinotefuran, diophenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenitrothion, phenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flometoquine (2-ethyl-3,7-dimethyl-6-[4-(trifluoromethoxy)phenoxy]- 4-quinolinyl methyl carbonate), flonicamide, flubendiamide, flucitrinate, flufenerim, flufenoxuron, flufenoxystrobin (methyl (aE)-2-[[2-chloro4-(trifluoromethyl)phenoxy]methyl]-a-(methoxymethylene)benzene acetate), flufensulfone (5-chloro-2-[(3,4,4trifluoro-3-buten-1-yl)sulfonyl]-thiazole), fluhexaphone, fluopyram, flupiprole (1-[2,6-dichloro-4(trifluoromethyl)phenyl] -5-[(2-methyl-2-propen-1 -yl)amino]-4-[(tri-fluoromethyl)sulfinyl]-1 H-pyrazole-3 carbonitrile), flupyradifurone (4-[[(6-chloro -3-pyridinyl)methyl](2,2-difluoroethyl)amino]-2(5H)furanone), fluvalinate, tau-fluvalinate, fonofos, formetanate, fosthiazate, halofenoside, heptafluthrin ([2,3,5,6-tetrafluoro -4-(methoxymethyl)phenyl]methyl 2,2-dimethyl-3-[(1Z)-3,3,3-trifluoro-1-propey-1yl]cyclopropanecarboxylate), hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, meperfluthrin ([2,3,5,6-tetrafluoro-4(methoxymethyl)phenyl]methyl (1R,3S)-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate) , metaflumizone, metaldehyde, methamidophos, methidathione, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, methoxyfenozide, metofluthrin, monocrotophos, monofluorthrin ([2,3,5,6-tetrafluoro-4(methoxymethyl)-phenyl]methyl 3-(2 -cyano-1-propen-1-yl)-2,2-dimethylcyclopropane-carboxylate), nicotine, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, fosalone, phosmet, phosphamidon, pirimicarb , profenofos, profluthrin, propargite, protrifenbut, piflubumid (1,3,5-trimethyl-K-(2-methyl-1-oxopropyl)-K-[3-(2-methylpropyl)-4-[2,2,2 -trifluoro-1methoxy-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole-4-carboxamide), pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazone, pyriminostrobin (methyl (aE)-2-[[[2- [(2,4dichlorophenyl)amino]-6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-a-(methoxymethylene)-benzene acetate), pyriprole, pyriproxyfen, rotenone, ryanodine, silafluofen, spinetoram, spinosad, spirodiclofen, spiromesifen , spirotetramate, sulprofos, sulfoxaflor (H-[methyloxido[1-[6-(trifluoromethyl)-3pyridinyl]ethyl]-λ ⁴ -sulfanilidene]cyanamide), tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, tetramethylfluthrin ( [2,3,5,6-tetra-fluoro-4-(methoxymethyl)phenyl]methyl 2,2,3,3-tetramethylcyclopropane-carboxylate), tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, thioxazafen (3- phenyl-5-(2-thienyl)-1,2,4-oxa-diazole), tolfenpyrad, tralomethrine, triazamate, trichlorfon, triflumesopyrim (2,4-dioxo-1-(5-pyrimidinylmethyl)-3-[3( trifluoromethyl)phenyl]-2H-pyrido[1,2-a]pyrimidinium internal salt), triflumuron, deltaendotoxins of Bacillus thuringiensis bacteria, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.

Insecticides of note include abamectin, acetamiprid, acrinatrine, afidopyropene,

- 74 043836 amitraz, avermectin, azadirachtin, benfuracarb, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cycloprothrin, cyfluthrin, beta-cyfluthrin, cygal Otrin, gamma-cyhalothrin, lambda -cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diophenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenitrothion, phenothiocarb, fenoxycarb, fenvalerate, fipronil, flometoquine, fl onykamide, flubendiamide , flufenoxuron, flufenoxystrobin, flufensulfone, flupiprole, flupyradifuron, fluvalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, meperfluthrin, metaflumizone, methiodicarb, methomyl, methoprene, methoxy fenozide, metofluthrin, monofluorthrin, nitenpyram, nithiazine, novaluron , oxamyl, pyflubumide, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriminostrobin, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramate, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thios ultrasodium, tralomethrine, triazamate , triflumesopyrim, triflumuron, delta-endotoxins of Bacillus thuringiensis bacteria, all strains of Bacillus thuringiensis bacteria and all strains of nuclear polyhedrosis viruses.

One embodiment of biological agents for mixing with the compounds of this invention includes entomopathogenic bacteria, such as Bacillus thuringiensis, and encapsulated delta endotoxins of Bacillus thuringiensis bacteria, such as the bioinsecticides MVP® and MVPII®, prepared using the CellCap® process (CellCap®, MVP ® and MVPII® are trademarks of Mycogen Corporation, Indianapolis, Indiana, USA); entomopathogenic fungi such as muscardine fungi; and entomopathogenic (both natural and genetically modified) viruses, including baculovirus, nuclear polyhedrosis virus (NPV), such as Helicoverpa zea bollworm virus (HzNPV), Anagrapha falcifera bollworm virus (AfNPV); and granulosa virus (GV), such as Cydia pomonella codling moth granulosa virus (CpGV).

Of particular note is a combination in which the invertebrate pest control active ingredients belong to a different class of chemical compounds or site of action than the compound of formula 1. In particular cases, the combination with at least one other invertebrate pest control active ingredient , which has a similar spectrum of action, but a different site of action, will be especially effective for combating invertebrate pests resistant to plant protection products. Therefore, the composition of the present invention may further include a biologically effective amount of at least one additional invertebrate pest control active ingredient having a similar spectrum of action, but belonging to a different chemical class or having a different site of action. These additional biologically active compounds or agents include, but are not limited to, acetylcholinesterase (AChE) inhibitors such as methomyl, oxamyl, thiodicarb, triazamate, and chlorpyrifos organophosphates; gamma-aminobutyric acid (GABA)-dependent chloride channel antagonists such as the cyclodienes dieldrin and endosulfan, and the phenylpyrazoles ethiprole and fipronil; sodium channel modulators such as the pyrethroids bifenthrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambdacyhalothrin, cypermethrin, deltamethrin, dimefluthrin, esfenvalerate, metofluthrin and profluthrin; nicotinic acetylcholine receptor (nAChR) agonists such as the neonicontinoids acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam, and sulfoxaflor; allosteric nicotinic acetylcholine receptor (nAChR) activators such as the spinosyns spinetoram and spinosad; chloride channel activators such as the avermectins abamectin and emamectin; uvenile hormone mimics such as diophenolan, methoprene, fenoxycarb and pyriproxyfen; selective food blockers of homoptera insects, such as pymetrozine and flonicamid; mite growth inhibitors such as etoxazole; mitochondrial ATP synthase inhibitors such as propargite; uncouplers for oxidative phosphorylation by disrupting the proton gradient, such as chlorfenapyr; nicotinic acetylcholine receptor (nAChR) channel blockers such as the nereistoxin analogues Cartap; chitin biosynthesis inhibitors such as the benzoylureas flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron, and buprofezin; agents that disrupt the molting of dipteran insects, such as cyromazine; ecdysone receptor agonists such as the diacylhydrazines methoxyfenozide and tebufenozide; octopamine receptor agonists such as amitraz; inhibitors of mitochondrial electron transport complex III such as hydramethylnon; mitochondrial electron transport complex I inhibitors such as pyridabene; voltage-gated sodium channel blockers such as indoxacarb; acetyl-CoA carboxylase inhibitors such as tetronic and tetramic acids spirodiclofen, spiromesifen and spirotetramate; inhibitors of mitochondrial electron transport complex II, such as the β-ketonitriles cyenopyrafen and cyflumetofen; ryanodine receptor modulators such as the anthranil diamides chlorantraniliprole, cyantraniliprole and cyantraniliprole, diamides such as flubendiamide, and ryanodine receptor ligands such as ryanodine; compounds for which the target site is

- 75 043836 responsible for biological activity, unknown or not described, such as azadirachtin, biphenazate, pyridalyl, pyrifluquinazone and triflumesopyrim; microbial midgut membrane disruptors of insects, such as the bacteria Bacillus thuringensis, and the endotoxins they produce, and the bacteria Bacillus sphaericus; and biological agents, including nuclear polyhedrosis viruses (NPV) and other naturally occurring or genetically modified viruses.

Additional examples of biologically active compounds or agents with which the compounds of this invention may be formulated include fungicides such as acibenzolar-S-methyl, aldimorph, amethoctradine, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M ), benodanil, benomyl, benthiavalicarb (including benthiavalicarbisopropyl), benzovindiflupyr, betoxazine, binapacryl, biphenyl, bitertanol, bixaphen, blasticidinS, boscalid, bromuconazole, bupirimate, butiobate, carboxin, carpropamide, captafol, captan, carbendazim, chlorneb, chlorothalonil , chlozolinate, copper hydroxide, copper oxychloride, copper sulfate, coumoxystrobin, cyazofamide, cyflufenamide, cymoxanil, cyprocognazole, cyprodinil, dichlofluanid, diclocimet, diclomesin, dicloran, dietofencarb, difenoconazole, diflumetorim, dimethyrimol, dimethomorph, dimoxystrobin, diniconazole (including diniconazole- M), dinocap, dithianone, dithiolans, dodemorph, dodin, econazole, etaconazole, edifenphos, enoxastrobin (also known as enestroburin), eroxiconazole, etaboxam, ethirimol, etridiazole, famoxadone, fenamidone, phenaminstrobin, fenarimol, fenbuconazole, fenfuram, fenhexamide, fenoxanil , fenpiclonil, fenpropidine, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, flometoquine, fluazinam, fludioxonil, flufenoxystrobin, flumorph, fluopicolide, fluopyram, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flut ianil, flutolanil, flutriafol, fluxapyroxad, folpet , phthalide (also known as phthalide), fuberidazole, furalaxyl, furamethpyr, hexaconazole, hymexazole, guazatin, imazalil, imibenconazole, iminoctadine albesilate, iminoctadine triacetate, iodicarsb, ipconazole, isofetamide, iprobenphos, iprodione, iprovalicarb, isoprothiolane, isopyr deputy, isothianil, kasugamycin , kresoxim-methyl, mancozeb, mandipropamide, mandestrobin, maneb, mapanipirin, mepronil, meptildinocap, metalaxyl (including metalaxyl-M/mefenoxam), metconazole, metasulfocarb, metiram, metominostrobin, metrafenone, myclobutanil, naphthitine, neo-azocine (methanarsone you ferric iron), nuarimol, octilinone, ofurac, orysastrobin, oxadixil, oxathiapiproline, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencisuron, penflufen, penthiopyrad, perfurazoate, phosphorous acid (including its salts, for example, fosetyl aluminum) , picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, proquinazide, prothiocarb, prothioconazole, pyraclostrobin, pyramethastrobin, pyraoxystrobin, pyrazofos, piribencarb, pyributacarb, pyrifenox, pyriophenone, perisoxazole, pyrimethanil , pyrifenox, pyrrolnitrin, pyroquilon , quinconazole, quinmethionate, quinoxifene, quintozene, silthiofame, sedaxane, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquine, tekloftalam, tekloftalam, teknazene, terbinafine, tetraconazole, thiabendazole, trifluzamide, thiophanate, tekl ophthalam-methyl, thiram, tiadinil, tolclofosmethyl , tolprocarb, tolifluanide, triadimefon, triadimenol, triarimol, triazoxide, tribasic copper sulfate, triclopyricarb, tridemorph, trifloxystrobin, triflumizole, trimorphamide tricyclazole, trifloxystrobin, triforin, triticonazole, uniconazole, validamycin, valifenalate (also known as valifenal), vinclozolin , zineb, ziram, zoxamide and 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl -3-(trifluoromethyl)-1 H-pyrazol-1 -yl]ethanone; nematicides such as fluopyram, spirotetramate, thiodicarb, fosthiazate, abamectin, iprodione, fluensulfone, dimethyl disulfide, thioxazafen, 1,3-dichloropropene (1,3-D), metam (sodium and potassium), dazomet, chloropicrin, fenamiphos, ethoprofos, cadusafos, terbufos, imitsiafos, oxamyl, carbofuran, thioxazafen, Bacillus firmus and Pasteuria nishizawae; bactericides such as streptomycin; acaricides such as amitraz, quinomethionate, chlorobenzilate, cyhexatine, dicofol, dienochlor, etoxazole, phenazachine, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad.

In particular cases, combinations of a compound of this invention with other biologically active (particularly in relation to invertebrate pest control) compounds or agents (ie active ingredients) result in enhanced effects. It is always desirable to reduce the amount of active ingredients released into the environment while still providing effective pest control. When more effective invertebrate pest control is carried out at application rates that produce satisfactory agronomic results for invertebrate pest control levels, such combinations may be advantageous in terms of reducing crop production costs and reducing environmental stress.

The compounds of this invention and compositions thereof can be applied to plants that have been genetically transformed to express proteins that are toxic to invertebrate pests (such as the delta endotoxins of the bacterium Bacillus thuringiensis). Such application may provide a broader spectrum of plant protection and may be desirable for the control of plant protection resistance in invertebrate pests. Exogenously applied compounds of this invention in combination with toxin-expressing proteins can provide enhanced control of invertebrate pests.

Detailed information on these crop protection products (i.e. insecticides, fungicides, nematicides, acaricides, herbicides and biologicals) is provided in The Pesticide Manual, 13th edition, C.D.S. Tomlin, ed., British Crop Protection Council, Farnham, Surrey, UK, 2003; and The BioPesticide Manual, 2nd edition, L.G. Copping, ed., British Crop Protection Council, Farnham, Surrey, UK, 2001.

Invertebrate pest control is carried out for agricultural and non-agricultural purposes by applying one or more compounds of this invention, usually in the form of a composition in a biologically effective amount, to the pest habitat, including the agricultural and/or non-agricultural location of the infestation, to the area being protected, or directly on agricultural pests against which control is carried out.

Thus, the present invention includes a method of controlling an invertebrate pest for agronomic and/or non-agricultural purposes, comprising contacting the invertebrate pest or its habitat with a biologically effective amount of one or more of the compounds of the invention or a composition comprising at least one such compound, or with a composition comprising at least one such compound and a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the invention and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions, wherein the additional active compound is present in the same granule as the compound of the invention, or in granules that are separate from granules of the compound according to the invention.

To achieve contact with a compound or composition of the invention to protect a field crop from invertebrate pests, the compound or composition is typically applied to crop seeds prior to planting, to foliage (e.g., leaves, stems, flowers, fruits) of crops, or to soil or another growing medium before or after planting the crop.

One embodiment of the contact method is spraying. Alternatively, a granular composition comprising a compound of the invention may be applied to foliage or soil. The compounds of this invention may also be effectively delivered through plant uptake resulting from contacting the plant with a composition comprising a compound of this invention, applied by soaking the soil with a liquid formulation, applying a granular formulation to the soil, treating boxes of planting material in nurseries, or dipping planting material. material. It should be noted that the composition of the present invention is in the form of a liquid preparation for soil impregnation. Additionally, a method of controlling an invertebrate pest comprises contacting the invertebrate pest or its habitat with a biologically effective amount of a compound of the present invention or a composition comprising a biologically effective amount of a compound of the present invention. In addition, it should be noted that the method where the habitat is the soil, and the composition is applied to the soil in the form of a liquid preparation for impregnation of the soil. In addition, it should be noted that the compounds of this invention are also effective when applied topically to the site of infection. Other methods of contact include application of the compound or composition of the invention by direct and after-release sprays, aerial sprays, gels, seed pelleting, microencapsulation, systemic aspiration, baits, tags, boluses, foggers, fumigants , aerosols, dusts and many other options. One embodiment of the contact method is a size-stable fertilizer granule, stick or tablet comprising a compound or composition of the invention. The compounds of this invention can also be used for impregnation of materials from which devices for controlling invertebrate pests (eg, mosquito nets) are made.

The compounds of the invention are used in the treatment of plants as a whole, plant parts and seeds. Plant and seed varieties and plant cultivars can be obtained by traditional methods of propagation and crossing, or by genetic engineering methods. Genetically modified plants and seeds (transgenic plants and seeds) are plants and seeds in which a heterologous gene (transgene) has been stably integrated into the genome of the plant or seed. A transgene, which is identified by its specific location in the plant genome, is called a transformation entity or transgenic entity.

Cultivars of genetically modified plants and seeds that can be treated in accordance with the invention include varieties that are resistant to one or more biotic stresses (agricultural pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, cold temperature, soil salinity, etc.) or which have other required characteristics. Plants and seeds can be genetically modified to provide beneficial characteristics, such as herbicide resistance, pest resistance, modified oil content, or drought tolerance.

Treatment of genetically modified plants and seeds with the compounds of the invention may result in superadditive or enhanced effects. For example, reduced application rates, broadened spectrum of activity, increased resistance to biotic/abiotic stresses, or improved shelf life may be greater than would be expected from the simple additive effects of applying compounds of the invention to genetically modified plants and seeds. .

The compounds of this invention can also be used in seed treatments to protect seeds from invertebrate pests. For purposes of the present invention and claims, seed treatment involves contacting the seeds with a biologically effective amount of a compound of the invention, which is typically formulated in the form of a composition of the invention. This seed treatment protects the seeds from soil-dwelling invertebrate pests, and typically the seed treatment may also protect the root system and other plant parts in contact with the soil in which seedlings develop from germinating seeds. The seed treatment may also provide foliar protection as a result of movement of the compound of this invention or the second active ingredient within the developing plant. Seed treatments can be applied to all types of seeds, including seeds that will germinate plants that have been genetically transformed to exhibit specialized, desired properties. Typical examples include examples of the expression of proteins that are toxic to invertebrate pests, such as the bacterial toxin Bacillus thuringiensis, or examples of the expression of an enzyme that provides herbicide resistance, such as glyphosate acetyltransferase, which provides resistance to the herbicide glyphosate. Treatment of seeds with the compounds of this invention can also increase the vigor of plant growth from seeds.

One method of treating seeds is to spray or dust the seeds with a compound of the invention (ie in the form of a formulated composition) before sowing the seeds. Compositions prepared for treating seeds typically include a film-forming agent or adhesive. Therefore, generally, the seed coating composition of the present invention includes a biologically effective amount of a compound of Formula 1 and a film-forming agent or adhesive. The seed coating can be applied by spraying a liquid-flowing suspension concentrate directly onto the seed bed as it is tumbled and then drying the seed. Alternatively, other types of preparations such as wettable powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be applied to the seeds by spraying. This process is used, in particular, for applying film coatings to seeds. Various coating processes and equipment are well known to those skilled in the art. Suitable processes include those described in P. Kosters et al., Seed treatment: Progress and Prospects, 1994, BCPC Monograph No. 57, and the literature cited therein.

The compounds of formula 1 and their compositions, either alone or in combination with other insecticides, nematicides and fungicides, are used, in particular, in the treatment of seeds of agricultural crops, including, but not limited to, maize or corn, soybeans, cotton, cereals (for example , wheat, oats, barley, rye and rice), potatoes, vegetables and oilseed rape.

Other insecticides with which the compounds of formula 1 can be formulated to form mixtures for use in seed treatments include abamectin, acetamiprid, acrinatrine, amitraz, avermectin, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alphacypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diophenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, phenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, flufenoxuron, fluvalinate, formetanate, fosthiazate, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, metaflumizone, methiocarb, methomyl, methoprene, meth oxyfenozide, nitenpyram, nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramate, sulfoxaflor, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap sodium, tralomethrine, triazamate, triflumuron , delta-endotoxins bacteria Bacillus thuringiensis, all strains of Bacillus thuringiensis bacteria and all strains of nuclear polyhedrosis viruses.

Fungicides with which compounds of formula 1 can be formulated to form mixtures used in seed treatments include amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethomorph, fluazinam, fludioxonil, fluquinconazole, fluopicolide, fluoxastrobin, flutriafol , fluxapyroxad, ipconazole, iprodione, me- 78 043836 thalaxyl, mefenoxam, metconazole, myclobutanil, paclobutrazol, penflufen, picoxystrobin, prothioconazole, pyraclostrobin, sedaxane, silthiophame, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trif loxystrobin and triticonazole.

Compositions comprising compounds of Formula 1 used for seed treatment may further include bacteria and fungi that have the ability to provide protection against the harmful effects of plant pathogenic fungi or bacteria and/or soil-borne animals such as nematodes. Bacteria that have nematicidal capabilities may include, but are not limited to, Bacillus firmus, Bacillus cereus, Bacillius subtiliis and Pasteuria penetrans. A suitable strain of Bacillus firmus is strain CNCM 1-1582 (GB-126), which is sold under the brand name BioNemTM. A suitable strain of Bacillus cereus is strain NCMM I-1592. Both Bacillus strains are disclosed in US Pat. No. 6,406,690. Other suitable bacteria having nematicidal activity are B. amyloliquefaciens IN937a and B. subtilis strain GB03. Bacteria having fungicidal properties may include, but are not limited to, B. pumilus strain GB34. Fungal species exhibiting nematicidal properties may include, but are not limited to, Myrothecium verrucaria, Paecilomyces lilacinus and Purpureocillium lilacinum.

Seed treatment may also include treatment with one or more naturally occurring nematicidal agents, such as a elicitor protein called harpin, which is isolated from specific bacterial plant pathogens such as Erwinia amylovora. An example is Harpin-N-Tek seed treatment technology, available under the N-HibitTM Gold CST brand name.

The seed treatment may also include treatment with one or more species of nodule bacteria found in the roots of leguminous plants, such as the microsymbiotic nitrogen-fixing bacterium Bradyrhizobium japonicum. These bacterial preparations may optionally include one or more lipo-chito-oligosaccharides (LCO), which are nodulation factors (Nods) produced by rhizobia bacteria during the process of initiating nodulation on the roots of leguminous plants. For example, Optimize® brand seed treatment technologies include LCO Promoter Technology™ in combination with bacterial inoculation.

Seed treatment may also include treatment with one or more isoflavones, which may increase the rate of colonization of mycorrhizal fungi on roots. Mycorrhizal fungi improve plant growth by enhancing root uptake of nutrients such as water, sulfates, nitrates, phosphates and metals. Examples of isoflavones include, but are not limited to, genistein, biochanin A, formononetin, daidzein, glycitein, hesperetin, naringenin and pratensein. Formononetin is used as an active ingredient in mycorrhizal fungal inoculation products such as RHC Colonize® AG.

Seed treatment may also include treatment with one or more plant activators that induce systemic resistance in plants following exposure to the pathogen. An example of a plant activator that induces such defense mechanisms is acibenzolar-Smethyl.

Treated seeds typically include a compound of the present invention in an amount of from about 0.1 g to 1 kg per 100 kg of seeds (ie, from about 0.0001 to 1% by weight of the seeds before treatment). The fluid suspension prepared for seed treatment typically includes from about 0.5% to about 70% active ingredient, from about 0.5% to about 30% film-forming adhesive, from about 0.5% to about 20% dispersant, 0% to about 5% thickener, 0% to about 5% pigment and/or colorant, 0% to about 2% defoamer, 0% to about 1% preservative, and 0% to about 75% volatile liquid solvent .

The compounds of this invention can be formulated into a bait composition that is eaten by an invertebrate pest or used in a device such as a trap, a mousetrap, and other similar devices. Such a bait composition may be in the form of granules which include (a) active ingredients, i.e. a biologically effective amount of a compound of Formula 1;

(b) one or more nutrients;

(c) optionally an attractant; and (d) optionally one or more wetting agents.

Of note are granules or bait compositions that include about 0.001-5% active ingredients, about 40-99% food materials and/or attractant, and optionally about 0.05-10% wetting agents that are effective in controlling soil dwellers. invertebrate pests at very low application rates, particularly at doses of the active ingredient that are lethal by ingestion rather than by direct contact. Some food materials can function as both a food source and an attractant. Food materials include carbohydrates, proteins and fats. Examples of food materials are finely ground vegetable matter, sugar, starches, animal fat, vegetable oil, yeast extracts and milk solids. Examples of attractants are odorants and flavoring agents, such as fruit or plant extracts, flavoring agent or other animal or plant components, pheromones or other agents used to attract the desired invertebrate pest. Examples of humectants, i.e. moisture retaining substances are glycols and other polyols, glycerin and sorbitol. Of note is a bait composition (and a method of using such bait composition) used to control at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. An invertebrate pest control apparatus may include the present bait composition and a housing adapted to receive said bait composition, wherein the housing has at least one opening sized to allow the invertebrate pest to pass through the opening, whereby the invertebrate pest can receive accessing said bait composition from a location outside the housing, and wherein the housing is further adapted to be located at or adjacent to a site of potential or known invertebrate pest activity.

One embodiment of the present invention relates to a method for controlling invertebrate pests, comprising diluting a pesticide composition of the present invention (a compound of Formula 1 formulated together with surfactants, solid diluents and liquid diluents, or a formulated mixture of a compound of Formula 1 and at least one other pesticide) with water, optionally adding an excipient to form a diluted composition and contacting the invertebrate pest or its habitat with an effective amount of said diluted composition.

Although a spray composition formed by diluting a sufficient concentration of the present pesticide composition with water may provide sufficient effectiveness in controlling invertebrate pests, separately formulated auxiliary products may also be added to spray tank mixtures. These additional excipients are commonly referred to as spray adjuvants or tank mix adjuvants and include any substance that is mixed in the sprayer tank for the purpose of improving the performance of the pesticide or altering the physical properties of the spray mixture. Excipients may be surfactants, emulsifiers, petroleum-based vegetable oils, crop seed oils, acidulants, buffers, thickeners or defoamers. Excipients are used to enhance effectiveness (e.g., bioavailability, adhesion, penetration, coating uniformity, and duration of protection) or to minimize or prevent spray application problems associated with incompatibility, foaming, carryover, evaporation, volatilization, and degradation. To obtain optimal performance characteristics, additional substances are selected based on the properties of the active ingredient, drug and target object (eg, crops, insect pests).

Among the excipients for spray compositions, oils including oils for addition to herbicide preparations, oil concentrates for addition to herbicide preparations, plant seed oil concentrates and methylated plant seed oil concentrates are most often used to improve the effectiveness of pesticide application, possibly due to the fact that they contribute to a more even and uniform deposition of sprayed drugs. In situations where phytotoxicity potentially caused by oils or other water-immiscible liquids must be taken into account, spray compositions prepared from the composition of the present invention will generally not contain oil-based excipients. However, in situations where phytotoxicity caused by oil-based excipients contained in spray compositions is not commercially significant, spray compositions prepared from the composition of the present invention may also contain oil-based excipients that can potentially increase control effectiveness with invertebrate pests, and also increase the length of time required after application of the drug before rain for the drug to continue to be effective.

Products identified as oils for addition to herbicidal formulations typically contain 95 to 98% paraffinic or naphtha-based petroleum oil and 1 to 2% one or more surfactants that act as emulsifiers. Products identified as oil concentrates for addition to herbicide formulations typically contain 80 to 85% emulsifiable petroleum-based oil and 15 to 20% nonionic surfactants. Products that are correctly identified as plant seed oil concentrates typically contain 80 to 85% vegetable oil (i.e. seed or fruit oil, most commonly cotton, flax, soybean or sunflower seed) and 15 to 20% non-ionic surfactants. The performance characteristics of the excipient can be improved by replacing vegetable oil with fatty acid methyl esters, which are usually obtained from vegetable oils.

Examples of methylated seed oil concentrates include MSO® Concentrate (UAP-Loveland Products, Inc.) and Premium MSO Methylated Spray Oil (Helena Chemical Company).

The amount of excipients added to the spray mixtures typically does not exceed about 2.5% by volume, and most often the amount is from about 0.1% to about 1% by volume. The specific consumption of auxiliary substances added to spray mixtures is usually approximately 1 to 5 l/ha. Typical examples of excipients for spray mixtures include Adigor® (Syngenta) 47% methylated canola oil in liquid hydrocarbons, Silwet® (Helena Chemical Company) polyalkylene oxide modified heptamethyltrisiloxane and Assist® (BASF) 17% surfactant blend in 83% mineral oil paraffin based.

The compounds of this invention can be used without other excipients, but most commonly a formulation is used comprising one or more active ingredients with suitable carriers, diluents and surfactants, and often in combination with a feed depending on the intended end use. One method of application involves spraying an aqueous dispersion or solution of the compound of the present invention in refined oil. Combinations with spray oils, spray oil concentrates, adhesives, excipients, other solvents and piperonyl butoxide often enhance the activity of the compound. For non-agricultural applications, such spray formulations may be applied from a spray container such as a can, flask or other container, or by use of a pump or by release from a pressurized container, such as a pressurized aerosol can. Such spray compositions can take various forms, for example, aerosols, mists, foams, vapors or smoke. Therefore, such spray compositions may additionally include propellants, foaming agents, etc., depending on the particular case. Of note is a spray composition comprising a biologically effective amount of a compound or composition of the present invention and a carrier. One embodiment of such a spray composition includes a biologically effective amount of a compound or composition of the present invention and a propellant. Typical propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the above. Of note is a spray composition (and a method of using such spray composition released from a spray container) used to control at least one invertebrate pest selected from the group consisting of mosquitoes, midges, fly flies, horseflies, horseflies, wasps, folded winged wasps, hornets, ticks, spiders, ants, mosquitoes and other similar insects, including individually or in combinations.

The following tests demonstrate the effectiveness of the compounds of this invention in controlling specific agricultural pests. Effective control means inhibition of the development of an invertebrate pest (including mortality), which leads to a significant reduction in the food it absorbs. However, the pest control provided by the compounds is not limited to these pest species. See Rating Tables A-G for connection descriptions.

Examples of testing the biological activity of compounds according to the invention

Preparation and spray method for tests A-H.

Test compounds were prepared using a solution containing 10% acetone, 90% water and 300 ppm Activator 90® nonionic surfactant (Loveland Products, Loveland, Colorado, USA). The prepared compounds were applied in a volume of 1 ml of liquid through a nozzle located 1.27 cm above the top of each test object. The test compounds were sprayed at the specified flow rates, and each test was repeated three times.

Test A.

To evaluate the control of cabbage moth (Plutella xylostella (L.)), the test object consisted of a small open container containing a mustard plant in a 12-14 day development phase. This plant was pre-infected with ~50 newborn larvae, which were transferred to the test site on coarse corn kernels using an inoculator. The larvae moved throughout the test plant after being transferred to the test object.

Test compounds were prepared and sprayed at concentrations of 250, 50, 10 and 2 ppm. After spraying the prepared test compound, each test object was dried for 1 hour and then covered with a black lid with punched holes on top. The test objects were kept for 6 days in a growth chamber at 25°C and 70% relative humidity. Damage due to plant feeding was then visually assessed based on the foliage eaten, and larval mortality was assessed.

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Of the Formula 1 compounds tested at 250 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality): 1, 2, 10, 34, 35, 39 and 40.

Of the Formula 1 compounds tested at 50 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality): 1, 2, 10, 34, 35, 39 and 40.

Of the Formula 1 compounds tested at 10 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality): 1, 2, 3, 4, 5, 6 , 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 , 33, 34, 35, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 65, 70, 71, 72, 73, 74, 75, 76, 77, 78 and 79.

Of the compounds of Formula 1 tested at 2 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality): 1, 2, 3, 4, 5, 6 , 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 26, 27, 28, 29, 30, 31, 33, 34, 35 , 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 55, 56, 58, 59, 60, 61, 63, 65, 70, 71, 72, 73 , 74, 75, 76, 77, 78 and 79.

Test B.

To evaluate control of fall armyworm (Spodoptera frugiperda (J.E. Smith)), the test object consisted of a small open container containing a 4-5 day old maize plant. This plant was previously infested with 10-15 1-day-old larvae on a piece of insect food.

Test compounds were prepared and sprayed at 250, 50, 10 and 2 ppm. After spraying the prepared test compound, the test objects were kept in a growth chamber for 6 days at 25°C and 70% relative humidity. Damage due to plant feeding was then visually assessed based on the foliage eaten, and larval mortality was assessed.

Of the compounds of Formula 1 tested at 250 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality: 1, 2, 10, 34, 35, 39 and 40.

Of the compounds of Formula 1 tested at 50 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality: 1, 2, 10, 34, 35, 39 and 40.

Of the compounds of Formula 1 tested at 10 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality: 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 27, 28, 29, 30, 31, 33, 34, 39, 41, 43, 44, 45, 46, 47, 48, 49, 50, 52, 55, 58, 59, 60, 61, 63, 65, 70, 71, 72, 73, 74, 75, 76, 77, 78 and 79.

Of the compounds of Formula 1 tested at 2 ppm, the following compounds provided very good to excellent levels of control effectiveness (40% or less damage due to plant feeding and/or 100% mortality: 1, 2, 3, 4, 8, 10, 11, 13, 15, 16, 18, 19, 20, 33, 34, 39, 43, 46, 49, 50, 59, 60, 61, 63, 65, 70, 71, 74, 76, 78 and 79.

Test C.

To evaluate control of corn leafhopper (Peregrinus maidis (Ashmead)) by contact and/or systemically, the test item consisted of a small open container containing a 3-4 day old corn plant. Pure quartz sand was added on top of the soil, then the test compound was applied.

Test compounds were prepared and sprayed at 50 ppm. After spraying the prepared test compound, test objects were dried for 1 hour and then pre-infested with ~15-20 larvae (18-21 days old). Each test object was covered with a black lid with punched holes on top, and the test objects were kept for 6 days in a growth chamber at 22-24°C and 50-70% relative humidity. Each test item was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 50 ppm, the following compounds resulted in at least 80% insect mortality: 11, 44, 46, 60, 61 and 63.

Test D

To evaluate the control of potato leafhopper (Empoasca fabae (Harris)) by contact and/or systemically, the test object consisted of a small open container containing the Soleil legume plant at 5-6 days of development (first leaf emergence). Pure quartz sand was added on top of the soil and one of the first leaves was removed, then the test compound was applied.

Test compounds were prepared and sprayed at 250, 50, 10 and 2 ppm. After spraying the prepared test compound, the test objects were dried for 1 hour and then pre-infested with 5 potato leafhoppers (adults 18-21 days old).

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The test object was covered with a black lid with punched holes on top, and the test objects were kept for 6 days in a growth chamber at 20°C and 70% relative humidity. Each test item was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following compounds resulted in at least 80% insect mortality: 1, 2, 10, 34, 35, 39 and 40.

Of the compounds of formula 1 tested at 50 ppm, the following compounds resulted in at least 80% insect mortality: 1, 2, 3, 4, 5, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 27, 31, 33, 34, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 55, 58, 59, 60, 61, 63, 65, 70, 71, 72, 75, 76, 78 and 79.

Of the compounds of formula 1 tested at 10 ppm, the following compounds resulted in at least 80% insect mortality: 3, 4, 8, 10, 11, 13, 14, 15, 16, 18, 19, 20, 27, 33, 41, 43, 44, 47, 48, 49, 50, 52, 58, 59, 60, 61, 63, 65, 70, 71, 72, 75, 76, 78, 79.

Of the compounds of Formula 1 tested at 2 ppm, the following compounds resulted in at least 80% insect mortality: 15, 16, 18, 20, 33, 61 and 63.

Test E.

To evaluate the control of green peach aphids (Myzus persicae (Sulzer)) by contact and/or systemically, the test object consisted of a small open container containing a radish plant at a 12-15 day development stage. The plant was pre-infested by placing 30-40 aphids on a leaf of the test plant on a piece of leaf cut from the crop plant (cut leaf method). Aphids moved across the test plant as a piece of leaf dried. After preliminary contamination, a layer of sand was applied to the soil of the test object.

Test compounds were prepared and sprayed at 250, 50 and 10 ppm. After spraying the prepared test compound, each test object was dried for 1 hour, and then the top was covered with a black lid with punched holes. The test objects were kept for 6 days in a growth chamber at 19-21°C and 50-70% relative humidity. Each test item was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following compounds resulted in at least 80% insect mortality: 2, 10, 34 and 35.

Of the compounds of formula 1 tested at 50 ppm, the following compounds resulted in at least 80% insect mortality: 3, 4, 8, 11, 18, 19, 20, 33, 34, 35, 41, 44, 50, 58, 60, 61, 63 and 70.

Of the compounds of Formula 1 tested at 10 ppm, the following compounds resulted in at least 80% insect mortality: 61 and 63.

Test F.

To evaluate the control of melon or cotton aphids (Aphis gossypii (Glover)) by contact and/or systemically, the test object consisted of a small open container containing an okra plant at the 5-day stage of development. This plant was previously infested with 30-40 insects on a piece of leaf using the cut leaf method, and a layer of sand was applied to the soil of the test object.

Test compounds were prepared and sprayed at 250, 50 and 10 ppm. After spraying, the test objects were kept in a growth chamber for 6 days at 19°C and 70% relative humidity. Each test item was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following compounds resulted in at least 80% insect mortality: 1, 2, 10, 34, 35 and 39.

Of the compounds of formula 1 tested at 50 ppm, the following compounds resulted in at least 80% insect mortality: 3, 4, 8, 10, 11, 16, 18, 19, 20, 22, 33, 34, 35, 41, 44, 46, 47, 49, 50, 55, 58, 59, 60, 61, 63 and 70.

Of the compounds of Formula 1 tested at 10 ppm, the following compounds resulted in at least 80% insect mortality: 19, 20, 33, 41, 44, 59, 60, 61, 63 and 70.

Test G.

To evaluate the control of cotton whitefly (Bemisia tabaci (Gennadius)) by contact and/or systemically, the test object consisted of a small open container containing a cotton plant at the 12-14 day stage of development. Before application by spraying, both cotyledons were removed from the plant, leaving one true leaf for study. Adult whiteflies were allowed to lay eggs on the plant and then removed from the test object. Cotton plants infested with at least 15 eggs were subjected to a spray treatment test.

Test compounds were prepared and sprayed at 250, 50 and 10 ppm. After spraying, the test objects were dried for 1 hour. The cylinders were then removed and the objects were placed in a growth chamber and kept for 13 days at 28°C and 50-70% relative humidity. Each test item was then visually assessed for insect mortality.

Of the compounds of formula 1 tested at 250 ppm, the following compounds resulted in

Claims (14)

led to at least 70% insect mortality: 2, 34 and 40. Of the compounds of formula 1 tested at 50 ppm, the following compounds resulted in at least 70% insect mortality: 3, 8, 11, 15, 17, 18, 19, 20, 33, 34, 41, 42, 44, 46, 49, 55, 58, 60, 61, 63 and 70. Of the compounds of formula 1 tested at 10 ppm, the following compounds resulted in at least 70% insect mortality: 8, 11, 18, 19, 20, 33, 34, 42, 49, 61 and 63. Of the compounds of Formula 1 tested at 2 ppm, the following compounds resulted in at least 70% insect mortality: 18, 20, 33 and 63. Test N. To evaluate contact and/or systemic control of Western flower thrips (Frankliniella occidentals (Pergande)), the test item consisted of a small open container containing a Soleil legume plant at a 5-7 day development stage. Test compounds were prepared and sprayed at 250, 50, 10 and 2 ppm. After sprinkling, test objects were dried for 1 h, and then ~60 thrips (adults and larvae) were added to each object. The top was covered with a black lid with punched holes, and the test objects were kept for 6 days at 25°C and 45-55% relative humidity. Each test item was then visually assessed for plant damage and insect mortality. Of the Formula 1 compounds tested at 250 ppm, the following compounds provided very good to excellent levels of control effectiveness (30% or less plant damage and/or 100% mortality): 1, 2, 10, 34, 35, 39 and 40. Of the Formula 1 compounds tested at 50 ppm, the following compounds provided very good to excellent levels of control effectiveness (30% or less plant damage and/or 100% mortality: 1, 10, 34, 35, 39, and 40. Of the compounds of Formula 1 tested at 10 ppm, the following compounds provided very good to excellent levels of control effectiveness (30% or less plant damage and/or 100% mortality: 1, 3, 4, 5, 7, 8, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 31, 33, 34, 39, 41, 43, 44, 45 , 46, 47, 48, 49, 50, 58, 59, 60, 61, 63, 65, 70, 71, 72, 73, 74, 75, 76, 78 and 79. Of the compounds of Formula 1 tested at 2 ppm, the following compounds provided very good to excellent levels of control effectiveness (30% or less plant damage and/or 100% mortality: 3, 4, 8, 10, 11, 13, 14, 16 , 19, 20, 22, 26, 27, 33, 34, 39, 43, 44, 46, 47, 50, 59, 60, 61, 63, 70, 71, 72, 73, 74, 75, 76, 78 and 79. CLAIM 1. Compound of formula 1 where J represents C ₂ -C ₄ alkyl substituted with one cyano group or cyclopropyl; or J represents R ^1a represents Cl or CF ₃ ; R ^1b represents H or Cl; R ² represents C1-C ₄ alkyl, unsubstituted or substituted with substituents selected from cyano, nitro and OR ⁹ ; - 84 043836 R ³ represents H or C1-C4 alkyl, unsubstituted or substituted with substituents selected from cyano, nitro and OR ⁹ ; R ⁴ represents H or C1-C4 alkyl; R ⁵ represents H or C1-C4 alkyl; R ⁶ represents H or C1-C4 alkyl; R ⁷ represents H, C1-C4 alkyl or C1-C4 haloalkyl; X represents -O- or -C(O)-; R ⁸ represents H, C1-C4 alkyl or C1-C4 haloalkyl; R ⁹ represents H or C1-C4 alkyl; R ¹⁴ represents H or C1-C4 alkyl, unsubstituted or substituted with substituents selected from cyano, nitro and OR ⁹ ; R ¹⁵ represents H or C1-C4 alkyl; R ¹⁶ represents C1-C4 alkyl or C1-C4 haloalkyl; Q represents pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyloxazolyl, thiazolyl, isoxazolyl , isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl or 1,3,4-thiadiazolyl , each of which is unsubstituted or substituted with substituents independently selected from cyano, nitro, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio , C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, _C2 - _C5 alkoxycarbonyl, _C2 - _C5 alkylaminocarbonyl and C3-C5 dialkylaminocarbonyl. 2. A compound according to claim 1, wherein J is J-l, J-2 or J-5. 3. Connection according to claim 2, where R ^la represents O and R ^lb represents O; or R ^la is CF3 and R ^lb is H. 4. A compound according to claim 2, wherein J is J-1. 5. Connection according to claim 4, where R ² represents methyl; R ³ represents H or methyl; And R ⁴ represents H or methyl. 6. A compound according to claim 2, wherein J is J-2. 7. Connection according to claim 6, where R ⁵ represents H or methyl; And Q represents pyridinyl or pyrimidinyl. 8. The connection according to claim 7, where J-2 represents R ⁵ J-2a 9. The compound according to claim 2, where J is J-5. 10. Connection according to claim 9, where R ¹⁴ represents H or methyl; And R ¹⁵ represents C1-C4 alkyl. 11. The connection according to claim 10, where J-5 is R ¹⁴ J-5a 12. A composition for controlling invertebrate pests, comprising a compound according to claim 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. 13. A method of controlling an invertebrate pest in agrotechnical applications, including contacting the invertebrate pest or its habitat with a biologically effective amount of a compound according to π. 1. 14. Treated seeds treated with the compound according to claim 1 in an amount from 0.0001 to 1% by weight of the seeds before treatment. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky lane, 2