CRYSTALLINE POLYMORPH, COMPOSITION, METHOD FOR CONTROLING AN INVERTED PEST AND USE OF POLYMORPH

专利摘要:
crystalline polymorph, composition, method for controlling an invertebrate pest and use of the polymorph is presented as a solid form of 4- [5- [3-chloro-5- (trifluoromethyl) phenyl] -4,5-dihydro-5- ( trifluoromethyl) -3-isoxazolyl] -N- [2-oxo-2 - [(2,2,2-trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide (compound 1). Also disclosed are compositions containing a solid form of compound 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a solid form of compound 1 or a composition containing a solid form. of compound 1.
公开号:BR112012030151B1
申请号:R112012030151-9
申请日:2011-05-19
公开日:2019-10-08
发明作者:Martin James Currie
申请人:E.I. Du Pont De Nemours And Company；
IPC主号:

专利说明:

“CRYSTALLINE POLYMORPH, COMPOSITION, METHOD TO CONTROL AN INVERTEBRATED PEST AND USE OF THE POLYMORPH”
Field of the Invention [001] This invention relates to a solid form of 4- [5- [3-chloro5- (trifluoromethyl) phenyl] -4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [2-oxo-2 [(2,2,2-trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide.
Background of the Invention [002] The solid state of chemical compounds can be amorphous (i.e., no long-range order at the positions of atoms) or crystalline (i.e., atoms arranged in an orderly repetition pattern). Although only one crystal form is known for the solid state of many compounds, polymorphs have been found for some compounds. The term polymorph refers to a particular crystal form (i.e., crystal lattice structure) of a chemical compound that can exist in more than one solid crystal form. Polymorphs can differ in chemical and physical (i.e., physiochemical) properties such as crystal shape, density, stiffness, color, chemical stability, melting point, hydroscopicity, suspension and dissolution rate, and such biological properties, such as biological availability .
[003] The prediction of physiochemical properties, such as a melting point for a crystal form or crystal forms in which the solid state of a chemical compound can exist, remains impossible. Furthermore, even the prediction of whether the solid state of a compound may be present in more than one crystal form is not possible.
[004] PCT patent publication WO 09/002809 discloses 4- [5 [3-chloro-5- (trifluoromethyl) phenyl] -4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M - [2oxo-2 - [(2,2,2-trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide and methods for its preparation, as well as the utility of this compound as an agent of
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2/81 invertebrate pest control. A new solid form of this compound has been found.
Brief Description of the Invention [005] This invention relates to a solid form of 4- [5- [3-chloro5- (trifluoromethyl) phenyl] -4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl ] -N- [2-oxo-2 [(2,2,2-trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide (compound 1). More particularly, this invention is directed to a crystalline polymorph of compound 1 called Form B characterized by a powder X-ray diffraction pattern that has at least the reflection portions 2Θ 17,433, 18,586, 20,207, 20,791,21,41,22,112 , 23,182, 24,567 and 27,844.
[006] This invention also relates to compositions containing a solid form of compound 1 and methods for controlling an invertebrate pest which comprises bringing the invertebrate pest or its environment into contact with a biologically effective amount of a solid form of compound 1 or a composition containing a solid form of compound 1.
Brief Description of the Drawings [007] Figure 1 shows the powder X-ray diffraction patterns of polymorph and pseudopolymorph crystal forms of compound 1 showing the absolute intensity count recorded against 2Θ reflection positions.
Detailed Description of the Invention [008] As used herein, the terms comprise, comprise, include, include, have, have, contain or contain or any other variation thereof are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to just those elements, but may include other elements not expressly mentioned or inherent in such a composition, process, method, article or apparatus . Furthermore, the
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3/81 unless expressly stated otherwise, or refers to one or inclusive and not one or exclusive. For example, a condition A or B is satisfied by any of the following: A 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).
[009] In addition, the indefinite articles one and one preceding an element or component of the invention are intended to be non-restrictive in relation to the number of cases (i.e., occurrences) of the element or component. Therefore, one or one should be read as including one or at least one, and the form of the word in the singular of the element or component also includes the plural unless the number is obviously intended to be the singular.
[010] Modalities of the present invention include:
[011] Mode 1. The crystalline solid form of 4- [5- [3-chloro-5 (trifluoromethyl) phenyl] - 4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [ 2-oxo-2 - [(2,2,2trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide where at least 90% of the solid form is polymorph Form B.
[012] Mode 2. The crystalline solid form of 4- [5- [3-chloro-5 (trifluoromethyl) phenyl] - 4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [ 2-oxo-2 - [(2,2,2trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide where at least 80% of the solid form is polymorph Form B.
[013] Mode 3. The crystalline solid form of 4- [5- [3-chloro-5 (trifluoromethyl) phenyl] - 4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [ 2-oxo-2 - [(2,2,2trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide where at least 70% of the solid form is polymorph Form B.
[014] Mode 4. The crystalline solid form of 4- [5- [3-chloro-5 (trifluoromethyl) phenyl] - 4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [ 2-oxo-2 - [(2,2,2trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide where at least 60% of the
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4/81 solid form is polymorph Form B.
[015] Modality 5. A composition comprising compound 1, with compound 1 being present in at least 90% polymorph Form B, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents , said composition additionally optionally comprising at least one additional biologically active compound or agent.
[016] Modality 6. A composition comprising compound 1, in which compound 1 is present in at least 80% polymorph Form B, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition further optionally comprising at least one additional biologically active compound or agent.
[017] Modality 7. A composition comprising compound 1, in which compound 1 is present in at least 70% polymorphic Form B, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, being that said composition optionally further comprises at least one additional biologically active compound or agent.
[018] Mode 8. A composition comprising compound 1, in which compound 1 is present in at least 60% polymorph Form B, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition further optionally comprising at least one additional biologically active compound or agent.
[019] The crystalline polymorph of compound 1 designated Form B, and any of the modalities of the invention, can be used to protect an animal against an invertebrate pest by administering the compound
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5/81 to the animal.
[020] Therefore, the invention is understood to include the crystalline polymorph of compound 1 designated Form B, or any embodiments of the invention for use as an animal medicine, or, more particularly, a parasitic animal medicine. The drug can be in any technique recognized dosage forms including oral, topical or parenteral dosage forms.
[021] The invention is also understood to include the use of the crystalline polymorph of compound 1 designated Form B, or any embodiment of the invention for the manufacture of a medicament for the protection of an animal from an invertebrate pest. The drug can be in any technique recognized dosage forms including oral, topical or parenteral dosage forms.
[022] The invention is also understood to include the crystalline polymorph of compound 1 designated Form B, or any embodiments of the invention, packaged and presented for the protection of an animal from an invertebrate pest. The compounds of the invention can be packaged and presented as oral, topical or parenteral dosage forms.
[023] The invention is also understood to include a process for the manufacture of a composition to protect an animal from an invertebrate parasitic pest characterized by the fact that the crystalline polymorph of compound 1 designated Form B, or any modalities of the invention, is mixed at least one vehicle. The compounds of the invention can be packaged and presented in any dosage forms recognized in the art including oral, topical or parenteral dosage forms.
[024] Compound 1 is 4- [5- [3-chloro-5- (trifluoromethyl) phenyl] -4,5-diPetition 870190077112, from 08/09/2019, pg. 15/95
6/81 hydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [2-oxo-2 - [(2,2,2-trifluoroethyl) amino] ethyl] -1naphthalenecarboxamide and has the following chemical structure:
i [025] Compound 1 can exist in more than one crystal form (i.e., polymorph). A person skilled in the art will find that a polymorph of compound 1 can exhibit beneficial effects (for example, suitability for preparing useful formulations, improved biological performance) over another polymorph or a mixture of polymorphs of the same compound. Regarding chemical stability, filterability, solubility, hygroscopicity, melting point, solid density and fluidity, they can have a significant effect on the development of production methods and formulations, and the quality and effectiveness of plant treatment agents.
[026] The molecular structure of compound 1 can exist as two distinct stereoisomers (ie, enantiomers). The present invention encompasses a racemic mixture of compound 1 that comprises equal amounts of the two possible enantiomers.
[027] It has now been found that the solid state of compound 1 is preparable in more than one solid form. These solid forms include an amorphous solid form, in which there is no long-range order in the positions of the molecules (for example, foams and glasses). These solid forms also include crystalline forms, in which constituent molecules are arranged in an orderly repetition pattern that extends across all three spatial dimensions. The term polymorph refers to a particular crystalline form of a chemical compound that can exist in more than one crystal structure (for example,
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7/81 example, truss type) in solid state. The crystalline forms of compound 1 in this invention refer to modalities that include a single polymorph (i.e., single crystalline form) and to modalities that include a mixture of polymorphs (i.e., different crystalline forms). Polymorphs can differ in such chemical, physical and biological properties, such as crystal shape, density, stiffness, color, chemical stability, melting point, hygroscopicity, suspension, dissolution rate and biological availability. A person skilled in the art will appreciate that a polymorph of compound 1 may exhibit beneficial effects (for example, suitability for preparing useful formulations, improved biological performance) over another polymorph or a mixture of polymorphs of compound 1. Differences from chemical stability, filterability, solubility, hygroscopicity, melting point, solid density and fluidity can have a significant effect on the development of production methods and formulations, and the quality and effectiveness of plant treatment agents. The preparation and isolation of particular compound 1 polymorphs has now been achieved.
[028] Most polymorphs in compound 1 are pseudopolymorphs (different types of crystal that are a result of hydration or solvation). A solvate is a crystal form with a stoichiometric or non-stoichiometric amount of solvent. A hydrate is a solvate with water as the solvent.
[029] A variety of experimental procedures were conducted to explore the crystalline solid profile for compound 1. Crystalline solids were generated with eight unique X-ray powder diffraction patterns (XRPD) as well as amorphous X-ray material. of XRPD for the various solids are shown in figure 1. Most solids are solvates or hydrates. Solids known to be composed of a single phase are called 'Form X' and solids are called 'Standard X'
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8/81 can represent a mixture of solid forms. Two polymorphs were identified (Form A and Form B). The crystalline solid profile experiments can be summarized as shown in scheme 1.
Layout 1
Standard C EtOAc solvate
amorphous x-rays
Standard F nPrOH solvate 11
IPrOH H Solvate Standard
Standard ACN solvate G [030] Compound 1 can exist as an amorphous solid. The standard
XRPD for the amorphous solid compound 1 shows no significant signal and is therefore readily distinguished from the standards of crystalline compound 1.
[031] The amorphous form of compound 1 can also be characterized by cyclic differential scanning calorimetry. As described in characterization example 2, the glass transition temperature of an amorphous form of compound 1 was determined to be about 72 ° C.
The amorphous form of compound 1 is physically unstable and readily crystallized in its pure solid form (shown in the characterization example
3).
[032] The amorphous solid form was prepared by melting the polymorph
Form A and then sudden cooling in a dry ice / acetone bath.
[033] A crystalline polymorph form of compound 1 is designated as Form A. This solid form is a desolvated solvate. A desolvated solvate is formed from a crystal form of the solvate (which
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9/81 contains compound 1 and solvent molecules) that lost the solvent molecules through channels in the crystal under vacuum and heating conditions, resulting in a desolvated crystal form with the same molecular package as the relative solvate crystal form . Form A can be characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC).
[034] The powder X-ray diffraction pattern of the Form 1 polymorph of compound 1 is shown in figure 1. The corresponding 2Θ values are tabulated in Table 1 of the characterization example 1. The Form A polymorph of compound 1 can be identified by a powder X-ray diffraction pattern that has at least 2Θ reflection portions
[035] The Form A polymorph of compound 1 can also be characterized by differential scanning calorimetry. DSC indicates that the melting point of the Form A polymorph is about 113 ° C. The details of a DSC experiment are provided in characterization example 2. The polymorph Form A is non-hygroscopic and a desolvated solvate related to the solid of Pattern G, which is the acetonitrile solvate of Form A (shown in characterization example 3 and 5).
[036] The polymorph Form A of compound 1 can be prepared by the procedure described in PCT patent publication WO 09/025983 (for example, see synthesis example 7). The recrystallization of the solid product
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10/81 raw acetonitrile usually yields a mixture of the solid of Standard G and Form A of compound 1. The conversion of the recrystallized product from mixed solvate / desolvate to Form A can be achieved by vacuum drying (50 ° C, 4 24 hours).
[037] A second form of crystalline polymorph of compound 1 is called Form B. This solid form is a hydrate.
[038] The X-ray diffraction pattern of Form B polymorph powder of compound 1 is shown in figure 1. The corresponding 2Θ values are tabulated in Table 2 of the characterization example 1. The Form B polymorph of compound 1 can be identified by a powder X-ray diffraction pattern that has at least 2Θ reflection positions
[039] The Form B polymorph of compound 1 can also be characterized by differential scanning calorimetry. DSC indicates that the melting point of the Form B polymorph is about 147 ° C. The details of a DSC experiment are provided in characterization example 2. Polymorph Form B is physically stable and hydrated in its pure solid form (shown in characterization example 3). The higher melting point of the Form B polymorph is advantageous for use in formulations that involve grinding the active ingredient or a slurry of the active ingredient in liquid vehicles.
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11/81 [040] Slow recrystallization of Form A from methanol / water provided a first purified culture of Form B crystals, as described in Preparation Example 1. The Form B polymorph was also produced by suspending the Form A polymorph in methanol / water (1: 2) at 60 ° C for 3 days and then cooling to 22 ° C and filtration. The efficient large-scale preparation of Form B is facilitated by adding the Form B seed crystals prepared previously to the solution of compound 1 in methanol / water to cause the product to crystallize in polymorph Form B (see preparation examples 2 and 3) .
[041] The relative stability of the polymorphic Forms A and B of compound 1 was characterized with interconversion slurry experiments (see characterization example 4). The relative physical stability of the solid forms of compound 1 is dependent on the solvent used in the slurry experiment. The Standard G solid is the most stable solid form in acetonitrile. The Form A polymorph is a solid form relative to the Pattern G solid in acetonitrile and is sometimes formed in a mixture with Pattern G solid from acetonitrile. Standard G solid can be converted to Form A polymorph by desolvation by vacuum drying. Polymorph Form B is the most stable solid form in organic solvent / water mixtures especially in methanol / water.
[042] Another crystalline solid form of compound 1 was designated a Pattern C solid. The Pattern C solid was characterized by X-ray powder diffraction and differential scanning calorimetry. The powder X-ray diffraction pattern of Pattern C of compound 1 is shown in the figure
1. By DSC, the Pattern C solid exhibited a unique endotherm at 101 ° C accompanied by a 9.4% weight loss. Ethyl acetate was detected in the ¹ H NMR of the material which indicates that the solid is a solvate of
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12/81 ethyl acetate. The Pattern C solid was prepared by dissolving compound 1 in ethyl acetate at 80 ° C and then slowly cooling to 22 ° C and filtration.
[043] Another crystalline solid form of compound 1 was designated a Pattern D solid. The Pattern D solid was characterized by X-ray powder diffraction and differential scanning calorimetry. The powder X-ray diffraction pattern of Pattern D of compound 1 is shown in figure 1. By DSC, the Pattern D solid exhibited a single endotherm at 105 ° C accompanied by a 5.1% weight loss. Dioxane was detected in the ¹ H NMR of the material which indicates that the solid is a dioxane solvate. The Pattern D solid was prepared by dissolving compound 1 in dioxane and then rapidly evaporating under a flow of nitrogen gas at 22 ° C.
[044] Another crystalline solid form of compound 1 was called Pattern E solid. Pattern E solid was characterized only by X-ray powder diffraction (Figure 1). The Pattern E solid was prepared by dissolving compound 1 in isopropyl alcohol and then evaporating rapidly under a flow of nitrogen gas at 22 ° C.
[045] Another crystalline solid form of compound 1 was designated a Pattern F solid. The Pattern F solid was characterized by X-ray powder diffraction and differential scanning calorimetry. The powder X-ray diffraction pattern of Pattern F of compound 1 is shown in figure 1. By DSC, the Pattern F solid exhibited a single endotherm at 87 ° C accompanied by a 10% weight loss. 1-Propanol was detected in the ¹ H NMR of the material, indicating that the solid is a 1-propanol solvate. The Pattern F solid was prepared by suspending compound 1 in 1-propanol / water (9: 1) at 40 ° C for 4 days and then cooling to 22 ° C and filtration.
[046] Another crystalline solid form of compound 1 was designated as the Pattern G solid. The Pattern G solid was characterized by powder diffraction
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13/81 X-ray and differential scanning calorimetry. The powder X-ray diffraction pattern of Pattern G of compound 1 is shown in figure 1. By DSC, the solid of Pattern G exhibited a single endotherm at 73 ° C accompanied by a 7% weight loss. Acetonitrile was detected in the ¹ H NMR of the material, indicating that the solid is an acetonitrile solvate. The Standard G solid was prepared by suspending compound 1 in acetonitrile / water (1: 1) at 40 ° C and then slowly cooling to 22 ° C and filtration. The Standard G solid was consistently prepared from acetonitrile under a variety of recrystallization conditions.
[047] Another solid crystalline form of compound 1 was designated a Pattern H solid. The Pattern H solid was characterized by X-ray powder diffraction and Differential Scanning Calorimetry. The powder X-ray diffraction pattern of Pattern H of compound 1 is shown in Figure 1. By DSC, the Pattern H solid exhibited a single endotherm at 97 ° C accompanied by a 3.5% weight loss. Isopropanol was detected in the ¹ H NMR of the material which indicates that the solid is an isopropanol solvate. The Standard H solid was prepared by suspending compound 1 in iso-propanol / water (1: 1) at 40 ° C for 4 days and then cooling to 22 ° C and filtration.
Characterization Example 1
X-ray powder diffraction experiments [048] X-ray powder diffraction was used to identify the crystallized phases of compound 1. X-ray powder diffraction (XRPD) analysis was performed using an Inel XRG diffractometer -3000 equipped with a CPS (Curved Position Sensitive) detector with a 2Θ range of 120 °. The slots used were 5 mm by 160 pm.
[049] XRPD analysis was also performed using Shimadzu XRD-6000 with Cu (Ko) radiation.
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14/81 [050] The radiation was Cu (Ka), 40 kV, 30 mA. The samples were powders packed in a spinning capillary. Data were collected at 2Θ angles with an equivalent step size of 0.03 degrees and a capture time of 300 seconds.
Table 1
X-ray maximum of 2θ for Polymorph A of compound 1
2Θ 2Θ 2Θ 2Θ 2Θ 2Θ 7,937 18,804 24.97 32,824 40,012 49,287 11,233 19,389 25,672 33,443 41,447 50,022 13,021 20,324 27,492 34,197 43,486 75,486 13.707 21,494 28,262 34,963 44,00114,574 22,263 29,586 36,598 44,67516,196 22,797 30,335 37.908 45,72616,797 23,766 30,969 38,338 47,07917.203 24,218 31,955 39,073 48,453
Table 2
X-ray maximum of 2θ for Polymorph B of compound 1
2Θ 2Θ 2Θ 2Θ 2Θ 2Θ 9,393 17.433 23,182 28,828 39,273 48,635 11,117 18,586 24,567 29,967 40,593 50,172 12,452 20.207 25,103 32.39 42,034 59,533 14.023 20,791 25,853 34.83 43.23714,744 21.41 26,942 36,301 44,90615,361 22,112 27,844 37,286 47,078
Characterization Example 2
Differential Scanning Calorimetry Experiments [051] Differential scanning calorimetry was performed on a Q2000 thermally differential scanning calorimeter. A sample was placed in an aluminum DSC pan and the weight was accurately recorded. The sample cell was equilibrated to 25 ° C or -30 ° C and heated under a nitrogen purge at a rate of 10 ° C / minute to a final temperature of 250 ° C. Indian metal was used as the calibration standard.
[052] A cyclic DSC experiment was also carried out using a Q2000 thermal scanning differential scanning calorimeter. An
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15/81 sample was placed in an aluminum DSC pan and the weight was accurately noted. The sample cell was equilibrated to 25 ° C and heated under a nitrogen purge at a rate of 10 ° C / minute to a final temperature of 140 ° C, quickly cooled to -40 ° C and reheated to a final temperature of 250 ° C ° C. Indian metal was used as the calibration standard. The glass transition temperature (Tg) of the amorphous compound 1 was determined to be 72 ° C at half height.
[053] The DSC curve for the Form 1 polymorph of compound 1 was observed to exhibit an acute endotherm at 113 ° C.
[054] The DSC curve for Form B polymorph of compound 1 was observed to exhibit an acute endotherm at 147 ° C.
Characterization Example 3 Stability Experiments for Solid Forms of Compound 1 [055] The physical stability of the amorphous material was characterized. Amorphous compound 1 was steam tensioned under acetonitrile at 25 ° C for 2 days, resulting in the formation of irregular crystal fragments that were determined to be the Standard G material by XRPD. The amorphous compound 1 was also suspended in methanol water (1: 1) for 5 days at 60 ° C, resulting in irregular crystal fragments determined to be Form B by XRPD. This indicates that the amorphous solid was physically and readily crystallized.
[056] The physical stability of the Form A polymorph has been characterized. Samples of Form A exposed to 5 to 95% relative humidity at 25 ° C (5 hours) showed only a negligible change in weight, which indicates that the material is not hygroscopic.
[057] The physical stability of the Form B polymorph has been characterized. Form B samples were tensioned under 75% relative humidity (40 ° C) and 60% relative humidity (25 ° C) for 1 month also remained
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16/81 unchanged by XRPD, indicating that Form B is stable under the conditions tested.
Characterization Example 4 Relative Stability Experiments for Polymorph Form A and Form B [058] Slurry interconversion experiments were performed in a variety of solvents at different temperatures. Sufficient amounts of compound 1 were added to the vial solvents so that the excess solid remained. The mixtures were stirred in sealed flasks at the selected temperature and the solids were isolated by filtration after the selected time and analyzed by XRPD. Compound 1 suspended in acetonitrile for 3 days at 83 ° C or for 8 days at 0 ° C yielded the solid of Standard G. Compound 1 suspended in acetonitrile / water (9: 1) for 3 days at 83 ° C yielded the polymorph Form B. Compound 1 suspended in acetonitrile / water (9: 1) for 8 days at 0 ° C yielded the solid of Standard G.
Characterization Example 5 Vacuum drying experiment [059] The conversion of solid from Standard G to Form A was obtained by vacuum drying (4.80 to 9.07 Pa (36 to 68 mtorr)) of solid from Standard G to 50 ° C for 4 hours. Vacuum drying (6.80 Pa (51 mtorr)) at 70 ° C for 5 hours led the solid of Standard G to become a solid glass.
[060] Compound 1 can be prepared according to the procedures presented in PCT patent publications WO 09/025983) and WO 09/126668.
Preparation example 1
Initial polymorph preparation of Form B of compound 1 [061] Crude compound 1 (10.2 g) was added to boiling methanol (60 ml). Water (12 ml) was added slowly, followed by a small amount of methanol. The heat was then removed, the mixture left
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17/81 to cool briefly, and seed crystals of Form A of compound 1 were then added. The reaction mixture was cooled to room temperature (seed crystals were added again until they no longer dissolved), followed by additional cooling to about 0 ° C for 24 hours. The reaction mixture was filtered to yield 6.0 g of a white solid that melts at 100 to 105 ° C (NMR indicates solvent contamination).
[062] The filtrate obtained above was left to stand for approximately 30 days at room temperature, resulting in the formation of a second crystal culture. The crystals were isolated by filtration, washed with water, briefly air dried, and finally vacuum dried at 50 ° C to yield 2.9 g of a white solid which melts at 144 to 150 ° C.
Preparation example 2
Preparation of polymorph Form B of compound 1 from polymorph Form A [063] Form A of compound 1 (15.3 g) was added to methanol (120 g) and water (50.4 g). The reaction mixture was heated to 40 ° C, and, after 10 minutes, seed crystals of compound 1 (Form B) were added. The reaction mixture was stirred at 35 ° C for 72 hours, cooled to room temperature, and filtered. The isolated solid was then dried in a vacuum oven at 50 to 60 ° C to yield 13.4 g of a soft solid that melts at 147 to 149 ° C.
Preparation example 3
Preparation of polymorph Form B of compound 1 using seed crystals [064] Compound 1 (95 g) was added to methanol (408 g). The mixture was mechanically stirred and heated to 30 ° C to dissolve the solid completely. Water (129 g) was added by dripping until the solution was cloudy and Form B seed crystals were added. The mixture was allowed to cool to 25 ° C and stirred for 3.5 hours. A white solid
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18/81 thick began to precipitate and the mixture was then heated to 45 ° C for 1 hour and cooled to 25 ° C for 45 minutes. The mixture was again heated to 45 ° C for 50 minutes and then cooled to 25 ° C for 40 minutes and filtered. Temperature cycling allows the crystals to grow larger to allow filtration. The crystals were washed with a cold mixture of methanol / water (95 ml 3: 1) and dried in a vacuum oven at 50 ° C for 16 hours to yield 82 g of a white solid that melts at 145 to 148 ° C .
Agronomic Formulation / Utility [065] A compound of this invention will, in general, be used as an invertebrate pest control active ingredient in a composition, that is, formulation, with at least one additional component selected from the group consisting of surfactants, diluents solids and liquid thinners, which serves as a vehicle. Formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, humidity and temperature.
[066] Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspoemulsions) and the like, which can optionally be thick in gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspoemulsion. The general types of non-aqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.
[067] The general types of solid compositions are dust, powders, granules, pellets, nuggets, lozenges, tablets, filled films (including seed coatings) and the like, which can be dispersible in water
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19/81 (humectable) or soluble in water. Films and coatings formed from film forming solutions or fluidizable suspensions are particularly useful for seed treatment. The active ingredient can be (micro) encapsulated and further transformed into a suspension or solidification of form; alternatively, the entire active ingredient formulation can be encapsulated (or overcoated). Encapsulation can control or delay the release of the active ingredient. an emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High strength compositions are primarily used as intermediates for further formulation.
[068] Sprinkling formulations are typically spread in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Sprinkling volumes can vary from about one to a few thousand liters per hectare, but more typically they are in the range of about ten to a few hundred liters per hectare. Sprinkling formulations can be mixed in a tank with water or other suitable medium for foliar treatment by aerial or soil application, or for application in the plant's growth medium. Liquid and dry formulations can be measured directly in drip irrigation systems or measured in the plow during planting. Liquid and solid formulations can be applied to crop seeds and other desirable vegetation as seed treatments before planting to protect developing roots and other underground plant parts and / or foliage through systemic absorption.
[069] Formulations will typically contain effective amounts of active ingredient, diluent and surfactant in the approximate ranges below, which
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20/81 add up to 100 percent by weight.
% by weight Active ingredient Diluent Surfactant Water-dispersible granules, tablets and powders 0.001 to 90 0 to 99,999 0 to 15 Oil dispersions, Aqueous suspensions 1 to 50 40 to 99 0 to 50 Dust 1 to 25 70 to 99 0 to 5 Granules and Pellets 0.001 to 95 5 to 99,999 0 to 15 High strength compositions 90 to 99 0 to 10 0 to 2
[070] Solid thinners include, for example, clays such as bentonite, montmorillonite, atapulgite and kaolin, natural plaster, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (eg 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., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey, USA.
[071] Liquid diluents include, for example, water, N, N-dimethylalkanamides (for example, N, N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkyl pyrrolidones (eg, N-methylpyrrolidone), ethylene glycol, triethylene glycol , propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (for example, white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerin, glycerol triacetate, sorbitol, aromatic hydrocarbons, disaromatized aliphatics , alkylbenzenes, alkylnaphthalenes, ketones, 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, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or i unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, alcohol
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21/81 isodecyl, iso-octadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid thinners also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (eg olive oil, castor oil, flaxseed, sesame, corn (maize), peanuts, sunflower) , grape seed, safflower, cotton seed, soy bean, rapeseed, coconut and palm kernel), animal fats (eg beef tallow, pork, tallow, lard, cod liver oil, fish oil ), and mixtures thereof. Liquid diluents also include alkylated fatty acids (for example, methylated, ethylated, butylated) in which fatty acids can be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, USA, 1950.
[072] The liquid and solid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as surface active agents) generally modify, more often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting, dispersing, emulsifying or defoaming agents.
[073] Surfactants can be classified as non-ionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates, such as alcohol alkoxylates based on natural and synthetic alcohols (which can be branched or linear) and prepared from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, ethoxylated alkanolamides and alkanolamides; alkoxylated triglycerides,
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22/81 such as ethoxylated soy beans, castor oils and rapeseed; alkylphenol alkoxylates, such as octyl phenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers in which the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; fatty esters and ethoxylated oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin based derivatives, polyethoxylated esters, such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives, such as sorbitan esters; Polymeric surfactants, such as random copolymers, block copolymers, peg resin (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar derivatives, such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.
[074] Useful anionic surfactants include, but are not limited to: alkyl aryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives, such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters, such as alkoxylated alcohol phosphate esters, alkylphenol alkoxylate phosphate esters and styryl phenol ethoxylated phosphate esters; protein-based surfactants; sarcosine derivatives; styryl phenolic ether sulfate; sulfates and sulfonates from oils and fatty acids; ethoxylated alkyl phenols sulfates and sulfonates;
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23/81 alcohol sulfates; ethoxylated alcohol sulfates; sulfonates of amines and amides, such as M, M-alkyltaurates; benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes sulfonates; condensed naphthalene sulfonates; naphthalene and alkyl naphthalene sulfonates; fractionated petroleum sulfonates; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkyl sulfosuccinate salts.
[075] Useful cationic surfactants include, but are not limited to: ethoxylated amides and amides; amines such as M-alkyl propanodiamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared 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- (2hydroxyethyl) -alkylamine oxides.
[076] Mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants are also useful for the present compositions. Nonionic, anionic and cationic surfactants and their recommended uses are featured in a variety of published references, including McCutcheonS Emulsifiers and Detergents, 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, USA, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, seventh edition, John Wiley and Sons, New York, USA, 1987.
[077] The compositions of this invention may also contain formulation aids and additives, known to those skilled in the art as formulation aids (some of which can be
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24/81 considered to also function as solid thinners, liquid thinners or surfactants). Such formulation aids and additives can control: pH (buffers), defoaming during processing (defoamers, such as polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), microbial growth in containers (microbicides), freezing product (anti-freeze), color (dyes / pigment dispersions), dissolution removal (film or adhesive formers), evaporation (evaporation retardants), and other formulation attributes. Film-forming agents include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation aids and additives include those listed in McCutcheonS Volume 2: Functional Materials, American and International editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co .; and PCT publication WO 03/024222.
[078] The Formula 1 compound and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or grinding it in a dry liquid or diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is immiscible with water, an emulsifier is typically added to emulsify the solvent it contains active by diluting it with water. Active ingredient slurries with particle diameters up to 2,000 pm can be wet milled using medium mills to obtain particles with average diameters below 3 pm. The aqueous slurries can be transformed into finished suspension concentrates (see, for example, US 3,060,084) or further processed by drying by
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25/81 atomization to form water-dispersible granules. Dry formulations require dry milling processes, which produce average particle diameters in the range of 2 to 10 pm. Dusts and powders can be prepared by mixing and normally crushing (as with a hammer mill or fluid energy mill). Granules and pellets can be prepared by spraying the active material using preformed granular vehicles or by agglomeration techniques. See Browning, Agglomeration, Chemical Engineering, December 4, 1967, pages 147 to 48, PerryS Chemical EngineerS Handbook, 4th Ed., McGraw-Hill, New York, USA, 1963, pages 8 to 57 and following, and WO 91 / 13546. Pellets can be prepared as described in US 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in US 4,144,050, US 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in US 5,180,587, US 5,232,701 and US 5,208,030. Films can be prepared as taught in GB 2,095,558 and US 3,299,566.
[079] For additional information regarding the formulation technique, see TS Woods, The Formulatods Toolbox - Product Forms for Modern Agriculture in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and TR Roberts, Eds., Works 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pages 120 to 133. See also US 3,235,361, column 6, line 16 to column 7, line 19 and examples 10 to 41; US 3,309,192, column 5, row 43 to column 7, row 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138 to 140, 162 to 164, 166, 167 and 169 to 182; US 2,891,855, column 3, row 66 through column 5, row 17 and examples 1 to 4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, USA, 1961, pages 81 to 96; Hance et al., Weed Control Handbook, 8th Edition, Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, United Kingdom, 2000.
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26/81 [080] In the following examples, all formulations are prepared in conventional ways. Without further elaboration, it is believed that an individual skilled in the technique using the above description can use the present invention to its fullest extent. The following examples should, therefore, be interpreted as merely illustrative, and not limiting the disclosure in any way. The percentages are by weight, unless otherwise indicated.
Example A
High Strength Concentrate
Compound 1 98.5% silica airgel 0.5% synthetic amorphous fine silica 1.0%
Example B
Wetting powder
Compound 1 65.0% polyethylene dodecylphenol glycether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%
Example C granule
Compound 1 10.0% atapulgite granules (low volatility matter, 0.71 / 0.30mm; USS screens. n ° 25 to 50 90.0%
Example D
Extruded pellet
Compound 1 25.0% anhydrous sodium sulfate 10.0% raw calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium / magnesium bentonite 59.0%
Example E
Emulsifiable concentrate
Compound 1 10.0% polyoxy ethylene sorbitol hexoleate 20.0% C6-C10 fatty acid methyl ester 70.0%
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Example F
MICROEMULSION
Compound 1 5.0% polyvinylpyrrolidone-vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% Water 20.0%
Example G
Seed treatment
Compound 1 20.00% polyvinylpyrrolidone-vinyl acetate copolymer 5.00% lignite acid wax 5.00% calcium ligninsulfonate 1.00% polyoxy / polyoxypropylene ethylene block copolymers 1.00% stearyl alcohol (POE 20) 2.00% polyorganosilane 0.20% red pigment dye 0.05% Water 65.75%
Example H
Fertilizer stick
Compound 1 2.50% pyrrolidone-styrene copolymer 4.80% 16-tristyrylphenyl ethoxylate 2.30% baby powder 0.80% maize starch 5.00% slow release fertilizer 36.00% kaolin 38.00% Water 10.60%
Example I
Suspension concentrate
Compound 1 35% butyl polyoxyethylene / polypropylene block copolymer 4.0% stearic acid / polyethylene copolymer 1.0% acrylic styrene polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1% 1,2-benzisothiazolin-3-one 0.1% Water 53.7%
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Example J
Emulsion in water
Compound 1 10.0% butyl polyoxyethylene / polypropylene block copolymer 4.0% stearic acid / polyethylene copolymer 1.0% acrylic styrene polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1% 1,2-benzisothiazolin-3-one 0.1% aromatic petroleum-based hydrocarbon 20.0 Water 58.7%
Example K
Oil dispersion
Compound 1 25% polyoxyethylene sorbitol hexaoleate 15% organically modified bentonite clay 2.5% fatty acid methyl ester 57.5%
Example L
Suspoemulsion
Compound 1 10.0% fipronil (second active ingredient) 5.0% butyl polyoxyethylene / polypropylene block copolymer 4.0% stearic acid / polyethylene copolymer 1.0% acrylic styrene polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1% 1,2-benzisothiazolin-3-one 0.1% aromatic petroleum-based hydrocarbon 20.0% Water 53.7%
[081] The compounds of this invention exhibit activity against a wide spectrum of invertebrate pests. These pests include invertebrates that inhabit a variety of environments, such as plant foliage, roots, soil, harvested crops or other foods, building structures or animal integuments. Such pests include, for example, invertebrates that feed on foliage (including leaves, stems, flowers and fruits), seeds, wood, textile fibers or blood or animal tissues, and thereby cause injury or damage to, for example, example, agronomic crops
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29/81 cultivated or stored, forests, greenhouse crops, ornamentals, nursery crops, stored food or fiber products, or houses and other structures and their contents, or may be harmful to animal health or public health. Those skilled in the art will find that not all compounds are equally effective against all growth stages of all pests.
[082] These compounds and compositions present are then agronomically useful to protect field crops from phytophagous invertebrate pests, and also nanoagronomically to protect other horticultural crops and plants from phytophagous invertebrate pests. This utility includes protecting crops and other plants (that is, both agronomic and non-agronomic) that contain genetic material introduced by genetic engineering (ie, transgenic) or modified by mutagenesis to provide advantageous traits. Examples of such traits include tolerance to herbicides, resistance to phytophagous pests (eg insects, mites, aphids, spiders, nematodes, snails, pathogenic plant fungi, bacteria and viruses), improved plant growth, increased tolerance to adverse growth, such as high or low temperatures, high or low humidity, and high salinity, increased flowering or fruit production, higher crop yields, more rapid ripening, superior quality and / or nutritional value of the harvested product, or storage properties or improved process of harvested products. Transgenic plants can be modified to express multiple traits. Examples of plants that contain traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybeans and potatoes that express an insecticidal toxin from Bacillus thuringiensis, such as YIELD GARD®, KNOCKOUT®, STARLINK®, BOLLGARD®, NuCOTN® and NEWLEAF ®, and herbicide-tolerant varieties of corn, cotton, soybeans and rapeseed, such as ROUNDUP READY®,
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LIBERTY LINK®, IMI®, STS® and CLEARFIELD®, as well as cultures that express M-acetyltransferase (GAT) to provide resistance to glyphosphate herbicide, or cultures that contain the HRA gene that provides resistance to herbicides that inhibit acetolactate synthase (ALS ). The present compounds and compositions can interact synergistically with traits introduced by genetic engineering or modified by mutagenesis, thereby enhancing the phenotypic expression or effectiveness of the traits or increasing the invertebrate pest control effectiveness of the present compounds and compositions. In particular, the present compounds and compositions can interact synergistically with the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide greater than additive control of these pests.
[083] The compositions of this invention may also optionally comprise plant nutrients, for example, a fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron , manganese, zinc, and molybdenum. Of importance are compositions that comprise at least one fertilizer composition that comprises at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnesium. Compositions of the present invention that additionally comprise at least one plant nutrient can be in the form of liquids or solids. Solid formulations in the form of granules, small sticks or tablets are of importance. Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with the fertilizer composition with other formulation ingredients and then preparing the formulation by methods such as granulation or extrusion. Alternatively, solid formulations can be prepared by spraying
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31/81 of a solution or suspension of a compound or composition of the present invention in a volatile solvent in a fertilizer composition previously prepared in the form of dimensionally stable mixtures, for example, granules, small sticks or tablets, and then by evaporation of the solvent.
Agronomic and non-agronomic pests [084] Examples of agronomic or non-agronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as cartridge caterpillars, borers, false pans, and heliothines in the Noctuidae family (for example, pink stem borer ( Sesamia injerens Walker), corn stem borer (Sesamia nonagrioides Lefebvre), southern cartridge caterpillar (Spodoptera eridania Cramer), autumn cartridge caterpillar (Spodoptera fugiperda JE Smith), beet cartridge caterpillar (Spodoptera exigua Hiibner), cotton leaf caterpillar (Spodoptera littoralis Boisduval), yellow-striped cartridge caterpillar (Spodoptera ornithogalli Guenee), black borers (Agrotis ipsilon Hufnagel), soybean caterpillar (Anticarsia gemmatalis Hiibner), green fruit caterpillar (Lith) cabbage cartridge caterpillar (Barathra brassicae Linnaeus), false soy bean medium (Pseudoplusia includens Walker), false cabbage medium (Tri choplusia ni Hiibner), tobacco caterpillar (Heliothis virescens Fabricius)); borcas, moths, hairy caterpillars, coneworm caterpillars, cabbage caterpillars and leaf mining caterpillars of the Pyralidae family (for example, European corn borer (Ostrinia nubilalis Hiibner), citrus mining larva (Amyelois transitella Walker), pinworm root larva corn (Crambus caliginosellus Clemens), lawn caterpillar (Pyralidae: Crambinae) as lawn caterpillar (Herpetogramma licarsisalis Walker), sugar cane stem borer (Chilo infuscatellus Snellen), small tomato borer (Neoleucinodes elegantalis Guenee), green winding caterpillar (Cnaphalocerus medinalis), mining caterpillar
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32/81 of fruit trees (Desmia funeralis Hiibner), melon caterpillar (Diaphania nitidalis Stoll), cabbage center larva (Helluala hydralis Guenee), yellow stem borer (Scirpophaga incertulas Walker), seedling borer (Scirpophaga infuscatellus Snellen), white stem borer (Scirpophaga innotata Walker), top seedling borer (Scirpophaga nivella Fabricius), dark-headed rice borer (Chilo polichrysus Meyrick), cabbage brindle caterpillar (Crocidolomia binotalis English)); winding caterpillars, bud caterpillars, seed caterpillars, and fruit caterpillars in the Tortricidae family (for example, apple moth (Cydia pomonella Linnaeus), grape moth (Endopiza viteana Clemens), oriental fruit moth (Grapholita molesta Busck), false citrus apple moth (Cryptophlebia leucotreta Meyrick), citrus borer (Ecdytolopha aurantiana Lima), red band winder (Argyrotaenia velutinana Walker), apple winder (Choristoneura rosaceana Harris), light brown apple moth (Epiphyas postvana) , European grape moth (Eupoecilia ambiguella Hiibner), apple bud moth (Pandemis pyrusana Kearfott), omnivorous winder (Platynota stultana Walsingham), fruit tree tortricide (Pandemis cerasana Hiibner), brown apple tortricide (Pandemis heparana Denis Schiffermuller)); and many other lepidoptera of economic importance (for example, cruciferous moth (Plutella xylostella Linnaeus), pink caterpillar (Pectinophora gossypiella Saunders), cork oak caterpillar (Lymantria dispar Linnaeus), peach borer (Carposina niponensis Walsingham), peach (Anarsia lineatella Zeller), potato caterpillar (Phthorimaea operculella Zeller), marble mining caterpillar (Lithocolletis blancardella Fabricius), Asian fruit leaf mining caterpillar (Lithocolletis ringoniella Matsumura), rice leaf caterpillar (Lerodea eufala) mining of fruit leaves (Leucoptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea, including cockroaches from the Blattellidae families
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33/81 and Blattidae (for example, oriental cockroach (Blatta orientalis Linnaeus), Asian cockroach (Blatella asahinai Mizukubo), German cockroach (Blattella germanica Linnaeus), water cockroach (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus) , brown cockroach (Periplaneta brunnea Burmeister), wood cockroach (Leucophaea maderae Fabricius)), soot brown cockroach (Periplaneta fuliginosa Service), Australian cockroach (Periplaneta australasiae Fabr.), waterfall cockroach (Nauphoeta cinerea Olivier) and wild cockroach (Symploce Stephens pattens)); eggs, adults and leaf feeding larvae, fruit feeding, root feeding, seed feeding and vesicular tissue feeding of the order Coleoptera, including weevils from the families Anthribidae, Bruchidae, and Curculionidae (for example, cotton weevil (Anthonomus grandis Boheman ), water weevil (Lissorhoptrus oryzophilus Kuschel), cereal weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oryzae Linnaeus)), annual lawn weevil (Listronotus maculicollis Dietz), blue grass weevil (Sphenophorus) hunter (Sphenophorus venatus vestitus), Denver weevil (Sphenophorus cicatristriatus Fahraeus)); jumping beetles, cucumber beetles, chrysomelids, leaf beetles, potato beetles, and mining caterpillars in the Chrysomelidae family (for example, Colorado potato beetle (Leptinotarsa decemlineata Say), western corn chrysomelid (Diabrotica virgifera virgifera LeConte)); beetle and other beetles of the Scarabaeidae family (for example, Japanese beetle (Popillia japonica Newman), oriental beetle (Anomala orientalis waterhouse, Exomala orientalis (waterhouse) Baraud), northern masked beetle (Cyclocephala borealis Arrow), southern masked beetle (Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and john crackling (Aphodius spp.), black grass ataenius (Ataenius spretulus Haldeman), green June beetle (Cotinis nitida Linnaeus), Asian garden beetle (Maladera castanea
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Arrow), May / June beetles (Phyllophaga spp.) And European beetle (Rhizotrogus majalis Razoumowsky)); carpet beetles in the family Dermestidae; wire larvae of the Elateridae family; live woodworm from the family Scolytidae and flour beetles from the family Tenebrionidae. In addition, agronomic and non-agronomic pests include: eggs, adults and larvae of the order of Dermaptera, including lacruses of the family Forficulidae (for example, European lacraia (Forficula auricularia Linnaeus), black lacraia (Chelisoches morio Fabricius)); eggs, immature, adults and nymphs of the orders Hemiptera and Homoptera as plant insects of the Miridae family, cicadas of the Cicadidae family, grasshoppers (for example Empoasca spp.) of the Cicadellidae family, moths (for example, Cimex lectularius Linnaeus) of the Cimicidae family, fulgoromorphs of the families Fulgoroidae and Delphacidae, members of the family Membracidae, psyllids of the family Psyllidae, aleirodids of the family Aleyrodidae, aphids of the family Aphididae, phylloxera of the family Phylloxeridae, floury insects of the family Pseudococcidae, insects of the Tingidae family, Pentatomidae of the Pentatomidae family, grass bug (for example, hairy grass bug (Blissus leucopterus hirtus Montandon) and southern grass bug (Blissus insularis Barber)) and other seed insects of the Lygaeidae family , leafhoppers of the family Cercopidae, pests of pumpkin from the family Coreidae, and red insects and cotton stains from the family Pyrrhocoridae. Also included are eggs, larvae, nymphs and adults of the order Acari (mites), such as spider mites and red mites of the family Tetranychidae (for example, European red mite (Panonychus ulmi Koch), two-spot mite (Tetranychus urticae Koch), McDaniel mite (Tetranychus mcdanieli McGregor)); flat mites of the family Tenuipalpidae (for example, citrus flat mites (Brevipalpus lewisi McGregor)); bud and false mites
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35/81 rust of the Eriophyidae family and other foliar feeding mites and mites important for human and animal health, that is, dust mites of the Epidermoptidae family, follicle mites of the Demodicidae family, grain mites of the Glycyphagidae family; ticks of the Ixodidae family, commonly known as ticks (for example, deer tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes holocyclus Neumann), American dog tick (Dermacentor variabilis Say), lone star tick (Amblyomma americanum Linnaeus) ) and ticks of the Argasidae family, commonly known as soft ticks (for example, recurrent fever tick (Ornithodoros turicata), common chicken tick (Argas radiatus)); eschar and itch mites from the Psoroptidae, Pyemotidae, and Sarcoptidae families; eggs, adults and immatures of the order Orthoptera, including locusts, locust beans and crickets (eg migratory locusts (eg Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American locusts (eg Schistocerca americana Drury), desert locust ( Schistocerca gregaria Forskal), migratory locust bean (Locusta migratoria Linnaeus), bush locust bean (Zonocerus spp.), Domestic cricket (Acheta domesticus Linnaeus), mole crickets (eg brownish mole cricket (Scapteriscus vicinus Scuddereira) and cricket (Scapteriscus borellii Giglio-Tos)); eggs, adults and immature of the order Diptera, including miners (for example, Liriomyza spp. as a leaf miner (Liriomyza sativae Blanchard)), mosquitoes, fruit flies (Tephritidae) , wheat flies (for example, Oscinella frit Linnaeus), soil worms, house flies (for example, Musca domestica Linnaeus), small house flies (for example, Fanni a Canicularis Linnaeus, F. femoralis Stein), stable flies (for example, Stomoxys calcitrans Linnaeus), face flies, horn flies, blowflies (for example, Chrysomya spp., Phormia spp.), and other fly pests muscoids,
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36/81 horseflies (for example, Tabanus spp.), Berne (for example, Gastrophilus spp., Oestrus spp.), Cattle larvae (for example, Hypoderma spp.), Deer flies (for example, Chrysops spp.) , ked flies (for example, Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (for example, Aedes spp., Anopheles spp., Culex spp.), black flies (for example, Prosimulium spp., Simulium spp.), biting flies, sand flies, sciarid flies, and other Nematocera; eggs, adults and immatures of the order Thysanoptera, including onion thrips (Thrips tabaci Lindeman), flower thrips (Frankliniella spp.), and other leaf feeding thrips; insect pests of the order Hymenoptera, including ants of the Formicidae family, including the Florida carpenter ant (Camponotus floridanus Buckley), red carpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant (Camponotus pennsylvanicus De Geer), white paw ant (Technomyr albipes fr. Smith), loggerhead ants (Pheidole sp.), phantom ants (Tapinoma melanocephalum Fabricius); pharaoh ant (Monomorium pharaonis Linnaeus), red-hot ant (Wasmannia auropunctata Roger), fire ant (Solenopsis geminata Fabricius), imported red fire ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), crazy ant (Paratrechina Latreille), asphalt ant (Tetramorium caespitum Linnaeus), cornfield ant (Lasius alienus Forster) and odorous domestic ant (Tapinoma sessile Say). Other Hymenoptera, including bees (including carpenter bees), hornets, yellow-jacketed wasps, wasps, and crabro wasps (Neodiprion spp .; Cephus spp.); insect pests of the order Isoptera, including termites of the Termitidae (eg, Macrotermes sp., Odontotermes obesus Rambur families), Kalotermitidae (eg, Cryptotermes sp.), and Rhinotermitidae (eg Reticulitermes sp., Coptotermes sp., Heterotermes tenuis Hagen), the subterranean termite from the east 8Retululitermes flavipes Kollar), subterranean termite from the west
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37/81 (Reticulitermes hesperus Banks), underground Formosa termite (Coptotermes formosanus Shiraki), West Indian dry wood termite (Incisitermes immigrans Snyder), powder powders (Cryptotermes brevis Walker), dry wood termite (Incisitermes snyderi Light ), subterranean termite from the southeast (Reticulitermes virginicus Banks), termite from dry wood from the west (Incisitermes minor Hagen), arboreal termites, such as Nasutitermes sp. and other termites of economic importance; insect pests of the order Thysanura, such as the silverfish (Lepisma saccharina Linnaeus) and firebrat moths (Thermobia domestica Packard); insect pests of the order Mallophaga and including loot (Pediculus humanus capitis De Geer), pediculid (Pediculus humanus Linnaeus), chicken louse (Menacanthus stramineus Nitszch), dog louse (Trichodectes canis De Geer), feather louse (Goniocotes gallinae De Geer), sheep louse (Bovicola ovis Schrank), sucking louse (Haematopinus eurysternus Nitzsch), chewing louse (Linognathus vituli Linnaeus) and other sucking and chewing lice that attack humans and animals; insect pests of the order Siphonoptera, including the eastern rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephalides canis Curtis), chicken flea (Ceratophyllus gallinae Schrank), bird flea ( Echidnophaga gallinacea Westwood), human fleas (Pulex irritans Linnaeus) and other fleas that afflict mammals and birds. Additional arthropod pests that are affected include: spiders of the order Araneae, such as the brown spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow (Latrodectus mactans Fabricius), and centipedes of the order Scutigeromorpha like the domestic centipede (Scutigera coleoptrata Linnaeusus). Compounds of the present invention also have activity in members of the Nematoda, Cestoda, Trematoda, and Acanthocephala Classes, including members of economic importance from the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida,
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38/81 and Enoplida, as, but without limitation, pests of agricultural importance, (ie nematodes of the root nodules of the genus Meloidogyne, lesion nematodes of the genus Pratylenchus, nematode of the root atrophy in the genus Trichodorus, etc.) and pests to animal and human health (ie all trematodes, tapeworms and ascarids of economic importance, such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in dogs, Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus ruminants, etc.).
[085] Compound 1 of the invention shows a particularly high activity against pests in the order Lepidoptera (eg Alabama argillacea Hiibner (cotton leaf caterpillar), Archips argyrospila Walker (fruit tree reels), A. rosana Linnaeus (European winder ) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenee (rice winder), Crambus caliginosellus Clemens (hairy corn rootworm), Crambus teterrellus Zincken (hairy blue grass caterpillar), Cydia pomnaella Linnaeus (apple moth), Earias insulana Boisduval (Egyptian caterpillar), Earias vittella Fabricius (pink caterpillar), Helicoverpa armigera Hiibner (American caterpillar), Helicoverpa zea Boddie (corn cob caterpillar), Heliothis virescens Fabricius (gaterpillar caterpillar) tobacco), Herpetogramma licarsisalis Walker (lawn caterpillar), Lobesia botrana Denis & Schiffermiiller (grape fruit moth), Pectino phora gossypiella Saunders (pink caterpillar), Phyllocnistis citrella Stainton (citrus mining caterpillar), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (cruciferous moth), Spodoptera exigua Hiib of the beet cartridge), Spodoptera litura Fabricius (military tobacco caterpillar, burst caterpillar), Spodoptera frugiperda JE Smith (autumn cartridge caterpillar), Trichoplusia ni Hiibner (false
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39/81 cabbage) and Tuta absoluta Meyrick (tomato caterpillar from Minas Gerais)).
[086] Compound 1 of the invention also has activity in members of the order Homoptera, including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (black bean aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (phyllid aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov / Mordvilko (Russian wheat aphid), Dysaphis plantaginea Paaserini (pink apple aphid), Eriosoma lanigerum Hausmann (apple aphid aphid), Hyalopterus pruni Geoffroy (flour aphid), Lipaphis erysimi Kaltenium rhodium, aphrodisiacal, aphrodisiacal (cereal aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid, green peach aphid), Nasonovia ribisnigri Mosley (af dio lettuce), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (cornfield leaf aphid), Rhopalosiphum padi Linnaeus (oat aphid), Schizaphis graminum Rondani (green aphid from cereals), Sitobion avenae Fabricius (English aphid), Therio Buckton maculata (spotted afalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxera devastatrix Pergande (pecan phylloxera); Bemisia tabaci Gennadius (tobacco whitefly, sweet potato whitefly), Bemisia argentifolii Bellows & Perring (silver leaf whitefly), Dialeurodes citri Ashmead (citrus whitefly) and Westwood Trialeurodes vaporariorum (greenhouse whitefly); Empoasca fabae Harris (potato grasshopper), Laodelphax striatellus Fallen (minor brown glow), Macrolestes quadrilineatus Forbes (aster grasshopper), Nephotettix cinticeps Uhler (green grasshopper), Nephotettix nigropictus Stal (Grasshopper of stal
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40/81 rice), Nilaparvata lugens Stal (brown glow), Peregrinus maidis Ashmead (corn glow), Sogatella furcifera Horvath (white back glow), Sogatodes orizicola Muir (rice delfacid), white apple gyroscope ), Ery throne oura spp. (grape grasshoppers); Magicidada septendecim Linnaeus (periodic cicada); Icerya purchasi Maskell (Australian scale), Quadraspidiotus perniciosus Comstock (San Jose scale); Planococcus citri Risso (floury citrus mealybug); Pseudococcus spp. (another floury mealybug complex); Cacopsylla pyricola Foerster (pear psylla), Trioza diospyri Ashmead (pear psyllid).
[087] Compound 1 of this invention also has activity in members of the order Hemiptera, including: Acrosternum hilare Say (green pentatomid), Anasa tristis De Geer (pumpkin insect), Blissus leucopterus leucopterus Say (grass bug), Cimex lectularius Linnaeus (bug) Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich-Schaffer (cotton stain), Euchistus servus Say (marbled pentatomid), Euchistus variolarius Palisot de Beauvois one spot), Graptosthetus spp. (buggy complex), Leptoglossus corculus Say (leaf seed insect), Lygus lineolaris Palisot de Beauvois (spotted plant bug), Nezara viridula Linnaeus (southern green pentatomid), Oebalus pugnax Fabricius (rice pentatomid), Oncopeltus fast Dallas (stink bug), Pseudatomoscelis seriatus Reuter (cotton salton flea). Other insect orders controlled by compounds of the invention include Thysanoptera (for example, Frankliniella occidentalis Pergande (thrips of the western flower), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (thrips) onion); and
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41/81 order Coleoptera (for example, Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and wire worms of the genus Agriotes, Athous or Limonius).
[088] Note that some contemporary classification systems place Homoptera as a suborder of the order Hemiptera.
[089] It is important to use compound 1 of this invention to control silver leaf whiteflies (Bemisia argentifolii). It is important to use compound 1 of this invention to control western flower tripe (Frankliniella occidentalis). It is of importance to use compound 1 of this invention to control potato locust (Empoasca fabae). It is important to use compound 1 of this invention to control the cruciferous moth (Plutella xylostella). It is important to use the compound 1 of this invention to control the autumn cartridge caterpillar (Spodoptera frugiperda).
Agronomic Compositions / Mixtures [090] Compounds of this invention can also be mixed with one or more biologically active compounds or agents, including insecticides, fungicides, nematocides, bactericides, acaricides, herbicides, herbicide protectors, growth regulators, as insect seedling inhibitors and rooting stimulants, chemosterilants, semi-chemicals, repellents, attractants, pheromones, food stimulants, other biologically active compounds or entomopathogenic bacteria, viruses or fungi to form a multi-component pesticide, which yields an even broader spectrum of agronomic and non-useful utility agronomic. Therefore, the present invention also relates to a composition which comprises a biologically effective amount of a Formula 1 compound and an effective amount of at least one additional biologically active compound or agent and may further comprise at least one among surfactants,
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42/81 thinners solid or liquid thinners. For mixtures of the present invention, the other biologically active compounds or agents can be formulated together with the present compounds, including the compound of Formula 1, to form a premix, or the other biologically active compounds or agents can be formulated separately from of the present compounds, including the compound of Formula 1, and the two formulations combined before application (for example, in a spray tank) or, alternatively, applied in succession.
[091] Compound 1 of this invention can also be mixed with one or more of the other biologically active compounds or agents including insecticides, fungicides, nematocides, bactericides, acaricides, herbicides, herbicide protectors, growth regulators, as insect and root stimulants, chemosterilizers, semi-chemicals, repellents, attractants, pheromones, food stimulants, other biologically active compounds or bacteria, viruses or entomopathogenic fungi, to form a multi-component pesticide that yields an even broader spectrum of agronomic and non-agronomic. Accordingly, the present invention also relates to a composition that comprises a biologically effective amount of a Formula 1 compound, at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, and at least one compound or additional biologically active agent. For mixtures of the present invention, the other biologically active compounds or agents can be formulated together with the present compounds, including the compound of Formula 1, to form a premix, or the other biologically active compounds or agents can be formulated separately from of the present compounds, including the Formula 1 compound, and the two formulations combined prior to application (for example,
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43/81 in a sprinkler tank) or, alternatively, applied in succession.
[092] Examples of such biologically active compounds or agents with which the compounds of this invention can be formulated are insecticides, such as abamectins, acephate, acequinocyl, acetamipride, acrinatrine, amidoflumet, amitraz, avermectin, azadiractin, azinfosmethyl, bifentazine, biphenazate , bistriflurone, borate, 3-bromo-1- (3-chloro-2-pyridinyl) -M- [4-cyano-2methyl-6 - [(methylamino) carbonyl] phenyl] -1H-pyrazol-5-carboxamide, buprofezine , cadusafos, carbarila, carbofuran, cartap, carzol, chlorantraniliprol, chlorfenapyr, chlorfluazurone, chlorpyrifos, chlorpyrifos-methyl, chromafenozida, clofentezina, chothlidine, cyflothmethrin, cytothyrethine, gamma-cytothyrethine, cytothyrethine, beta-cytothruthine , zetacipermethrin, cyromazine, deltamethrin, diafentiurone, diazinone, dieldrin, diflubenzurone, dimeflutrin, dimehipo, dimetoate, dinotefuran, diofenolane, emamectin, endosulfan, sphenolerate, etiprole, ethoxide, ethoxide, ethoxide, ethoxide, ethoxide, ethoxide, ethoxide, ethoxide, ethoxine, ethoxide, ethoxide, a, phenothiocarb, phenoxycarb, fenpropatrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucithrinate, flufenerin, flufenoxurone, fluvalinate, tau-fluvalinate, fonofos, formetanate, fostiazate, halofenoxidone, hexofloxide, hexofloxide, hexofloxide , lufenurone, malationa, metaflumizone, metaldehyde, metamidophos, methidathione, metiodicarb, methomyl, methoxy, methoxychlor, methoxyfenozide, metoflutrin, milbemycin oxime, monocrotofos, nicotine, nitenpiram, nitiazine, parnururin, parnururone, novalurone, novalurone, novalurona, phorate, fosalone, fosmet, fosfamidone, pirimicarb, profenofos, proflutrina, propargita, protrifenbuto, pimetrozina, pirafluprol, pyrethrin, pyridabene, pyridalil, pyrifluquinazone, pyriprol, pyriproxifene, rotenone, spyronine, spironodine, spironodine, spironodine tebufenozide, tebufenpirad, teflubenzurone, teflutrin, terbufos, tetrachlorvinfo s, tetramethrin, tiacloprid, tiametoxam, tiodicarb, tiosultap-sodium, tolfenpirad,
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44/81 tralometrine, triazamate, trichlorfone, triflumurone, Bacillus thuringiensis delta-endotoxins, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.
[093] Insecticides such as abamectin, acetamipride, acrinatrine, amitraz, avermectin, azadiractin, bifenthrin, 3bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2-methyl-6- [ (methylamino) carbonyl] phenyl] -1Hpyrazol-5-carboxamide, buprofezin, cadusaphos, carbaryl, cartap, chloranthranilprol, chlorphenyl, chlorpyrifos, clothianidin, cyfluthrin, beta-cyflothrin, cyhalothrin, gamma-cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, cyhalothrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolane, emamectin, endosulfan, sphenolvalate, etiprol, etofenprox, ethoxyazide, floxamide, floxamide, floxamide, floxamide, flonicamid, flonicamid, flonicamid, flonicamidone imidacloprid, indoxacarb, lufenurone, metaflumizone, metiodicarb, metomil, methoprene, methoxyfenozide, nitenpiram, nitiazine, novalurone, oxamila, pymetrozine, pyrethrin, pyridabene, pyridalyl, pyriproxifene, ryanodine, spyanamine, ryanodine, spyanamine pinsad, spirodiclofen, spiromesifene, spirotetramat, tebufenozide, tetramethrin, thiaclopride, thiametoxam, tiodicarb, thiosultap-sodium, tralometrine, triazamate, triflumuron, delta-endotoxins of Bacillus thuringiensis, all the strains of Bacillus thuringiensis all the strains of Bacillus thuringiis and all the strains of Bacillus thuringiensis.
[094] One embodiment of biological agents for mixing with compounds of this invention include entomapathogenic bacteria, such as Bacillus thuringiensis, and the encapsulated delta-endotoxins of Bacillus thuringiensis (for example, Cellcap, MPV, MPVII); entomapathogenic fungi, such as the green muscardine fungus; and entomapatogenic viruses (both naturally occurring and genetically modified), including baculovirus, nucleopolyhedron virus (NPV), such as Helicoverpa zea nucleopolihedrovirus
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45/81 (HzNPV), Anagrafa falcifera nucleopolihedrovirus (AfNPV); and granulose virus (GV), such as Cydia pomonella granulosis virus (CpGV).
[095] Of particular interest is a combination in which the other active invertebrate pest control ingredient belongs to a different chemical class or has a different site of action than the Formula 1 compound. In certain cases, a combination with at least one other invertebrate pest control active ingredient that has a similar spectrum of control, but a different site of action will be particularly advantageous for resistance management. Therefore, a composition of the present invention may further comprise a biologically effective amount of at least one additional invertebrate pest control active ingredient that has a similar spectrum of control, but which belongs to a different chemical class or has a site different action. Such additional biologically active compounds or agents include, but are not limited to, sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimeflutrin, sphenolvalate, fenvalerate, indoxacina, proflutrina, pyrethrin and tralometrine; cholinesterase inhibitors, such as chlorpyrifos, metomyl, oxamil, tiodicarb and triazamate; neonicotinoids, such as acetamipride, clothianidin, dinotefuran, imidacloprid, nitenpiram, nitiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones, such as espinetoram, spinosad, abamectin, avermectin and emamectin; GABA chlorine channel antagonists (γaminobutyric acid) -dependent, such as avermectin or blockers, such as ethiprole and fipronil; chitin synthesis inhibitors, such as buprofezin, cyromazine, fluphenoxurone, hexaflumurone, lufenurone, novalurone, noviflumurone and triflumurone; juvenile hormone simulators, such as diophenolane, phenoxycarb, methoprene and pyriproxyphene; octopamine receptor ligands, such as amitraz; molting inhibitors and ecdysone agonists, such as azadiractin,
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46/81 methoxyfenozide and tebufenozide; ryanodine receptor ligands, such as rianodine, anthranilic diamides, such as chlorantraniliprol (see US patent 6,747,047, PCT publications WO 2003/015518 and WO 2004/067528) and flubendiamide (see US patent 6,603,044); nereistoxin analogues, such as cartap; mitochondrial electron transport inhibitors, such as chlorfenapyr, hydramethylnone and pyridabene; lipid biosynthesis inhibitors, such as spirodiclofen and spiromesifene; cyclodiene insecticides, such as dieldrin or endosulfan; pyrethroids; carbamates; insecticidal ureas; and biological agents, including nucleopolyhedron virus (NPV), members of Bacillus thuringiensis, encapsulated Bacillus thuringiensis delta-endotoxins, and other naturally occurring or genetically modified insecticidal viruses.
[096] Additional examples of biologically active compounds or agents with which the compounds of this invention can be formulated are: fungicides, such as acibenzolar, aldimorph, ametoctradine, amisulbrom, azaconazole, azoxystrobin, benalaxyl, benomile, bentiavalicarb, bentiavalicarb-isopropyl, binocular, binocular biphenyl, bitertanol, blasticidin-S, Bordeaux mixture (tribasic copper sulphate), boscalide / nicobifene, bromuconazole, bupirimate, butiobate, carboxine, carpropamide, captafol, captan, carbendazim, chloroneb, chlorotalonyl, clozolinate, clozolinate, clozolinate copper salts such as copper sulfate and copper hydroxide, cyzofamide, cyflunamide, cymoxanil, cyproconazole, cyprodinil, diclofluanide, diclocimet, diclomezine, dichlorane, dietofencarb, diphenoconazole, dimetomorf, dimoxystrobin, diniconazol, diniconazol, diniconazol, diniconazol, diniconazol, diniconazol dodemorfo, dodina, econazole, etaconazole, edifenfos, epoxiconazole, ethaboxam, etirimol, etridiazole, famoxadone, fenamid ona, fenarimol, fenbuconazole, fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidina, fenpropimorfo, fentina acetate, fentina hydroxide, ferbam, ferfurazoate, ferimzone, fluazinam, fluudioxon, fluoro, flumetover, flumetover
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47/81 fluquinconazole, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetil-aluminum, fuberidazole, furalaxila, furametapyr, hexaconazole, himexazole, guazatin, imazalila, imibenconazole, iodocprazole, iinoctazol, iinoctazone, , isoprothiolan, casugamycin, cresoxim-methyl, mancozeb, mandipropamide, maneb, mapanipyrine, mefenoxam, mepronyl, metalaxyl, metconazole, metasulfocarb, metometostrobin / phenominostrobin, mepanipyrim, metrafenone, miconazoline, miconazoline, miconazolate, miconazoline, , octilinone, ofuraca, orisastrobina, oxadixila, oxolinic acid, oxpoconazole, oxycarboxine, paclobutrazol, penconazole, pencicuron, penflufen, pentiopirad, perfurazoate, phosphonic acid, phthalide, picobenzamide, picoxystrobam, propoxybol, propoxazole, propoxybol, procoxazamine, propoxazole , propiconazole, propineb, proquinazid, protioconazole, pyraclostrobin, pirametostrobin, p iraoxystrobin, pyrazophos, pyrifenox, pyrimethanil, pyrifenox, pyrolnitrine, pyroquilone, quinconazole, quinoxifene, quintozene, siltiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquine, tebufozoan, tezufan, tetanazone, tetanazol, tetanazol, tetanazol, tetanazone methyl, tiram, thiadinil, tolclofos-methyl, tolifluanide, triadimefone, triadimenol, triarimol, triazoxide, tridemorf, tricyclazole trimoprhamide, trifloxystrobin, triforine, triticonazole, uniconazole, validamycin, valipeniramine, zinc and zinc; nematocides, such as aldicarb, imiciafos, oxamila and fenamifos; bactericides, such as streptomycin; acaricides, such as amitraz, chinomethionate, chlorobenzylate, ciexatin, dicofol, dienochlor, ethoxazole, phenazaquin, fenbutatin oxide, fenpropatrin, fenpyroximate, hexitiazox, propargite, pyridabene and tebufenpirad.
[097] In certain cases, combinations of a compound of this invention with other biologically active compounds or agents (particularly invertebrate pest control) (ie active ingredients)
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48/81 can result in a greater than additive (ie, synergistic) effect. Reducing the amount of active ingredients released into the environment while ensuring effective pest control is always desirable. When synergism of the invertebrate pest control active ingredient occurs at application rates that provide agronomically satisfactory levels of invertebrate pest control application, such combinations can be advantageous to reduce the cost of crop production and decrease the environmental burden.
[098] Compounds of this invention and compositions thereof can be applied to genetically transformed plants to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). Such an application can provide a broader spectrum of plant protection and be advantageous for resistance management. The effect of the exogenously applied invertebrate pest control compounds of this invention may be synergistic with the expressed toxin proteins.
[099] General references for these agricultural protectors (ie insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include the Pesticide Manual, 13th Edition, CDS Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, UK , 2003 and The BioPesticide Manual, 2nd Edition, LG Copping, Ed., British Crop Protection Council, Farnham, Surrey, United Kingdom, 2001.
[0100] For modalities in which one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the Formula 1 compound is typically between about 1: 3000 and about 3,000: 1. Weight ratios between about 1: 300 and about 300: 1 are noted (for example, ratios between about 1:30 and about 30: 1). A person skilled in the art can easily determine, through simple experimentation, the biologically effective amounts of
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49/81 active ingredients needed for the desired spectrum of biological activity. It will be evident that including these additional components can expand the spectrum of controlled invertebrate pests beyond the spectrum controlled by the Formula 1 compound only.
[0101] Table A lists specific combinations of a compound of Formula 1 with other invertebrate pest control agents illustrating the mixtures, compositions and methods of the present invention. The first column of Table A lists the specific invertebrate pest control agents (for example, Abamectin in the first row). The second column of Table A lists the mode of action (if known) or chemical class of invertebrate pest control agents. The third column of Table A lists the weight ratio range modality (s) for rates at which the invertebrate pest control agent can be applied in relation to a Formula 1 compound (for example, 50: 1 to 1:50 abamectin with respect to a Formula 1 compound by weight). Therefore, for example, the first row of Table A specifically shows that a combination of a Formula 1 compound with abamectin can be applied in a weight ratio between 50: 1 and 1:50. The remaining lines in Table A should be interpreted in a similar way. Of even greater importance, Table A lists specific combinations of a Formula 1 compound with other invertebrate pest control agents illustrating the mixtures, compositions and methods of the present invention and includes additional modalities of weight ratio ranges for application rates.
Table A
Invertebrate pest control agent Mode of action or chemical class Typical weight ratio Abamectin macrocyclic lactones 50: 1 to 1:50 Acetamipride neonicotinoids 150: 1 to 1: 200 Amitraz octopamine receptor ligands 200: 1 to 1: 100 Avermectin macrocyclic lactones 50: 1 to 1:50 Azadiractin ecdysone agonists 100: 1 to 1: 120
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Invertebrate pest control agent Mode of action or chemical class Typical weight ratio Beta-Cyfluthrin sodium channel modulators 150: 1 to 1: 200 Bifenthrin sodium channel modulators 100: 1 to 1:10 Buprofezina chitin synthesis inhibitors 500: 1 to 1:50 Cartap nereistoxin analogues 100: 1 to 1: 200 chlorantraniliprole ryanodine receptor ligands 100: 1 to 1: 120 chlorfenapyr mitochondrial electron transport inhibitors 300: 1 to 1: 200 chlorpyrifos cholinesterase inhibitors 500: 1 to 1: 200 Clothianidin neonicotinoids 100: 1 to 1: 400 cyfluthrin sodium channel modulators 150: 1 to 1: 200 cyhalothrin sodium channel modulators 150: 1 to 1: 200 cypermethrin sodium channel modulators 150: 1 to 1: 200 Coromazine chitin synthesis inhibitors 400: 1 to 1:50 Deltamethrin sodium channel modulators 50: 1 to 1: 400 Dieldrin cyclodiene insecticides 200: 1 to 1: 100 Dinotefuran neonicotinoids 150: 1 to 1: 200 Diophenolane molting inhibitor 150: 1 to 1: 200 Emamectin macrocyclic lactones 50: 1 to 1:10 Endosulfan cyclodiene insecticides 200: 1 to 1: 100 Sphenvalerate sodium channel modulators 100: 1 to 1: 400 Etiprol GABA-regulated chlorine channel blockers 200: 1 to 1: 100 Fenotiocarb150: 1 to 1: 200 Fenoxicarb youth hormone simulators 500: 1 to 1: 100 Fenvalerate sodium channel modulators 150: 1 to 1: 200 Fipronil GABA-regulated chlorine channel blockers 150: 1 to 1: 100 Flonicamid200: 1 to 1: 100 Flubendiamide ryanodine receptor ligands 100: 1 to 1: 120 Flufenoxurone chitin synthesis inhibitors 200: 1 to 1: 100 Hexaflumurone chitin synthesis inhibitors 300: 1 to 1:50 Hydramethylnone mitochondrial electron transport inhibitors 150: 1 to 1: 250 Imidacloprid neonicotinoids 1,000: 1 to 1: 1,000 Indoxacarb sodium channel modulators 200: 1 to 1:50 Lambda-cyhalothrin sodium channel modulators 50: 1 to 1: 250 Lufenurone chitin synthesis inhibitors 500: 1 to 1: 250 Metaflumizona200: 1 to 1: 200 Metomila cholinesterase inhibitors 500: 1 to 1: 100 Methoprene youth hormone simulators 500: 1 to 1: 100 Methoxyfenozide ecdysone agonists 50: 1 to 1:50 Nitenpiram neonicotinoids 150: 1 to 1: 200
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Invertebrate pest control agent Mode of action or chemical class Typical weight ratio Nithiazine neonicotinoids 150: 1 to 1: 200 Novaluron chitin synthesis inhibitors 500: 1 to 1: 150 Oxamila cholinesterase inhibitors 200: 1 to 1: 200 Pymetrozine200: 1 to 1: 100 Pyrethrin sodium channel modulators 100: 1 to 1:10 Pyridaben mitochondrial electron transport inhibitors 200: 1 to 1: 100 Piridalila200: 1 to 1: 100 Pyriproxifene youth hormone simulators 500: 1 to 1: 100 Ryanodine ryanodine receptor ligands 100: 1 to 1: 120 Spinetoram macrocyclic lactones 150: 1 to 1: 100 Spinosad macrocyclic lactones 500: 1 to 1:10 Spirodiclofeno lipid biosynthesis inhibitors 200: 1 to 1: 200 Spiromesifeno lipid biosynthesis inhibitors 200: 1 to 1: 200 Tebufenozide ecdysone agonists 500: 1 to 1: 250 Thiacloprid neonicotinoids 100: 1 to 1: 200 Thiamethoxam neonicotinoids 1,250: 1 to 1: 1,000 Tiodicarb cholinesterase inhibitors 500: 1 to 1: 400 Thiosultap-sodium150: 1 to 1: 100 Tralometrine sodium channel modulators 150: 1 to 1: 200 Triazamate cholinesterase inhibitors 250: 1 to 1: 100 Triflumurone chitin synthesis inhibitors 200: 1 to 1: 100 Bacillus thuringiensis biological agents 50: 1 to 1:10 Bacillus thuringiensis delta-endotoxin biological agents 50: 1 to 1:10 NPV (e.g., Gemstar) biological agents 50: 1 to 1:10 (The) ryanodine receptor ligands 100: 1 to 1: 120
(a) 3-bromo-1- (3-chloro-2-pyridinyl) -W- [4-cyano-2-methyl-6 [(methylamino) carbonyl] -phenyl] -1H-pyrazol-5-carboxamide [0102 ] Of importance is the composition of a present invention in which at least one additional biologically active compound or agent is selected from the Invertebrate Pest Control Agents listed in Table A above.
[0103] The weight ratios of a compound, including a Formula 1 compound, to an additional invertebrate pest control agent
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52/81 are typically between 1,000: 1 and 1: 1,000, with one modality between 500: 1 and 1: 500, with another modality between 250: 1 and 1: 200 and another modality between 100: 1 and 1:50.
[0104] Mentioned below, in Table B, are the modalities of specific compositions comprising a compound of Formula 1 and an additional invertebrate pest control agent.
Table B
Mixing No. Compound No. and Invertebrate pest control agent A-l 1 and Abamectin A-2 1 and Acetamipride A-3 1 and Amitraz A-4 1 and Avermectin A-5 1 and Azadiractin A-6 1 and Beta-Cyfluthrin A-7 1 and Bifenthrin A-8 1 and Buprofezina A-9 1 and Cartap A-10 1 and chlorantraniliprole A-l l 1 and chlorfenapyr A-12 1 and chlorpyrifos A-13 1 and Clothianidin A-14 1 and cyfluthrin A-15 1 and cyhalothrin A-16 1 and cypermethrin A-17 1 and Coromazine A-18 1 and Deltamethrin A-19 1 and Dieldrin A-20 1 and Dinotefuran A-21 1 and Diophenolane A-22 1 and Emamectin A-23 1 and Endosulfan A-24 1 and Sphenvalerate A-25 1 and etiprol A-26 1 and Fenotiocarb A-27 1 and phenoxycarb A-28 1 and Fenvalerate A-29 1 and Fipronil A-30 1 and Flonicamid A-31 1 and Flubendiamide A-32 1 and Flufenoxurone
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number ofMixture Compound No. and Invertebrate pest control agent A-33 1 and Hexaflumurone A-34 1 and hydramethylnone A-35 1 and Imidacloprid A-36 1 and Indoxacarb A-37 1 and Lambda-cyhalothrin A-38 1 and Lufenurone A-39 1 and Metaflumizona A-40 1 and metomile A-41 1 and methoprene A-42 1 and methoxyfenozide A-43 1 and Ntenpiram A-44 1 and Nithiazine A-45 1 and Novaluron A-46 1 and Oxamila A-47 1 and Pymetrozine A-48 1 and Pyrethrin A-49 1 and pyridaben A-50 1 and pyridalil A-51 1 and pyriproxifene A-52 1 and Ryanodine A-53 1 and Spinetoram A-54 1 and Spinosad A-55 1 and Spirodiclofeno A-56 1 and Spiromesifeno A-57 1 and Tebufenozide A-58 1 and tiaclopride A-59 1 and thiamethoxam A-60 1 and tiodicarb A-61 1 and thiosultap- sodium A-62 1 and Tralometrine A-63 1 and Triazamate A-64 1 and Triflumurone A-65 1 and Bacillus thuringiensis A-66 1 and Bacillus thuringiensis delta-endotoxin A-67 1 and NPV (e.g., Gemstar) A-68 1 and (The)
(a) 3-bromo-1- (3-chloro-2-pyridinyl) -W- [4-cyano-2-methyl-6 [(methylamino) carbonyl] -phenyl] -1H-pyrazol-5-carboxamide [0105 ] The specific mixtures shown in Table B typically combine a Formula 1 compound with another invertebrate pest agent at the ratios specified in Table A.
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Agronomic Application [0106] Invertebrate pests are controlled in both agronomic and non-agronomic applications by applying the compound of this invention, typically in the form of a composition, in a biologically effective amount to the pest environment, including the agronomic and / or non-agronomic locus of infestation , to the area to be protected, or directly to the pests to be controlled.
[0107] Therefore, the present invention comprises a method for controlling an invertebrate pest in agronomic and / or non-agronomic applications, which comprises bringing the invertebrate pest or its environment into contact with a biologically effective amount of one or more of the compounds of the invention, or with a composition comprising at least one such compound or a composition comprising at least one such compound and a biologically effective amount of at least one additional compound or biologically active 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 in which the additional active compound is present in the same granule as the compound of the invention or in granules separate from those of the compound of the invention.
[0108] 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 the seed of the crop before planting, to foliage (for example, leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth medium before or after the crop is planted.
[0109] One method of a contact method is by spraying. Alternatively, a granular composition comprising a compound of the
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55/81 invention can be applied to the foliage of the plant or to the soil. The compound of this invention can also be delivered effectively through plant absorption by placing the plant in contact with a composition comprising a compound of this invention applied as a soil drench of a liquid formulation, a granular formulation to the soil, a treatment nursery box or a transplant dive. Of importance is a composition of the present invention in the form of a liquid soil-soak formulation. Also important is a method for controlling an invertebrate pest that comprises bringing the invertebrate pest or its environment into contact with a biologically effective amount of a compound of the present invention or with a composition that comprises a biologically effective amount of a compound of the present invention . Of additional importance is this method in which the environment is the soil and the composition is applied to the soil as a soil-soak formulation. Of additional importance are the compounds of this invention that are also effective by localized application to the infestation locus. Other contact methods include applying a compound or composition of the invention by direct and residual sprays, aerial sprays, gels, seed coatings, microencapsulations, systemic absorption, baits, ear tags, boluses, smokers, fumigants, aerosols, dust and many others. One embodiment of a contact method is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the invention. The compound of this invention can also be impregnated with materials to make invertebrate control devices (for example, insect entanglement).
[0110] Compound 1 of this invention is also useful in seed treatments to protect seeds from invertebrate pests. In the context of the present description and claims, the treatment of a seed
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56/81 means contacting the seed with a biologically effective amount of a compound of this invention, which is typically formulated as a composition of the invention. This seed treatment protects the seed from invertebrate soil pests and, in general, can also protect roots and other plant parts in contact with the developing seedling soil from the germinating seed. Seed treatment can also provide foliage protection by translocation of the compound of this invention or a second active ingredient in the developing plant. Seed treatments can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate. Representative examples include those that express proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxin, or those that express herbicide resistance, such as glyphosate acetyltransferase, which provides glyphosate resistance.
[0111] A seed treatment method is by sprinkling or spraying the seed with a compound of the invention (i.e., as a formulated composition) before sowing the seeds. Compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore, typically, a seed coating composition of the present invention comprises a biologically effective amount of a Formula 1 compound and a film-forming or adhesive agent. The seed can be coated by spraying a fluidizable suspension concentrate directly into a seed revolution bed and then drying the seeds. Alternatively, other types of formulation, such as wet powders, solutions, suspoemulsions, emulsifiable concentrates and water emulsions can be sprayed onto the seed. This process is particularly useful for applying film coatings to seeds. Various machines and processes
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57/81 coating is available to an individual skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and references mentioned therein.
[0112] The treated seed typically comprises a compound of the present invention in an amount of about 0.1 g to 1 kg per 100 kg of seed (i.e., from about 0.0001 to 1% by weight of the seed before treatment). A fluidizable suspension formulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingredient, from about 0.5 to about 30% of a film-forming adhesive, from about 0, 5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and / or dye, from 0 to about 2% of a defoaming agent, of 0 the stem of 1% of a condom, and 0 to about 75% of a volatile liquid diluent.
[0113] Compound 1 of this invention can be incorporated into a bait composition that is consumed by an invertebrate pest or used in a device such as a trap, bait solution, and the like. Such a bait composition may be in the form of granules comprising (a) active ingredients, namely, a biologically effective amount of a Formula 1 compound, an N-oxide, or salt thereof; (b) one or more food materials; optionally (c) an attractive, and optionally (d) one or more humectants. Bait granules or compositions are important which comprise between about 0.001 to 5% of active ingredients, about 40 to 99% of food and / or attractive material; and, optionally, about 0.05 to 10% of humectants, which are effective in controlling soil invertebrate pests at very low application rates, particularly at doses of active ingredient that are lethal by ingestion, rather than by direct contact . Some food materials can function both as a food source and
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58/81 as an attractive. Food materials include carbohydrates, proteins and lipids. Examples of food materials are vegetable flour, sugar, starches, animal fat, vegetable oil, yeast extracts and milk solids. Examples of attractants are odorants and flavorings, such as fruit or plant extracts, perfume, or another animal or plant component, pheromones or other agents known to attract a target invertebrate pest. Examples of humectants, that is, moisture retaining agents, are glycols and other polyols, glycerin and sorbitol. Of importance is a bait composition (and a method that uses such a bait composition) used to control at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. A device for controlling an invertebrate pest may comprise the present bait composition and a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to allow the invertebrate pest to pass through the opening so that the invertebrate pest may have access to the bait composition from a location outside the housing, and where the housing is additionally adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.
[0114] Compound 1 of this invention can be applied without other adjuvants, but more often the application will be of a formulation comprising one or more active ingredients with suitable vehicles, diluents, and surfactants and possibly in combination with a food that depends end use contemplated. An ordering method involves spraying a water dispersion or refined oil solution of a compound of the present invention. Combinations with spray oils, spray oil concentrations, dispenser adhesives, adjuvants, other solvents, and synergists, such as piperonyl butoxide, often enhance the effectiveness of the compound. For non-agronomic uses, such sprinklers
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59/81 can be applied from spray containers, such as a can, bottle or other container, either by means of a pump or by releasing them from a pressurized container, for example, an aerosol spray can pressurized. Such spray compositions can take various forms, for example, sprinkles, mists, foams, smoke or mist. Such spray compositions can therefore further comprise propellants, foaming agents, etc. according to each case. Of importance is a spray composition comprising a biologically effective amount of a compound or a composition of the present invention and a vehicle. One embodiment of such a spray composition comprises a biologically effective amount of a compound or composition of the present invention and a propellant. Representative 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 aforementioned. Of importance is a spray composition (and a method that uses such a spray composition dispensed from a spray container) used to control at least one invertebrate pest selected from the group consisting of mosquitoes, black flies, stable flies, deer, horse flies, wasps, yellow jacket wasps, hornets, bedbugs, spiders, ants, flies, and the like, including individually or in combination.
NON-AGRONOMIC AND ANIMAL HEALTH UTILITY [0115] Non-agronomic uses refer to invertebrate pest control in areas other than crop plant fields. Non-agronomic uses of the present compounds and compositions include the control of invertebrate pests in stored grains, beans and other food products, and in textile products such as clothing and carpets. Uses not
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60/81 agronomic aspects of the present compounds and compositions also include invertebrate pest control in ornamental plants, forests, in gardens, along roads and shoulders, and in peat, such as lawns, golf courses and pastures. Non-agronomic uses of the present compounds and compositions also include invertebrate pest control in houses and other buildings that can be occupied by humans and / or companions, farm, ranch, zoo or other animals. Non-agronomic uses of the present compound and compositions also include pest control, such as termites that can damage wood or other structural materials used in construction.
[0116] Non-agronomic uses of the present compound 1 and compositions also include protecting the health of humans and animals by controlling invertebrate pests that are parasitic or transmit infectious diseases. Animal parasite control includes controlling external parasites that are parasitic on the surface of the host animal's body (eg, shoulders, armpits, abdomen, inner thighs) and internal parasites that are parasitic on the interior of the host animal's body (eg stomach, intestine, lung, veins, under the skin, lymphatic tissue). External disease-carrying or parasitic pests include, for example, insects, bedbugs, lice, mosquitoes, flies, mites and fleas. Internal parasites include heartworms, tapeworms and intestinal worms. Compounds and compositions of the present invention are particularly suitable for combating disease-transmitting pests or external parasites. Compound 1 and the compositions of the present invention are suitable for the systemic and / or non-systemic control of parasite infestation or infection in animals.
[0117] Compound 1 and the compositions of the present invention are suitable for combating parasites that infest animal subjects, including
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61/81 those wild, livestock and farm animals such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, chickens, turkeys, ducks, geese and bees (for example, bred for meat, milk , butter, eggs, hair, leather, feathers and / or wool). By combating parasites, fatalities and reduced performance (in terms of meat, milk, wool, skins, eggs, honey, etc.) are reduced, so that the application of a composition comprising a compound of the present invention allows the creation more economic and simple use of animals.
[0118] Compound 1 and the compositions of the present invention are especially suitable for combating parasites that infest accompanying animals and pets (e.g. dogs, cats, pet birds and aquarium fish), research animals and experiments ( eg hamsters, guinea pigs, rats and mice), as well as animals raised for / in zoos, wild habitats and / or circuses.
[0119] In one embodiment of this invention, the animal is preferably a vertebrate, and more preferably, a mammal, a bird, or a fish. In a particular embodiment, the animal subject is a mammal (including hominids, such as humans). Other mammalian subjects include primates (for example, monkeys), cattle (for example, cattle or dairy cows), pigs (for example, fattening pigs or pigs), sheep (for example, goats or sheep), equines (for example, horses), canines (e.g. dogs), felines (e.g. domestic cats), camels, deer, donkeys, buffaloes, antelopes, rabbits and rodents (e.g. guinea pigs, squirrels, rats, mice, domestic rodents, and hamsters). Birds include Anatidae (swans, ducks and geese), Columbidae (eg pigeons), fasianidae (eg partridges, lizards and turkeys), Thesienidae (eg domestic chickens), Psittacines (eg parakeets,
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62/81 macaws, and parrots), hunting birds, and Struthioniformes (for example, ostriches).
[0120] Birds treated or protected by the compounds of the invention can be associated with commercial or non-commercial poultry. These include Anatidae, as swans, geese, and ducks, Columbidae, as pigeons and domestic pigeons, fasianidae, as partridges, lizards and turkeys, Thesienidae, as domestic chickens, and Psittacinas, as parakeets, macaws, and parrots bred for the pets or collector, among others.
[0121] For the purposes of the present invention, the term fish should be understood to include, without limitation, the Teleosti grouping of fish, that is, teleost. Both the order of salmoniformes (which includes the family Salmonidae) and the order of Perciformes (which includes the family Centrarchidae) are contained in the Teleosti group. Examples of potential fish containers include Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae, among others.
[0122] Other animals are also contemplated to benefit from inventive methods, including marsupials (such as kangaroos), reptiles (such as farm turtles), and other economically important domestic animals for which inventive methods are safe and effective in the treatment or prevention of infection or parasite infestation.
Animal Health Pests / Parasites [0123] Examples of invertebrate parasitic pests controlled by administering a pesticide effective amount of a compound of this invention to an animal to be protected include ectoparasites (arthropods, acarines, etc.) and endoparasites (helminths, for example , nematodes, trematodes, cestodes, acanthocephalus, etc.).
[0124] The disease or group of diseases described, in general, as
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63/81 helminthiasis is due to the infection of an animal host with parasitic worms known as helminths. The term helminths should include nematodes, trematodes, ketones and acanthocephalus. Helminthiasis is a prevalent and serious economic problem with domesticated animals, such as pigs, sheep, horses, cattle, goats, dogs, cats and birds.
[0125] Among the Helminths, the group of worms described as nematodes causes the infection to be widely distributed and, occasionally, serious in several species of animals. Nematodes that are contemplated to be treated by the compounds of this invention and by the inventive methods include, without limitation, the following genera: Acanthocheilonema,
Aelurostrongylus, Ancylostoma, Angiostrongylus, Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema, Diphyllobotrium, Dirofilaria, Dracunculis, Hercules, Hercules, Enterobius, Necator, Nematodirus, Oesofagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca, Stefanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichinella, Trichone and Trichone
[0126] Among the above, the most common genera of nematodes that infect the animals referred to above are Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Oesofagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillary, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Some of these, such as Nematodirus, Cooperia and Oesofagostomum primarily attack the intestinal tract while others, such as Haemonchus and Ostertagia, are more prevalent in the stomach while others, such as Dictyocaulus are found in the lungs. Still, other parasites
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64/81 can be located in other tissues, such as the heart and blood veins, subcutaneous and lymphatic tissue, and the like.
[0127] Trematodes that are contemplated to be treated by compound 1 of this invention and by the inventive methods include, without limitation, the following genera: Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus and Schistosoma.
[0128] Cestodes that are contemplated to be treated by compound 1 of this invention and by the inventive methods include, without limitation, the following genera: Diphyllobotrium, Diplydium, Spirometra and Taenia.
[0129] The most common genera of parasites in the human gastrointestinal tract are Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris, and Enterobius. Other genera of parasites of medical importance that are found in blood or other tissues and organs outside the gastrointestinal tract are the filarial worms, such as Wuchereria, Brugia, Onchocerca and Loa, as well as Dracunculus and extra intestinal stages of the Strongyloides and Trichinella intestinal worms.
[0130] Various other genera and species of helminths are known in the art, and are also contemplated to be treated by the compounds of the invention. These are listed in great detail in Textbook of Veterinary Clinicai Parasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co., Philadelphia, PA, USA .; Helminths, Arthropods and Protozoa, (6th Edition of Monnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby, The Williams and Wilkins Co., Baltimore, Md.
[0131] It is also contemplated that the compound of the invention is effective against various animal ectoparasites, for example, arthropod ectoparasites of mammals and birds, although it is recognized that some arthropods may also be endoparasites.
[0132] Therefore, insect pests and mites include, for example,
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65/81 biting insects, such as flies and mosquitoes, mites, bedbugs, lice, fleas, hemiptera, parasitic worms and the like.
[0133] Adult flies include, for example, the horn fly or Haematobia irritans, the horse fly or Tabanus spp., The stable fly or Stomoxys calcitrans, the black fly or Simulium spp., The deer fly or Chrysops spp ., the louse fly or Melofagus ovinus, the tsetse fly or Glossina spp. Larvae of parasitic flies include, for example, the berne (Oestrus ovis and Cuterebra spp.), A blowfly or faenicia spp., The worm larva or Cochliomyia hominivorax, the larvae cattle or Hypoderma spp., The wool worm and the Gastrophilus of horses. Mosquitoes include, for example, Culex spp., Anopheles spp., And Aedes spp.
[0134] Mites include Mesostigmata spp. for example, mesostigmats, such as the chicken mite, Dermanyssus gallinae; itchy or eschar mites, such as Sarcoptidae spp. for example, Sarcoptes scabiei; scabies mites, such as Psoroptidae spp., including Chorioptes bovis and Psoroptes ovis; mite larvae, for example, Trombiculidae spp., for example, the North American larva, Trombicula alfreddugesi.
[0135] Bedbugs include, for example, soft bedbugs, including Argasidae spp. for example, Argas spp. and Ornithodoros spp .; ticks, including Ixodidae spp., for example, Rhipicefalus sanguineus, Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Ixodes scapularis and Boophilus spp.
[0136] Lice include, for example, sucking lice, for example, Menopon spp. and Bovicola spp .; biting lice, for example, Haematopinus spp., Linognathus spp. and Solenopotes spp.
[0137] Fleas include, for example, Ctenocefalides spp., Such as the dog flea (Ctenocefalides canis) and the cat flea (Ctenocefalides felis); Xenopsylla spp., Such as the eastern rat flea (Xenopsylla cheopis); and
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Pulex spp., Like the human flea (Pulex irritans).
[0138] Hemiptera include, for example, Cimicidae or, for example, the common stink bug (Cimex lectularius); Triatominae spp., Including triatomids also known as barbers; for example, Rhodnius prolixus and Triatoma spp.
[0139] In general, flies, fleas, lice, mosquitoes, insects, mites, bedbugs and helminths cause tremendous losses to the livestock and pet sectors. Arthropod parasites are also a disease to humans and can act as transmitters for disease-causing organisms in humans and animals.
[0140] Several other arthropod and ectoparasitic pests are known in the art and are also contemplated to be treated by compound 1 of the invention. These are listed in more detail in Medical and Veterinary Entomology, D. S. Kettle, John Wiley & Sons, New York, USA and Toronto, Canada; Control of Arthropod Pests of Livestock: A Review of Technology, RO Drummand, JE George, and SE Kunz, CRC Press, Boca Raton, Fla., USA [0141] It is also contemplated that compound 1 and compositions of this invention may be effective against various protozoan endoparasites of animals, including those summarized in Table 3, as follows.
Table 3
Exemplifying parasitic protozoa and associated human diseases
Phylum Subphile Representative gender Human disease or disorder Sarcomastigophora (with flagella, pseudopodia, or both) Mastigophora (Flagella) Leishmania Visceral, skin and mucocutaneous infection Trypansoma Sleeping sickness Chagas disease Giardia Diarrhea Trichomonas VaginitisSarcodina (pseudopodia) Entamoeba Dysentery, liver abscess Dientamoeba Colitis
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Phylum Subphile Representative gender Human disease or disorder Naegleriasis and acantameba Ulcers of the central nervous system and cornea Babesia Babesíese Apicomplexa (apical complex)Plasmid Malaria Isospora Diarrhea Sarcocystis Diarrhea Cryptosporidum Diarrhea Toxoplasma Toxoplasmosis Eimeria Coccidiosis in chicken MicrosporaEnterocytozoon Diarrhea Ciliaphora (with lashes)Balantidium Dysentery Not classifiedPneumocystosis Pneumonia
[0142] In particular, compound 1 of this invention is effective against ectoparasites, including: flies, such as Haematobia (Lyperosia) irritans (horn fly), Stomoxys calcitrans (stable fly), Simulium spp. (black fly), Glossina spp. (tsetse flies), Hydrotaea irritans (flower fly), Musca autumnalis (face fly), Musca domestica (house fly), Morellia simplex (sweat fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green blowfly), Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasal fly), Culicoides spp. (mosquitoes), Hippobosca equine, Gastrophilus instestinalis, Gastrophilus haemorrhoidalis and Gastrophilus naslis; lice, with Bovicola (Damalinia) bovis, Bovicola equi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger, Lignonathus setosus and Trichodectes canis; keds flies, such as Melofagus ovinus; mites, such as Psoroptes spp., Sarcoptes scabei, Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear mites); stink bugs, such as Ixodes spp., Boophilus spp., Rhipicefalus spp., Amblyomma spp., Dermacentor spp., Hyalomma spp. and Haemaphysalis spp .; and fleas, such as Ctenocefalides felis (cat flea) and Ctenocefalides canis (dog flea).
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68/81
Animal health mixtures [0143] Biologically active compound 1 or agents useful in the compositions of the present invention include organophosphate pesticides. This class of pesticide has a very broad activity as insecticides and, in certain instances, anthelmintic activity. Organophosphate pesticides include, for example, dicrotophos, terbufos, dimetoate, diazinon, disulfoton, trichlorfon, azymphos-methyl, chlorpyrifos, malation, oxidemeton-methyl, metamidophos, acephate, ethyl paration, methyl paration, mevinfos, forato, carbofention. It is also contemplated to include combinations of the methods and compounds of the invention with carbamate-type pesticides, including, for example, carbaryl, carbofuran, aldicarb, molinate, metomyl, carbofuran, etc., as well as combinations with organochlorine-type pesticides. It is also contemplated to include combinations with biological pesticides, including repellents, pyrethrins (as well as synthetic variations of them, for example, aletrine, resmethrin, permethrin, tralometrine), and nicotine, which is often used as an acaricide. Other combinations contemplated are with varied pesticides, including: bacillus thuringensis, chlorobenzylate, formamidines (for example, amitraz), copper compounds (for example, copper hydroxide and cupric oxychloride sulfate), cyfluthrin, cypermethrin, dicofol, endosulfan, esphenfenvalerate, fenvalerate, lambda-cyhalothrin, methoxychlor and sulfur.
[0144] Additional biologically active compounds or agents selected from anthelmintics known in the art, such as, for example, avermectins (for example, ivermectin, moxidectin, milbemycin), benzimidazoles (for example, albendazole, triclabendazole), salicylanilides (for example , closantel, oxyclozanide), substituted phenols (e.g. nitroxynyl), pyrimidines (e.g. pirantel), imidazothiazoles (e.g. levamisole) and praziquantel.
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69/81 [0145] Other biologically active compounds or agents useful in the compositions of the present invention can be selected from Insect Growth Regulators (IGRs) and Juvenile Hormone Analogues (JHAs), such as diflubenzuron, triflumuron, fluazuron, cyromazine, methoprene , etc., thereby providing both initial and continuous control of parasites (at all stages of insect development, including eggs) in the animal subject, as well as in the animal subject's environment.
[0146] Biologically active compounds or agents useful in the compositions of the present invention selected from the antiparasitic class of avermectin compounds are of importance. As stated above, the avermectin family of compounds is a series of very potent antiparasitic agents known to be useful against a wide spectrum of endoparasites and ectoparasites in mammals.
[0147] A preferred compound for use in the scope of the present invention is ivermectin. Ivermectin is a semi-synthetic derivative of avermectin and is generally produced as a mixture of at least 80% 22,23-dihydroavermectin Bla and less than 20% 22,23-dihydroavermectin Blb. Ivermectin is disclosed in US 4,199,569.
[0148] Abamectin is an avermectin that is presented as Avermectin Bla / Blb in US 4,310,519. Abamectin contains at least 80% avermectin Bla and no more than 20% avermectin Blb.
[0149] Another avermectin is Doramectin, also known as 25-Cyclohexyl-avermectin Bi. The structure and preparation of Doramectin is shown in US 5,089,480.
[0150] Another preferred avermectin is Moxidectin. Moxidectin, also known as LL-F28249 alpha, is known from US 4,916,154.
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70/81 [0151] Another preferred avermectin is Selamectin. Selamectin is 25-cyclohexyl-25-de (1-methylpropyl) -5-deoxy-22,23-dihydro5- (hydroxyimino) -vermectin Bi monosaccharide.
[0152] Milbemycin, or B41, is a substance that is isolated from the fermentation broth of a milbemycin-producing strain of Streptomyces. The microorganism, fermentation conditions and isolation procedures are more fully described in US 3,950,360 and US 3,984,564.
[0153] Emamectin (4-deoxy-4-epi-methylaminoavermectin Bl), which can be prepared as described in US 5,288,710 or US 5,399,717, is a mixture of two homologues, 4-deoxy-4-epimethylaminoavermectin Bla and 4-deoxy-4-epi-methylaminoavermectin Blb. Preferably, an Emamectin salt is used. Non-limiting examples of Emamectin salts that can be used in the present invention include the salts described in US 5,288,710, for example, salts derived from benzoic acid, substituted benzoic acid, benzenesulfonic acid, citric acid, phosphoric acid, tartaric acid, maleic acid, and the like. Most preferably, the emamectin salt used in the present invention is emamectin benzoate.
[0154] Eprinomectin is chemically known as 4-epiacetylamino-4-deoxy-avermectin Bl. Eprinomectin was specifically developed for use in all classes of livestock and age groups. It was the first avermectin to show broad-spectrum activity against both endo and ectoparasites while also leaving minimal residues in meat and milk. It has the added advantage of being highly potent when delivered topically.
[0155] The composition of the present invention optionally comprises combinations of one or more of the following compounds
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71/81 antiparasitic: The imidazo [1,2-b] pyridazine compounds, as described by US patent application serial no. 11 / 019,597, deposited on December 22, 2004; compounds 1- (4-mono and dihalomethylsulfonylphenyl) -2-acylamino-3fluoropropanol, as described by US Patent Application Serial No. 11 / 018,156, filed December 21, 2004; derivatives of trifluoromethanesulfonanilide oxime ether, as described by US Patent Application Serial No. 11 / 231,423, filed September 21, 2005; and derivatives of n - [(phenyloxy) phenyl] -1,1,1-trifluoromethanesulfonamide en [(phenylsulfanyl) phenyl] -1,1,1-trifluoromethanesulfonamide, as described in US provisional patent application serial number 60 / 688,898 , filed on June 9, 2005.
[0156] The compositions of the present invention can also comprise a tramtodicide. Suitable trematodicides include, for example, Triclabendazole, Fenbendazole, Albendazole, Clorsulon and Oxibendazole. It will be noted that the combinations above may also include combinations of antibiotic, antiparasitic and active antitrematode compounds.
[0157] In addition to the above combinations, it is also contemplated to provide combinations of the methods and compounds of the invention, as described in the present invention, with other remedies for animal health, such as trace elements, anti-inflammatory, anti-infectious, hormones, dermatological preparations , including antiseptics and disinfectants, and immunobiologicals, such as vaccines and antisera for disease prevention.
[0158] For example, such anti-infectives include one or more antibiotics that are optionally co-administered during treatment with the use of compounds or methods of the invention, for example, in a combined composition and / or in separate dosage forms. Antibiotics known in the art for this purpose include, for example, those listed in the present document below.
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72/81 [0159] A useful antibiotic is Florfenicol, also known as D (treo) -l- (4-methylsulfonylphenyl) -2-dichloroacetamido-3-fluoro-1-propanol. Another preferred antibiotic compound is D- (threo) -1- (4-methylsulfoniphenyl) -2difluoroacetamido-3-fluoro-1-propanol. Another useful antibiotic is thiamphenicol. The processes for making these antibiotic compounds, and intermediates useful in such processes, are described in US 4,311,857; US 4,582,918; US 4,973,750; US 4,876,352; US 5,227,494; US 4,743,700; US 5,567,844; US 5,105,009; US 5,382,673; US 5,352,832; and US 5,663,361. Other florfenicol and / or prodrug analogs have been disclosed and such analogs can also be used in the compositions and methods of the present invention (see, for example, US patent application publication No. 2004/0082553, and patent application US Serial No. 11 / 016,794).
[0160] Another useful antibiotic compound is Tilmicosin. Tilmicosin is a macrolide antibiotic that is chemically defined as 20-dihydro-20desoxy-20- (c / s-3,5-dimethylpiperidin-1-yl) -desmicosin and which is disclosed in US 4,820,695.
[0161] Another antibiotic useful for use in the present invention is Tulathromycin. Tulathromycin can be identified as 1l-oxa-6azacyclopentadecan-15-one, 13 - [(2,6-dideoxy-3-C-methyl-3-0-methyl-4-C [(propylamino) methyl] -alpha- L-ribohexopyranosyl] oxy] -2-ethyl-3,4,10-trihydroxy3,5,8,10,12,14-hexamethy-1 -11 - [[3,4,6-trideoxy-3- ( dimethylamino) -beta-D-xylohexopyranosyl] oxy] -, (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R) .Tulothromycin can be prepared according to the procedures presented in the patent publication US No. 2003/0064939 Al.
[0162] Additional antibiotics for use in a present invention include cephalosporins such as, for example, Ceftiofur, Cefquinome, etc. The concentration of cephalosporin in the formulation of the present invention optionally ranges from about 1 mg / ml to 500 mg / ml.
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73/81 [0163] Another useful antibiotic includes fluoroquinolones, such as, for example, Enrofloxacin, Danofloxacin, Difloxacin, Orbifloxacin and Marbofloxacin. In the case of Enrofloxacin, it can be administered at a concentration of about 100 mg / ml. Danofloxacin can be present at a concentration of about 180 mg / ml.
[0164] Other useful macrolide antibiotics include compounds from the ketolide classes, or, more specifically, azalides. Such compounds are described in, for example, US 6,514,945, US 6,472,371, US 6,270,768, US 6,437,151, US 6,271,255, US 6,239,112, US 5,958,888, US 6,339,063 and US 6,054,434.
[0165] Other useful antibiotics include tetracyclines, particularly chloretetracycline and oxytetracycline. Other antibiotics may include β-lactams, such as penicillins, for example, penicillin, ampicillin, amoxicillin, or a combination of amoxicillin with clavulanic acid or other beta lactamase inhibitors.
Animal Health Formulation / Application [0166] Non-agronomic applications in the veterinary sector are carried out by conventional means, such as enteral administration in the form of, for example, tablets, capsules, drinks, bath preparations, granules, pastes, boluses, procedures by feeding medium, or suppositories; or by parenteral administration, such as by injection (including intramuscular, subcutaneous, intravenous, intraperitoneal) or implants; by nasal administration; by topical administration, for example, in the form of immersion or diving, spraying, washing, powder coating, or application to a small area of the animal, and through articles such as collars, ear tags, tail bands, limb bands or halters comprising compounds or compositions of the present invention.
[0167] Compound 1 of the present invention, or a combination
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74/81 such compound, can be administered directly to the animal subject and / or indirectly by applying it to the local environment in which the animal lives (such as bed, closed areas, or similar). Direct administration includes contact with the skin, fur, or feathers of an animal subject with the compound, or by feeding or injecting the compound into the animal.
[0168] Compound 1 of the present invention can be administered in controlled release form, for example, in a subcutaneous slow release formulation, or in the form of a controlled release device spun to an animal, such as an anti-flea collar. Collars for the controlled release of an insecticidal agent for long-term protection against flea infestation in a pet are known in the art and are described, for example, in US 3,852,416, US 4,224,901, US 5,555. 848 and US 5,184,573.
[0169] Typically, a parasiticidal composition according to the present invention comprises a mixture of a compound of Formula 1 with one or more pharmaceutically or otherwise acceptable carriers comprising excipients and auxiliaries selected in relation to the intended route of administration (for example , oral, topical or parenteral administration, as an injection) and, according to standard practice. In addition, a suitable vehicle is selected based on compatibility with one or more active ingredients in the composition, including such considerations as stability in relation to pH and moisture content. Therefore, a composition for protecting an animal from an invertebrate parasitic pest comprising an effective amount against parasites of a compound of the invention and at least one vehicle is of importance.
[0170] For parenteral administration, including intravenous, intramuscular and subcutaneous injection, a compound of the present invention can be formulated in suspension, solution or emulsion in oily vehicles
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75/81 or aqueous, and may contain auxiliary compounds, such as suspending, stabilizing and / or dispersing agents. The compounds of the present invention can also be formulated for bolus injection or continuous infusion. Pharmaceutical compositions for injection include aqueous solutions of water-soluble forms of active ingredients (for example, a salt of an active compound), preferably in physiologically compatible buffers containing other excipients or auxiliaries, as is known in the pharmaceutical formulation art. In addition, suspensions of the active compound can be prepared in a lipophilic vehicle. Suitable lipophilic vehicles include fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate and triglycerides, or materials, such as liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Injection formulations can be presented in unit dosage form, for example, in ampoules or in multiple dose containers. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, for example, sterile water, without pyrogen, before use.
[0171] In addition to the formulations described above, compound 1 of the present invention can also be formulated as a depot preparation. Such long-acting formulations can be administered by implantation (for example, subcutaneously or intrasmuscularly) or by intramuscular or subcutaneous injection. The compound 1 of the present invention can be formulated for that route of administration with suitable polymeric or hydrophobic materials (for example, in an emulsion with a pharmaceutically acceptable oil), with ion exchange resins, or as a poorly soluble derivative such as, without limitation , a little soluble salt.
[0172] For administration by inhalation, compound 1 of
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The present invention can be delivered in the form of an aerosol spray using a pressurized package or a nebulizer and a suitable propellant, for example, without limitation, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit can be controlled by providing a valve to deliver a metered amount. Capsules and cartridges of, for example, gelatin for use in an inhaler or insufflator can be formulated containing a powder mixture of the compound and a suitable powder base, such as lactose or starch.
[0173] Compound 1 of the present invention has been found to have favorable pharmacokinetic and pharmacodynamic properties that provide systemic availability from oral administration and ingestion. Therefore, after ingestion by the animal to be protected, parasitically effective concentrations of compounds of the invention in the bloodstream protect the treated animal from blood sucking pests such as fleas, bedbugs and lice. Therefore, it is important for a composition to protect an animal from an invertebrate parasitic pest in a form for oral administration (ie, comprising, in addition to a parasitically effective amount of a compound of the invention, one or more selected vehicles of binders and fillers suitable for oral administration and feed concentrate vehicles).
[0174] For oral administration in the form of solutions (the form most readily available for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, rumen retention and food / water / stone blocks , a compound of the present invention can be formulated with binders / fillers known in the art for being suitable for compositions for oral administration, such as sugars and sugar derivatives (for example, lactose, sucrose, mannitol, sorbitol), starch (for example, starch maize, wheat starch, rice starch, potato starch), cellulose and derivatives
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77/81 (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (eg, magnesium stearate), disintegrating agents (eg, cross-linked polyvinylpyrrolidone, agar, alginic acid) and dyes or pigments can be added. Pastes and gels also often contain adhesives (eg, acacia, alginic acid, bentonite, cellulose, xanthan gum, magnesium silicate and colloidal aluminum) to help keep the composition in contact with the oral cavity and not be easily ejected .
[0175] If the parasiticidal compositions are in the form of feed concentrates, the vehicle is typically selected from high-performance feed, feed cereals or protein concentrates. Such compositions that contain feed concentrate may, in addition to the parasiticidal active ingredients, comprise additives that promote animal health or growth, improving the quality of the animals' meat for cutting or, otherwise, being useful for the animal's breeding. Such additives may include, for example, vitamins, antibiotics, chemotherapy, bacteriostats, fungistats, coccidiostats and hormones.
[0176] The Formula 1 compound can also be formulated in rectal compositions, such as suppositories or retention enemas, using, for example, conventional suppository bases, such as cocoa butter or other glycerides.
[0177] Formulations for topical administration are typically in the form of a powder, cream, suspension, spray, emulsion, foam, paste, aerosol, ointment, ointment or gel. More typically, a topical formulation is a water-soluble solution, which can be in the form of a concentrate that is diluted before use. Parasiticidal compositions suitable for topical administration typically comprise a
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78/81 composed of the present invention and one or more topically suitable vehicles. In applications of a parasiticidal composition topically outside an animal as a line or a point (i.e., spot treatment), the active ingredient migrates across the animal's surface to cover most or all of its outer surface area. As a consequence, the treated animal is particularly protected from invertebrate pests that feed on the animal's epidermis, such as bedbugs, fleas and lice. Therefore, topically administered formulations often comprise at least one organic solvent to facilitate transport of the active ingredient through the skin and / or penetration into the animal's epidermis. Vehicles in such formulations include propylene glycol, paraffins, aromatics, esters, such as isopropyl myristate, glycol ethers, alcohols, such as ethanol, n-propanol, 2-dodecanol octyl or oleyl alcohol; solutions in monocarboxylic acid esters, such as isopropyl myristate, isopropyl palmitate, lauric acid oxalic pester, oleic acid oleyl ester, oleic acid decyl ester, hexyl laurate, oleyl oleate, decyl oleate, caproic acid esters saturated fatty alcohols of C12-C18 chain length; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, adipic acid diisopropyl ester, di-n-butyl adipate or solutions of aliphatic acid esters, for example, glycols. It may be advantageous for a crystallization inhibitor or dispersant known to the pharmaceutical or cosmetic industry to also be present.
[0178] A spill formulation can also be prepared for the control of parasites in an animal of agricultural value. The pouring formulations of this invention can be in the form of a liquid, powder, emulsion, foam, paste, aerosol, ointment, ointment or gel. Typically, the pour formulation is liquid. These pouring formulations can be applied effectively to sheep, cattle, goats, other ruminants,
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79/81 camelids, pigs and horses. The pouring formulation is typically applied when pouring into one or several lines or at a point on the dorsal midline (back) or shoulders of an animal. More typically, the formulation is applied by pouring it along the animal's back, following the spine. The formulation can also be applied to the animal by other conventional methods, including a material impregnated through at least a small area of the animal, or applied using a commercially available applicator, by means of a syringe, by spraying or by using a spray chamber. The pouring formulations include a carrier and can also include one or more additional ingredients. Examples of additional ingredients are stabilizers, such as antioxidants, spreading agents, preservatives, adhesion promoters, active solubilizers, such as oleic acid, viscosity modifiers, UV blockers or absorbents, and dyes. Surface active agents, including anionic, cationic, nonionic and ampholytic surface active agents, can also be included in these formulations.
[0179] The formulations of this invention typically include an antioxidant, such as BHT (butylated hydroxy toluene). The antioxidant is, in general, present in quantities of 0.1 to 5% (w / vol). Some of the formulations require a solubilizer, such as oleic acid, to dissolve the active agent, particularly if spinosad is used. The spreading agents used in these pouring formulations are: IPM, IPP, C12-C18 caprylic / capric acid esters, saturated fatty alcohols, oleic acid, oleyl ester, ethyl oleate, triglycerides, silicone oils and DPM. The pouring formulations of this invention are prepared according to known techniques. Where the pouring formulation is a solution, the parasiticide / insecticide is mixed with the excipient or vehicle, with the use of heat and agitation where required. Auxiliary or additional ingredients can be
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80/81 added to the active agent and vehicle mixture, or can be mixed with the active agent prior to the addition of the vehicle. If the pouring formulation is an emulsion or suspension, these formulations are prepared in a similar manner using known techniques.
[0180] Other delivery systems for relatively hydrophobic pharmaceutical compounds can be employed. Liposomes and emulsions are well-known examples of delivery vehicles or vehicles for hydrophobic drugs. In addition, organic solvents such as dimethyl sulfoxide can be used, if necessary.
[0181] For agronomic applications, the application rate required for effective control (ie biologically effective amount) will depend on such factors as the species of invertebrates to be controlled, the life cycle of the pest, the stage of life, its size , location, time of year, host culture or animal, feeding behavior, crossing behavior, ambient humidity, temperature and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredients per hectare are enough to control pests in agronomic ecosystems, but an amount as low as 0.0001 kg / hectare can be enough or as as low as 8 kg / hectare may be required. For non-agronomic applications, effective use will vary from about 1.0 to 50 mg / square meter, but an amount as low as 0.1 mg / square meter may be sufficient or as much as 150 mg / square meter may be required . A person skilled in the art can easily determine the biologically effective amount needed for the desired level of invertebrate pest control.
[0182] In general, for veterinary use, a Formula 1 compound is administered in an effective amount as a parasiticide to an animal to be protected from invertebrate parasitic pests. An effective amount eat
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81/81 parasiticide is the amount of active ingredient needed to achieve an observable effect that decreases the occurrence or activity of the target invertebrate parasite pest. A person skilled in the art will find that the dose effective as a parasiticide may vary for the various compounds and compositions of the present invention, the desired effect and duration of the parasiticide, the target invertebrate pest species, the animal to be protected, the mode of application and similar, and the amount needed to achieve a particular result can be determined through simple experimentation.
[0183] For oral administration to homeothermic animals, the daily dosage of compound 1 of the present invention is typically in the range of about 0.01 mg / kg to about 100 mg / kg, more typically of about 0.5 mg / kg to about 100 mg / kg of animal body weight. For topical (e.g., dermal) administration, dips and sprays typically contain from about 0.5 ppm to about 5,000 ppm, more typically, from about 1 ppm to about 3,000 ppm, of compound 1 of the present invention.

权利要求:
Claims (6)
[1]
Claims
1. 4- [5- [3-chloro-5- (trifluoromethyl) phenyl] -4,5-dihydro-5- (trifluoromethyl) -3-isoxazolyl] -M- [2-oxo-2 CRYSTALLINE POLYMORPH - [(2,2,2trifluoroethyl) amino] ethyl] -1-naphthalenecarboxamide, characterized by a powder X-ray diffraction pattern having at least the 2θ reflection positions: 17,433; 18,586; 20.207; 20,791; 21.41; 22,112; 23,182; 24,567 and 27,844.
[2]
2. POLYMORPH, according to claim 1, characterized for being for use in the control of an invertebrate pest.
[3]
3. COMPOSITION, characterized by comprising the polymorph, as defined in claim 1, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition also optionally comprising at least one compound or agent additional biologically active.
4. COMPOSITION, in wake up with claim 3, characterized per be to protect one animal of a plague parasitic invertebrate. 5. COMPOSITION, in wake up with any one of
claims 3 to 4, characterized for being for oral administration.
[4]
6. METHOD FOR CONTROLING AN INVERTEBRATED PEST, characterized by comprising contacting the invertebrate pest or its environment with a biologically effective amount of the polymorph, as defined in claim 1, with the proviso that the method is not a method of treating the body human or animal therapy.
[5]
7. METHOD, according to claim 6, characterized by the environment being a plant.
[6]
8. USE OF THE POLYMORPH, as defined in claim 1, characterized by being to control an invertebrate pest in a plant.

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MD20120125A2|2013-05-31|

---

AU2011258621B2|2014-08-14|

---

HRP20160355T1|2016-05-06|

---

TN2012000557A1|2014-04-01|

---

RU2012157267A|2014-07-10|

---

ZA201208760B|2014-03-26|

---

SI2576523T1|2016-05-31|

---

KR20170015549A|2017-02-08|

---

PL2576523T3|2016-08-31|

---

JP2013528177A|2013-07-08|

---

ES2566402T3|2016-04-12|

---

RS54677B1|2016-08-31|

---

MD4363C1|2016-03-31|

---

JP5933530B2|2016-06-08|

---

MY156670A|2016-03-15|

---

US20130137735A1|2013-05-30|

---

KR20130124458A|2013-11-14|

---

AR117778A2|2021-08-25|

---

CA2799963C|2018-01-23|

---

MX2012013758A|2013-01-24|

---

BR112012030151A2|2015-10-20|

---

UY33397A|2011-12-01|

---

CA2799963A1|2011-12-01|

---

AU2011258621A1|2012-12-06|

---

EP2576523A1|2013-04-10|

---

CL2012003272A1|2013-08-02|

---

UA108881C2|2015-06-25|

---

NZ603584A|2015-02-27|

---

KR102060464B1|2019-12-30|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US1815604A|1922-10-31|1931-07-21|Winthrop Chem Co|Organic mercury compound|

---

US1679404A|1926-02-04|1928-08-07|Rockwood Sprinkler Co Massachusetts|Constant-alarm device for alarm valves|

---

BE403499A|1931-12-08|

---

US2891855A|1954-08-16|1959-06-23|Geigy Ag J R|Compositions and methods for influencing the growth of plants|

---

US3060084A|1961-06-09|1962-10-23|Du Pont|Improved homogeneous, readily dispersed, pesticidal concentrate|

---

US3235361A|1962-10-29|1966-02-15|Du Pont|Method for the control of undesirable vegetation|

---

US3299566A|1964-06-01|1967-01-24|Olin Mathieson|Water soluble film containing agricultural chemicals|

---

US3309192A|1964-12-02|1967-03-14|Du Pont|Method of controlling seedling weed grasses|

---

US4144050A|1969-02-05|1979-03-13|Hoechst Aktiengesellschaft|Micro granules for pesticides and process for their manufacture|

---

US3852416A|1971-05-27|1974-12-03|L Grubb|Tick and flea collar of solid solution plasticized vinylic resin-carbamate insecticide|

---

US3950360A|1972-06-08|1976-04-13|Sankyo Company Limited|Antibiotic substances|

---

US3984564A|1972-06-08|1976-10-05|Sankyo Company Limited|Antibiotic substances B-41, their production and their use as insecticides and acaricides|

---

US3920442A|1972-09-18|1975-11-18|Du Pont|Water-dispersible pesticide aggregates|

---

US3854216A|1973-05-14|1974-12-17|Owatonna Tool Co|Disc brake tool|

---

US3879532A|1974-01-18|1975-04-22|Shell Oil Co|Control by isoxazoles of endoparasitic nematodes|

---

SE434277B|1976-04-19|1984-07-16|Merck & Co Inc|SET TO MAKE NEW ANTIHELMINTICALLY EFFECTIVE ASSOCIATIONS BY CULTIVATING STREPTOMYCS AVERMITILIS|

---

US4172714A|1976-12-20|1979-10-30|E. I. Du Pont De Nemours And Company|Dry compactible, swellable herbicidal compositions and pellets produced therefrom|

---

US4129568A|1977-05-12|1978-12-12|Monsanto Company|2-[3-Aryl-2-isoxazolin-5-yl]benzoates|

---

US4199569A|1977-10-03|1980-04-22|Merck & Co., Inc.|Selective hydrogenation products of C-076 compounds and derivatives thereof|

---

ES488154A0|1979-02-05|1981-04-16|Schering Corp|A PROCEDURE FOR THE PREPARATION OF A COMPOUND D- (TREO-1-ARIL-2-ACILAMIDO-3-FLUOR-1-PROPANOL|

---

US4224901A|1979-04-16|1980-09-30|Carey Jr Sam H|Combination inner flea-tick collar and outer protective collar, for animals|

---

GB2095558B|1981-03-30|1984-10-24|Avon Packers Ltd|Formulation of agricultural chemicals|

---

US4820695A|1982-09-13|1989-04-11|Eli Lilly And Company|C-20-dihydro-deoxy--derivatives of macrolide antibiotics|

---

DE3246493A1|1982-12-16|1984-06-20|Bayer Ag, 5090 Leverkusen|METHOD FOR PRODUCING WATER-DISPERSIBLE GRANULES|

---

US5105009A|1983-06-02|1992-04-14|Zambon S.P.A.|Intermediates for the preparation of 1--1-hydroxy-2-amino-3-fluoropropane derivatives|

---

IT1173213B|1984-02-03|1987-06-18|Zambon Spa|PROCEDURE TO FLUORINE SOME DERIVATIVES FROM 1L-FENYL-2-AMINO-1,3-PROPANDIOL AND THEIR INTERMEDIATES|

---

US5332835A|1984-02-03|1994-07-26|Zambon S.P.A.|Process for fluorinating 1-phenyl-2-amino-1,3-propanediol compounds and new oxazoline compounds useful in this process|

---

US4582918A|1984-09-19|1986-04-15|Schering Corporation|Preparation of intermediates for -1-aryl-2-acylamido-3-fluoro-1-propanols|

---

US4973750A|1984-09-19|1990-11-27|Schering Corporation|Preparation of -1-aryl-2-acylamido-3-fluoro-1-propanols|

---

ES8800986A1|1985-07-27|1987-12-01|Pfizer|Antiparasitic avermectin and milbemycin derivatives and process for their preparation.|

---

US4916154A|1986-09-12|1990-04-10|American Cyanamid Company|23-Imino derivatives of LL-F28249 compounds|

---

US5180587A|1988-06-28|1993-01-19|E. I. Du Pont De Nemours And Company|Tablet formulations of pesticides|

---

US4876352A|1988-09-14|1989-10-24|Schering Corporation|Pressurized fluorination of hydroxy alkyl groups|

---

US5227494A|1988-09-14|1993-07-13|Schering Corporation|Process for preparing oxazoline compounds|

---

EP0415688B1|1989-08-30|1998-12-23|Aeci Ltd|Dosage device and use thereof|

---

EP0519937B1|1990-03-12|1994-12-28|E.I. Du Pont De Nemours And Company|Water-dispersible or water-soluble pesticide granules from heat-activated binders|

---

IL98599A|1990-06-28|1995-06-29|Merck & Co Inc|Stable salts of 4"-deoxy-4"-epi-methylamino avermectin b1a/b1b and insecticidal compositions containing them|

---

DE69122201T2|1990-10-11|1997-02-06|Sumitomo Chemical Co|Pesticides composition|

---

RU2071468C1|1990-10-25|1997-01-10|Шеринг Корпорейшн|Process for preparing [r-]-2,2-dichloro-n-1-2-hydroxy-2-[4-methylsulfonyl)-phenyl)ethylacetamide and process for preparing d-threo-2--4,5-phenyl)-4-oxazolemethanol|

---

US5184573A|1992-02-21|1993-02-09|Stevens Jr John L|Animal collar|

---

US5352832A|1992-12-18|1994-10-04|Schering Corporation|Asymmetric process for preparing florfenicol, thiamphenicol chloramphenicol and oxazoline intermediates|

---

US5399717A|1993-09-29|1995-03-21|Merck & Co., Inc.|Glycosidation route to 4"-epi-methylamino-4"-deoxyavermectin B1|

---

US5849736A|1993-11-24|1998-12-15|The Dupont Merck Pharmaceutical Company|Isoxazoline and isoxazole fibrinogen receptor antagonists|

---

GB9505651D0|1995-03-21|1995-05-10|Agrevo Uk Ltd|AgrEvo UK Limited|

---

US5555848A|1995-05-17|1996-09-17|Trujillo; Wendy J.|Pet/flea collar|

---

UA57738C2|1996-04-26|2003-07-15|Ніппон Сода Ко., Лтд|Derivatives of benzene substituted by heterocycles and herbicides|

---

AU726670B2|1996-06-06|2000-11-16|Dow Agrosciences Llc|Benzyloxy substituted aromatics and their use as fungicides and insecticides|

---

US5958888A|1996-07-02|1999-09-28|Merial, Inc.|Water miscible macrolide solutions|

---

US6239112B1|1998-07-09|2001-05-29|Merial, Inc.|Water miscible macrolide solutions|

---

US6271255B1|1996-07-05|2001-08-07|Biotica Technology Limited|Erythromycins and process for their preparation|

---

US5663361A|1996-08-19|1997-09-02|Schering Corporation|Process for preparing intermediates to florfenicol|

---

HRP980291A2|1997-06-16|1999-04-30|Lin-Hua Zhang|Crystalline roxifiban|

---

JP2003512290A|1997-09-10|2003-04-02|メルクエンドカムパニーインコーポレーテッド|8a-azalide as a livestock antibacterial agent|

---

US6339063B1|1997-09-10|2002-01-15|Merck & Co., Inc.|9a-azalides as veterinary antimicrobial agents|

---

AP9801420A0|1998-01-02|1998-12-31|Pfizer Prod Inc|Novel macrolides.|

---

CZ299375B6|1998-11-30|2008-07-09|Nihon Nohyaku Co., Ltd.|Phthalimide derivatives or salts thereof, agricultural- horticultural insecticidal agent and application method thereof|

---

CA2411293A1|1999-01-28|2000-07-28|Pfizer Products Inc.|Novel azalides and methods of making same|

---

GB2351081A|1999-06-18|2000-12-20|Lilly Forschung Gmbh|Pharmaceutically active imidazoline compounds and analogues thereof|

---

ES2199884T3|2000-01-27|2004-03-01|Pfizer Products Inc.|ANTIBIOTIC COMPOSITIONS OF AZALIDA.|

---

MY138097A|2000-03-22|2009-04-30|Du Pont|Insecticidal anthranilamides|

---

DE10114597A1|2001-03-23|2002-10-02|Bayer Cropscience Gmbh|Arylisoxazoline derivatives, process for their preparation and their use as pesticides|

---

RU2263117C2|2001-04-27|2005-10-27|Пфайзер Продактс Инк.|Method for preparing 4''-substituted derivatives of 9-deoxo-9a-aza-9a-homoerythromycin a|

---

TWI312274B|2001-08-13|2009-07-21|Du Pont|Method for controlling particular insect pests by applying anthranilamide compounds|

---

TWI283164B|2001-09-21|2007-07-01|Du Pont|Anthranilamide arthropodicide treatment|

---

CN1649829A|2002-03-08|2005-08-03|先灵-普劳有限公司|Novel florfenicol-type antibiotics|

---

BR0313943A|2002-08-26|2005-08-02|Nissan Chemical Ind Ltd|Substituted benzanilide compound and harmful organism control agent|

---

WO2004067528A1|2003-01-28|2004-08-12|E.I. Du Pont De Nemours And Company|Cyano anthranilamide insecticides|

---

DE10320782A1|2003-05-09|2004-11-25|Bayer Cropscience Ag|Substituted oxyarenes|

---

JP2005272452A|2004-02-23|2005-10-06|Nissan Chem Ind Ltd|Substituted benzanilide compound and pesticide|

---

EA014881B1|2004-03-05|2011-02-28|Ниссан Кемикал Индастриз, Лтд.|Substitited alkylbenzene derivatives|

---

JP2007530598A|2004-03-26|2007-11-01|サイトカイン・ファーマサイエンシズ・インコーポレーテッド|COMPOUND, COMPOSITION, MAKING PROCESS AND METHOD OF USE FOR INHIBITION OF MACROPHAGE MIGRATION INHIBITOR|

---

JP5051340B2|2005-06-06|2012-10-17|日産化学工業株式会社|Substituted isoxazoline compounds and pest control agents|

---

MY146795A|2005-06-09|2012-09-28|Novartis Ag|Process for the synthesis of organic compounds|

---

EP1932836B1|2005-09-02|2013-11-06|Nissan Chemical Industries, Ltd.|Isoxazoline-substituted benzamide compound and harmful organism-controlling agent|

---

JP2007106756A|2005-09-14|2007-04-26|Nissan Chem Ind Ltd|Substituted isoxazoline compound and pesticide|

---

KR20080080168A|2005-12-14|2008-09-02|이 아이 듀폰 디 네모아 앤드 캄파니|Isoxazolines for controlling invertebrate pests|

---

TW200803740A|2005-12-16|2008-01-16|Du Pont|5-aryl isoxazolines for controlling invertebrate pests|

---

WO2007074789A1|2005-12-26|2007-07-05|Nissan Chemical Industries, Ltd.|1,3-bis-3-hydroxypropan-1-one or 2-propen-1-one compound, and salt thereof|

---

TWI412322B|2005-12-30|2013-10-21|Du Pont|Isoxazolines for controlling invertebrate pests|

---

CN101400662B|2006-03-10|2012-11-14|日产化学工业株式会社|Substituted isoxazoline compound and pest control agent|

---

AU2007240954A1|2006-04-20|2007-11-01|E. I. Du Pont De Nemours And Company|Pyrazolines for controlling invertebrate pests|

---

JPWO2007125984A1|2006-04-28|2009-09-10|日本農薬株式会社|Isoxazoline derivatives, pest control agents and methods of use|

---

JP2008044880A|2006-08-15|2008-02-28|Bayer Cropscience Ag|Insecticidal isooxazolines|

---

US8119671B2|2007-03-07|2012-02-21|Nissan Chemical Industries, Ltd.|Isoxazoline-substituted benzamide compound and pest control agent|

---

US8372867B2|2007-04-10|2013-02-12|Bayer Cropscience Ag|Insecticidal aryl isoxazoline derivatives|

---

BRPI0809770B1|2007-06-13|2020-02-04|Du Pont|compost and composition to control an invertebrate pest|

---

TWI430995B|2007-06-26|2014-03-21|Du Pont|Naphthalene isoxazoline invertebrate pest control agents|

---

US8952175B2|2007-06-27|2015-02-10|Nissan Chemical Industries, Ltd.|Method for production of 3-hydroxypropan-1-one compound, method for production of 2-propen-1-one compound and method for production of isoxazoline compound|

---

SI2957284T1|2007-06-27|2018-04-30|E.I. Du Pont De Nemours And Company|Animal pest control method|

---

TWI556741B|2007-08-17|2016-11-11|英特威特國際股份有限公司|Isoxazoline compositions and their use as antiparasitics|

---

TWI600639B|2007-08-17|2017-10-01|杜邦股份有限公司|Compound for preparing 5-haloalkyl-4,5-dihydroisoxazole derivatives|

---

US8318757B2|2007-09-10|2012-11-27|Nissan Chemical Industries, Ltd.|Substituted isoxazoline compound and pest control agent|

---

US8367584B2|2007-10-03|2013-02-05|E.I. Du Pont De Nemours And Company|Naphthalene isoxazoline compounds for control of invertebrate pests|

---

TW201444787A|2008-04-09|2014-12-01|Du Pont|Method for preparing 3-trifluoromethyl chalcones|

---

CN104844531A|2008-07-09|2015-08-19|日产化学工业株式会社|Production method of isoxazoline-substituted benzoic acid amide compound|

---

AR076484A1|2009-04-28|2011-06-15|Basf Corp|COMPOSITIONS AND APPLICATORS OF PESTICIDES|TWI487486B|2009-12-01|2015-06-11|Syngenta Participations Ag|Insecticidal compounds based on isoxazoline derivatives|

---

EA038853B1|2011-09-12|2021-10-28|БЁРИНГЕР ИНГЕЛЬХАЙМ ЭНИМАЛ ХЕЛТ ЮЭсЭй ИНК.|Pesticidal compositions comprising an isoxazoline active agent and methods of use thereof|

---

UA119843C2|2012-02-06|2019-08-27|Меріал, Інк|Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof|

---

WO2014053401A2|2012-10-01|2014-04-10|Basf Se|Method of improving plant health|

---

US20150250175A1|2012-10-01|2015-09-10|Basf Se|Pesticidally active mixtures comprising anthranilamide compounds|

---

WO2014053407A1|2012-10-01|2014-04-10|Basf Se|N-thio-anthranilamide compounds and their use as pesticides|

---

WO2014053403A1|2012-10-01|2014-04-10|Basf Se|Method of controlling insecticide resistant insects|

---

JP2015530414A|2012-10-01|2015-10-15|ビーエーエスエフ ソシエタス・ヨーロピアＢａｓｆ Ｓｅ|Pesticide active mixture containing anthranilamido compound|

---

EP2903439A1|2012-10-01|2015-08-12|Basf Se|Method of controlling ryanodine-modulator insecticide resistant insects|

---

BR112015004074A2|2012-10-01|2017-07-04|Basf Se|method for controlling pests, use and seed of a cultivated plant.|

---

US9532946B2|2012-11-20|2017-01-03|Intervet Inc.|Manufacturing of semi-plastic pharmaceutical dosage units|

---

WO2014079820A1|2012-11-22|2014-05-30|Basf Se|Use of anthranilamide compounds for reducing insect-vectored viral infections|

---

MX2015007568A|2012-12-14|2015-10-14|Basf Se|Malononitrile compounds for controlling animal pests.|

---

US20150368236A1|2012-12-27|2015-12-24|Basf Se|2--5-hetaryl-thiazole compounds carrying an imine or imine-derived substituent for combating invertebrate pests|

---

NO2953942T3|2013-02-06|2018-03-24|

---

WO2014126208A1|2013-02-14|2014-08-21|日産化学工業株式会社|Crystalline polymorph of isoxazoline-substituted benzamide compound, and method for producing same|

---

CN111803465A|2013-03-15|2020-10-23|阿根塔创新有限公司|Chewable formulation|

---

ES2630373T3|2013-04-19|2017-08-21|Basf Se|N-substituted acyl-imino-pyridine compounds and derivatives to combat animal pests|

---

BR112015031439A2|2013-06-21|2017-07-25|Basf Se|methods for pest control or control, for the treatment, prevention and protection of soybean crops, for the control and protection of soybean propagating material, for the control or control of pests and the use of a compound of formula I|

---

PL3022185T3|2013-07-15|2018-02-28|Basf Se|Pesticide compounds|

---

UA117681C2|2013-09-19|2018-09-10|Басф Се|N-acylimino heterocyclic compounds|

---

WO2015055497A1|2013-10-16|2015-04-23|Basf Se|Substituted pesticidal pyrazole compounds|

---

CA2927784A1|2013-10-18|2015-04-23|Basf Agrochemical Products B.V.|Use of pesticidal active carboxamide derivative in soil and seed application and treatment methods|

---

CN106029645A|2013-12-18|2016-10-12|巴斯夫欧洲公司|N-substituted imino heterocyclic compounds|

---

CN105829296A|2013-12-18|2016-08-03|巴斯夫欧洲公司|Azole compounds carrying an imine-derived substituent|

---

KR20160104065A|2014-01-03|2016-09-02|바이엘 애니멀 헬스 게엠베하|Novel pyrazolyl-heteroarylamides as pesticides|

---

WO2015104422A1|2014-01-13|2015-07-16|Basf Se|Dihydrothiophene compounds for controlling invertebrate pests|

---

JP2017521441A|2014-07-15|2017-08-03|バイエル・アニマル・ヘルス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ａｎｉｍａｌ Ｈｅａｌｔｈ Ｇｍｂｈ|Aryl-triazolylpyridines as pest control agents|

---

UY36570A|2015-02-26|2016-10-31|Merial Inc|INJECTABLE FORMULATIONS OF PROLONGED ACTION THAT INCLUDE AN ISOXAZOLINE ACTIVE AGENT, METHODS AND USES OF THE SAME|

---

CN108055825B|2015-04-08|2021-03-30|勃林格殷格翰动物保健美国公司|Extended release injectable formulations comprising isoxazoline active agents, methods and uses thereof|

---

UY37137A|2016-02-24|2017-09-29|Merial Inc|ANTIPARASITARY COMPOUNDS OF ISOXAZOLINE, INJECTABLE FORMULATIONS OF PROLONGED ACTION THAT INCLUDE THEM, METHODS AND USES OF THE SAME|

---

WO2018039508A1|2016-08-25|2018-03-01|Merial, Inc.|Method for reducing unwanted effects in parasiticidal treatments|

---

CA3040278A1|2016-10-14|2018-04-19|Boehringer Ingelheim Animal Health USA Inc.|Pesticidal and parasiticidal vinyl isoxazoline compounds|

---

EA201992360A1|2017-04-05|2020-09-02|БЁРИНГЕР ИНГЕЛЬХАЙМ ЭНИМАЛ ХЕЛТ ЮЭсЭй ИНК.|CRYSTALLINE FORMS OF-AFOXOLANER|

---

AU2018318945A1|2017-08-14|2020-03-05|Boehringer Ingelheim Animal Health USA Inc.|Pesticidal and parasiticidal pyrazole-isoxazoline compounds|

---

RU2020117596A|2017-11-07|2021-12-08|Интервет Интернэшнл Б.В.|INJECTABLE ISOXAZOLINE PHARMACEUTICAL COMPOSITIONS AND THEIR APPLICATION|

---

AU2018363686A1|2017-11-07|2020-05-07|Intervet International B.V.|Process for preparing large size isoxazoline particles|

---

WO2021242481A1|2020-05-28|2021-12-02|Boehringer Ingelheim Animal Health USA Inc.|Bi-modal release intra-ruminal capsule device and methods of use thereof|

---

WO2021254445A1|2020-06-19|2021-12-23|东莞市东阳光仿制药研发有限公司|Crystal form of gaba inhibitor and preparation method therefor|

法律状态:
2015-12-08| B08F| Application fees: application dismissed [chapter 8.6 patent gazette]|Free format text: REFERENTE A 3A ANUIDADE. |

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2016-03-08| B08G| Application fees: restoration [chapter 8.7 patent gazette]|

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2017-11-28| B25G| Requested change of headquarter approved|Owner name: E.I. DU PONT DE NEMOURS AND COMPANY (US) |

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2018-04-10| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

---

2018-05-08| B06I| Publication of requirement cancelled [chapter 6.9 patent gazette]|

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2019-01-15| B06T| Formal requirements before examination [chapter 6.20 patent gazette]|

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2019-05-14| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|

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2019-09-10| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2019-10-08| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 19/05/2011, OBSERVADAS AS CONDICOES LEGAIS. (CO) 20 (VINTE) ANOS CONTADOS A PARTIR DE 19/05/2011, OBSERVADAS AS CONDICOES LEGAIS |

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2019-12-10| B16C| Correction of notification of the grant|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 19/05/2011, OBSERVADAS AS CONDICOES LEGAIS. (CO) REFERENTE A RPI 2544 DE 08/10/2019,QUANTO AO ITEM (71) ENDERECO DO DEPOSITANTE. |

优先权:

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申请号 | 申请日 | 专利标题

---

US34895810P| true| 2010-05-27|2010-05-27|

---

US61/348,958|2010-05-27|

---

PCT/US2011/037083|WO2011149749A1|2010-05-27|2011-05-19|Crystalline form of 4- [5 - [3 -chloro-5 -phenyl] -4, 5 - dihydro - 5 --3 - isoxazolyl] -n- [2-0x0-2- [amino] ethyl] -1- naphthalenecarboxamide|

---