TW202300019A - Bicyclic amides for controlling invertebrate pests - Google Patents
Bicyclic amides for controlling invertebrate pests Download PDFInfo
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
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- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/002—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits
- A01N25/006—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits insecticidal
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/12—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings condensed with a carbocyclic ring
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
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- A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
- A01N55/08—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing boron
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- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
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- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
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- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
Description
本揭露關於適用於農學和非農學用途的某些二環醯胺、其 N-氧化物、鹽和組成物，以及它們用於在農學和非農學環境中防治無脊椎害蟲諸如節肢動物之方法。 The present disclosure pertains to certain dicyclamides, N -oxides, salts and compositions thereof suitable for agronomic and non-agronomic use, and their use in methods of controlling invertebrate pests such as arthropods in agronomic and non-agronomic settings.
防治無脊椎害蟲在實現高作物效率中是極其重要的。無脊椎害蟲對生長中和儲存的農作物的損害可導致生產力顯著降低，並由此導致消費者的成本增加。對林業、溫室作物、觀賞植物、苗圃作物、儲存食品和纖維產品、家畜、家庭、草皮、木材產品以及公共健康和動物健康中的無脊椎害蟲的防治也是重要的。為了該等目的，許多產品係可商購的，但持續需要更有效、較低成本、較低毒性、對環境更安全或具有不同的作用位點的新型化合物。Control of invertebrate pests is extremely important in achieving high crop efficiency. Damage to growing and stored crops by invertebrate pests can lead to significant reductions in productivity and thus increased costs to consumers. Also important is the control of invertebrate pests in forestry, greenhouse crops, ornamental plants, nursery crops, stored food and fiber products, livestock, household, turf, wood products, and public and animal health. Many products are commercially available for these purposes, but there is a continuing need for new compounds that are more effective, lower cost, less toxic, safer for the environment or have a different site of action.
本揭露關於式
1的化合物（包括所有立體異構物）、其
N-氧化物和鹽，含有它們的組成物，以及它們用於防治無脊椎害蟲的用途：
本揭露還提供了一種組成物，該組成物包含式 1的化合物、其 N-氧化物或鹽以及選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的至少一種附加組分。在一個實施方式中，本揭露還提供了一種用於防治無脊椎害蟲的組成物，該組成物包含式 1的化合物、其 N-氧化物或鹽以及至少一種選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的附加組分，所述組成物視需要進一步包含至少一種附加生物學活性化合物或藥劑。 The present disclosure also provides a composition comprising a compound of formula 1 , an N -oxide or a salt thereof and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. In one embodiment, the present disclosure also provides a composition for controlling invertebrate pests, the composition comprising the compound of formula 1 , its N -oxide or salt and at least one selected from surfactants, solid diluents An additional component of the group consisting of a liquid diluent, said composition optionally further comprising at least one additional biologically active compound or agent.
本揭露還提供了一種用於防治無脊椎害蟲之方法，該方法包括使無脊椎害蟲或其環境與生物學有效量的式 1的化合物、其 N-氧化物或鹽（例如，作為本文所述之組成物）接觸。本揭露還關於這樣之方法，其中無脊椎害蟲或其環境與包含生物學有效量的式 1的化合物、其 N-氧化物或鹽以及至少一種選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的附加組分的組成物接觸，所述組成物視需要進一步包含生物學有效量的至少一種附加生物學活性化合物或藥劑。 The disclosure also provides a method for controlling invertebrate pests, the method comprising administering to the invertebrate pests or an environmentally and biologically effective amount of a compound of formula 1 , an N -oxide or a salt thereof (for example, as described herein composition) contact. The present disclosure also relates to a method wherein the invertebrate pest or its environment is mixed with a biologically effective amount of a compound of formula 1 , its N -oxide or salt and at least one selected from the group consisting of surfactants, solid diluents and liquid diluents. The composition of the additional components of the group of constituents is contacted, the composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent.
本揭露還提供了一種用於防治無脊椎害蟲之方法，該方法包括使無脊椎害蟲或其環境與生物學有效量的上述組成物中的任一種接觸，其中該環境係植株。The present disclosure also provides a method for controlling an invertebrate pest, the method comprising contacting the invertebrate pest or its environment with a biologically effective amount of any of the above compositions, wherein the environment is a plant.
本揭露還提供了一種用於防治無脊椎害蟲之方法，該方法包括使無脊椎害蟲或其環境與生物學有效量的上述組成物中的任一種接觸，其中該環境係動物。The present disclosure also provides a method for controlling an invertebrate pest, the method comprising contacting the invertebrate pest or its environment with a biologically effective amount of any of the above compositions, wherein the environment is an animal.
本揭露還提供了一種用於防治無脊椎害蟲之方法，該方法包括使無脊椎害蟲或其環境與生物學有效量的上述組成物中的任一種接觸，其中該環境係種子。The present disclosure also provides a method for controlling an invertebrate pest, the method comprising contacting the invertebrate pest or its environment with a biologically effective amount of any of the above compositions, wherein the environment is a seed.
本揭露還提供了一種用於保護種子免受無脊椎害蟲侵害之方法，該方法包括使種子與生物學有效量的式 1的化合物、其 N-氧化物或鹽（例如，作為本文所述之組成物）接觸。本揭露還關於經處理的種子（即與式 1的化合物接觸的種子）。 The disclosure also provides a method for protecting seeds from invertebrate pests, the method comprising treating the seeds with a biologically effective amount of a compound of formula 1 , an N -oxide or a salt thereof (for example, as described herein composition) contact. The present disclosure also relates to treated seeds (ie, seeds contacted with compounds of formula 1 ).
本揭露還提供了一種用於增加作物植株的活力（vigor）之方法，該方法包括使作物植株、生長出作物植株的種子或作物植株的所在地（例如，生長介質）與生物學有效量的式 1的化合物（例如，作為本文所述之組成物）接觸。 The present disclosure also provides a method for increasing the vigor of a crop plant, the method comprising combining a crop plant, a seed from which a crop plant grows, or a locus (for example, a growth medium) of a crop plant with a biologically effective amount of the formula 1 (eg, as a composition described herein).
本揭露進一步提供了一種用於保護動物免受無脊椎寄生性害蟲侵害之方法，該方法包括向動物施用殺寄生蟲有效量的式 1的化合物、其 N-氧化物或鹽（例如，作為本文所述之組成物）。本揭露還提供了式 1的化合物、其 N-氧化物或鹽（例如，作為本文所述之組成物）在保護動物免受無脊椎害蟲侵害中的用途。 The present disclosure further provides a method for protecting an animal from an invertebrate parasitic pest, the method comprising administering to the animal a parasiticidally effective amount of a compound of Formula 1 , an N -oxide or a salt thereof (for example, as described herein the composition described). The present disclosure also provides the use of a compound of Formula 1 , an N -oxide or a salt thereof (eg, as a composition described herein) for protecting an animal from an invertebrate pest.
如本文所使用的，術語「包含（comprises）」、「包含（comprising）」、「包括（includes）」、「包括（including）」、「具有（has）」、「具有（having）」、「含有（contains）」、「含有（containing）」、「特徵為（characterized by）」或其任何其他變體，旨在涵蓋非排他性包括，受到另外明確指出的任何限制。例如，包含一系列元素的組成物、混合物、製程或方法不必僅限於那些元素，而是可以包括未明確列出的其他元素，或此類組成物、混合物、製程或方法的其他固有元素。As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", " "contains", "containing", "characterized by" or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitations otherwise expressly indicated. For example, a composition, mixture, process, or method comprising a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed, or otherwise inherent to such composition, mixture, process, or method.
連接短語「由……組成」排除任何未指出的元素、步驟或成分。如果在請求項中，則此類短語將使請求項為封閉式，使其不包含除那些敘述的材料以外的材料，但與其相關的常規雜質除外。當短語「由……組成」出現在請求項主體的從屬項中而非緊接前序部分時，該短語僅僅限制該從屬項中闡述的元素；其他元素不從整個請求項中被排除。The linking phrase "consisting of" excludes any unspecified element, step or ingredient. If in a claim, such phrases will make the claim closed so that it contains no material other than those recited, except for the usual impurities associated therewith. When the phrase "consisting of" appears in a dependent item of the claim body rather than immediately preceding the preamble, the phrase restricts only the elements set forth in the dependent item; other elements are not excluded from the overall claim .
連接短語「基本上由...組成」用於限定除了字面揭露的那些以外還包括材料、步驟、特徵、組分、或元素的組成物或方法，前提係該等附加的材料、步驟、特徵、組分、或元素不會實質影響請求保護的揭露的基本和新穎特徵。術語「基本上由……組成」居於「包含」和「由……組成」中間。The conjunction phrase "consisting essentially of" is used to define a composition or method that includes materials, steps, features, components, or elements in addition to those literally disclosed, provided that such additional materials, steps, The features, components, or elements do not materially affect the basic and novel characteristics of the claimed disclosure. The term "consisting essentially of" is intermediate between "comprising" and "consisting of".
當申請人已經用開放式術語如「包含（comprising）」定義了實施方式或其一部分時，則應易於理解（除非另外說明），說明書應被解釋為還使用術語「基本上由……組成」或「由……組成」描述該實施方式。When the applicant has defined an embodiment or a part thereof using an open-ended term such as "comprising", it should be readily understood that (unless otherwise specified) the description should be interpreted as also using the term "consisting essentially of" or "consisting of" describes the embodiment.
此外，除非有相反的明確說明，否則「或」係指包含性的「或」，而不是指排他性的「或」。例如，條件A或者B藉由以下中的任一項滿足：A為真（或存在）且B為假（或不存在），A為假（或不存在）且B為真（或存在），以及A和B都為真（或存在）。Furthermore, unless expressly stated to the contrary, "or" means an inclusive "or", not an exclusive "or". For example, condition A or B is satisfied by any of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).
同樣，在本揭露之元素或組分前的不定冠詞「一個/一種（a/an）」關於元素或組分的例子（即，出現）的數量旨在係非限制性的。因此，「一個/一種（a或an）」應理解為包括一個/一種或至少一個/一種，並且元素或組分的單數詞語形式還包括複數，除非該數字明顯意指單數。Likewise, the indefinite article "a/an" preceding an element or component of the present disclosure is intended to be non-limiting with respect to the number of instances (ie, occurrences) of the element or component. Thus, "a or an" should be read to include one or at least one, and singular word forms of elements or components also include plural unless the number is clearly meant to be singular.
如在本揭露中所提及，術語「無脊椎害蟲」包括作為害蟲具有經濟重要性的節肢動物、腹足動物、線蟲和蠕蟲。術語「節肢動物」包括昆蟲、蟎蟲、蜘蛛、蠍子、蜈蚣、千足蟲、鼠婦（pill bug）和綜合蟲（symphylan）。術語「腹足動物」包括蝸牛、蛞蝓和其他柄眼目（Stylommatophora）。術語「線蟲」包括線蟲動物門（Nematoda）成員，諸如植食性線蟲和寄生於動物的蠕蟲線蟲。術語「蠕蟲」包括所有寄生蟲，諸如蛔蟲（線蟲動物門）、心絲蟲（線蟲動物門，胞管腎綱（Secernentea））、吸蟲（fluke）（扁形動物門（Platyhelminthes），吸蟲綱（Tematoda））、棘頭蟲（棘頭動物門（Acanthocephala））和絛蟲（扁形動物門，絛蟲綱（Cestoda））。As referred to in this disclosure, the term "invertebrate pest" includes arthropods, gastropods, nematodes and helminths of economic importance as pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. The term "gastropod" includes snails, slugs and other members of the order Stylommatophora. The term "nematode" includes members of the phylum Nematoda, such as herbivorous nematodes and helminth nematodes that parasitize animals. The term "worm" includes all parasites such as roundworms (phylum Nematodes), heartworms (phylum Nematodes, class Secernentea), flukes (phylum Platyhelminthes, class Trematodes Tematoda), acanthocephala (Acanthocephala) and tapeworms (Platyhelminthes, class Cestoda).
在本揭露之上下文中，「無脊椎害蟲防治」意指抑制無脊椎害蟲的發育（包括死亡率、取食減少和/或交配干擾），並且相關的表述類似地定義。In the context of this disclosure, "invertebrate pest control" means inhibiting the development of invertebrate pests (including mortality, reduced feeding and/or mating disturbance), and related expressions are defined similarly.
術語「農學」係指生產大田作物，諸如用於食物和纖維，並且包括玉蜀黍（maize）或玉米、大豆和其他豆類、稻、穀物（例如，小麥、燕麥、大麥、黑麥和稻）、葉類蔬菜（例如，生菜、捲心菜和其他油菜作物）、果實類蔬菜（例如，番茄、胡椒、茄子、十字花科植物和瓜類作物（cucurbit））、土豆、甘薯、葡萄、棉花、樹果（例如，仁果類（pome）、核果類（stone）和柑橘類）、小果（例如，漿果和櫻桃）和其他特種作物（specialty crop）（例如，低芥酸菜籽（canola）、向日葵和橄欖）的生長。The term "agronomy" refers to the production of field crops, such as for food and fiber, and includes maize or corn, soybeans and other legumes, rice, cereals (e.g., wheat, oats, barley, rye, and rice), leaf vegetables (e.g., lettuce, cabbage, and other rapeseed crops), fruit vegetables (e.g., tomato, pepper, eggplant, cruciferous, and cucurbit), potatoes, sweet potatoes, grapes, cotton, tree fruits ( such as pome, stone, and citrus), small fruits (e.g., berries and cherries), and other specialty crops (e.g., canola, sunflower, and olive ) growth.
術語「非農學」係指不同於大田作物，諸如園藝作物（例如，溫室、苗圃或不在大田生長的觀賞植物）、住宅、農業、商業和工業結構、草皮（例如，草場（sod farm）、牧場、高爾夫球場、草坪、運動場等）、木材產品、儲存產品、農林業和植被管理、公共健康（即人類）和動物健康（例如，家養動物諸如寵物、家畜和家禽，非家養動物諸如野生動物）應用。The term "nonagronomic" refers to crops other than field crops, such as horticultural crops (e.g., greenhouse, nursery, or ornamental plants not grown in field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture , golf courses, lawns, sports fields, etc.), wood products, stored products, agroforestry and vegetation management, public health (i.e., humans) and animal health (e.g., domesticated animals such as pets, livestock and poultry, non-domesticated animals such as wild animals) application.
術語「作物活力」係指作物植株的生長速率或生物量積累。「活力的增加」係指作物植株相對於未經處理的對照作物植株在生長或生物量積累上的增加。術語「作物產量」係指收穫作物植株後獲得的作物材料在數量和品質上的回報。「作物產量的增加」係指相對於未經處理的對照作物植株的作物產量增加。The term "crop vigor" refers to the growth rate or biomass accumulation of crop plants. "Increase in vigor" means an increase in growth or biomass accumulation of a crop plant relative to an untreated control crop plant. The term "crop yield" refers to the return in quantity and quality of crop material obtained after harvesting of crop plants. "Increase in crop yield" means an increase in crop yield relative to untreated control crop plants.
術語「生物學有效量」係指當施加於（即接觸）待防治的無脊椎害蟲或其環境，或植株、生長出該植株的種子或該植株的所在地（例如，生長介質）以保護植株免受無脊椎害蟲的傷害或為了其他期望的效果（例如，增加植株活力）時，足以產生所期望的生物效應的生物學活性化合物（例如，式 1的化合物）的量。 The term "biologically effective amount" means when applied to (i.e. contacted with) the invertebrate pest to be controlled or its environment, or the plant, the seed from which the plant is grown, or the locus of the plant (e.g., the growth medium) to protect the plant from Amount of a biologically active compound (eg, a compound of formula 1 ) sufficient to produce the desired biological effect upon injury by an invertebrate pest or for other desired effects (eg, increased plant vigor).
非農學應用包括藉由向待保護動物施用殺寄生蟲有效（即生物學有效）量的本揭露化合物（典型地呈被配製用於獸醫用途的組成物的形式）來保護動物免受無脊椎寄生性害蟲的侵害。如在本揭露和請求項中所提及，術語「殺寄生蟲的（parasiticidal）」和「殺寄生蟲地（parasiticidally）」係指對無脊椎寄生性害蟲的可觀察影響，以保護動物免受害蟲的侵害。殺寄生蟲效果典型地與減少目標無脊椎寄生性害蟲的出現或活動有關。此類對害蟲的影響包括壞死、死亡、生長遲緩、移動性降低或留在宿主動物身上或體內的能力降低、取食減少和生殖抑制。該等對無脊椎寄生性害蟲的影響防治（包括預防、減少或消除）動物的寄生蟲侵害或感染。Non-agronomic applications include the protection of animals against invertebrate parasitism by administering to the animal to be protected a parasiticidally effective (i.e., biologically effective) amount of a compound of the disclosure, typically in the form of a composition formulated for veterinary use. Infestation by sexual pests. As referred to in this disclosure and claims, the terms "parasiticidal" and "parasiticidally" refer to an observable effect on an invertebrate parasitic pest to protect animals from Infestation by pests. Parasiticidal effects are typically associated with reducing the presence or activity of target invertebrate parasitic pests. Such effects on the pest include necrosis, death, growth retardation, reduced mobility or ability to remain on or in the host animal, reduced feeding and reproductive inhibition. Such Effects on Invertebrate Parasitic Pests Control (including prevention, reduction or elimination) of parasitic infestation or infection in animals.
結構片段中的波浪線表示片段與分子其餘部分的附接點。例如，當表1所示結構中的變數T定義為T-2時，平分2-氧雜二環[3.1.0]己烷T-2的6位上的鍵的波浪線意指2-氧雜二環[3.1.0]己烷T-2在所述6位處附接到表1結構的其餘部分，如下所示。
在以上詳述中，術語「烷基」，單獨使用或在複合詞諸如「烷硫基」或「鹵代烷基」中使用，包括直鏈或支鏈烷基，諸如甲基、乙基、正丙基、異丙基、或不同的丁基、戊基、或己基異構物。「烯基」包括直鏈或支鏈的烯烴，諸如乙烯基、1-丙烯基、2-丙烯基，以及不同的丁烯基、戊烯基和己烯基異構物。「烯基」還包括聚烯，如1,2-丙二烯基和2,4-己二烯基。「炔基」包括直鏈或支鏈的炔烴，諸如乙炔基、1-丙炔基、2-丙炔基，以及不同的丁炔基、戊炔基和己炔基異構物。「炔基」還可包括由多個三鍵構成的部分，諸如2,5-己二炔基。In the above detailed description, the term "alkyl", used alone or in compound words such as "alkylthio" or "haloalkyl", includes straight or branched chain alkyl groups such as methyl, ethyl, n-propyl , isopropyl, or different butyl, pentyl, or hexyl isomers. "Alkenyl" includes straight or branched chain alkenes such as vinyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl, and hexenyl isomers. "Alkenyl" also includes polyalkenes such as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight or branched chain alkynes such as ethynyl, 1-propynyl, 2-propynyl, and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" may also include moieties composed of multiple triple bonds, such as 2,5-hexadiynyl.
「烷氧基」包括例如甲氧基、乙氧基、正丙氧基、異丙氧基和不同的丁氧基、戊氧基和己氧基異構物。「烷氧基烷基」表示烷基上的烷氧基取代。「烷氧基烷基」的實例包括CH 3OCH 2、CH 3OCH 2CH 2、CH 3CH 2OCH 2、CH 3CH 2CH 2CH 2OCH 2和CH 3CH 2OCH 2CH 2。「烷氧基烷氧基」表示另一烷氧基部分上的烷氧基取代。「烷氧基烷氧基」的實例包括CH 3OCH 2O、CH 3OCH 2CH 2O、CH 3CH 2OCH 2O、CH 3CH 2CH 2OCH 2O和CH 3CH 2OCH 2CH 2O。「烷氧基烷氧基烷基」表示烷基上的烷氧基烷氧基取代。「烷氧基烷氧基烷基」的實例包括CH 3OCH 2OCH 2、CH 3OCH 2OCH 2CH 2和CH 3CH 2OCH 2OCH 2。 "Alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy and the different butoxy, pentyloxy and hexyloxy isomers. "Alkoxyalkyl" means an alkoxy substitution on an alkyl group. Examples of "alkoxyalkyl" include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 . "Alkoxyalkoxy" means an alkoxy substitution on another alkoxy moiety. Examples of "alkoxyalkoxy" include CH 3 OCH 2 O, CH 3 OCH 2 CH 2 O, CH 3 CH 2 OCH 2 O, CH 3 CH 2 CH 2 OCH 2 O and CH 3 CH 2 OCH 2 CH 2 O. "Alkoxyalkoxyalkyl" means an alkoxyalkoxy substitution on an alkyl group. Examples of "alkoxyalkoxyalkyl" include CH 3 OCH 2 OCH 2 , CH 3 OCH 2 OCH 2 CH 2 and CH 3 CH 2 OCH 2 OCH 2 .
「烷硫基」包括支鏈或直鏈的烷硫基部分，諸如甲硫基、乙硫基，以及不同的丙硫基、丁硫基、戊硫基和己硫基異構物。「烷基亞磺醯基」包括烷基亞磺醯基基團的兩種鏡像異構物。「烷基亞磺醯基」的實例包括CH 3S(O)-、CH 3CH 2S(O)-、CH 3CH 2CH 2S(O)-、(CH 3) 2CHS(O)-以及不同的丁基亞磺醯基、戊基亞磺醯基和己基亞磺醯基異構物。「烷基磺醯基」的實例包括CH 3S(O) 2-、CH 3CH 2S(O) 2-、CH 3CH 2CH 2S(O) 2-、(CH 3) 2CHS(O) 2-以及不同的丁基磺醯基、戊基磺醯基和己基磺醯基異構物。「烷硫基烷基」表示烷基上的烷硫基取代。「烷硫基烷基」的實例包括CH 3SCH 2、CH 3SCH 2CH 2、CH 3CH 2SCH 2、CH 3CH 2CH 2SCH 2和CH 3CH 2SCH 2CH 2；「烷基亞磺醯基烷基」和「烷基磺醯基烷基」分別包括相應的亞碸和碸。 "Alkylthio" includes branched or straight chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylsulfinyl" includes both mirror-image isomers of an alkylsulfinyl group. Examples of "alkylsulfinyl" include CH 3 S(O)-, CH 3 CH 2 S(O)-, CH 3 CH 2 CH 2 S(O)-, (CH 3 ) 2 CHS(O) - and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH 3 S(O) 2 -, CH 3 CH 2 S(O) 2 -, CH 3 CH 2 CH 2 S(O) 2 -, (CH 3 ) 2 CHS ( O) 2 - and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Alkylthioalkyl" means an alkylthio substitution on an alkyl group. Examples of "alkylthioalkyl" include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 ; "Sulfinylalkyl" and "alkylsulfonylalkyl" include the corresponding sulfene and sulfene, respectively.
「烷基胺基」包括被直鏈或支鏈烷基基團取代的NH基團。「烷基胺基」的實例包括CH 3CH 2NH、CH 3CH 2CH 2NH和(CH 3) 2CHCH 2NH。「二烷基胺基」的實例包括(CH 3) 2N、(CH 3CH 2CH 2) 2N和CH 3CH 2(CH 3)N。「烷基胺基烷基」表示烷基上的烷基胺基取代。「烷基胺基烷基」的實例包括CH 3NHCH 2、CH 3NHCH 2CH 2、CH 3CH 2NHCH 2、CH 3CH 2CH 2CH 2NHCH 2和CH 3CH 2NHCH 2CH 2。「二烷基胺基烷基」的實例包括(CH 3) 2NCH 2、(CH 3CH 2CH 2) 2NCH 2CH 2和CH 3CH 2(CH 3)NCH 2。 "Alkylamino" includes NH groups substituted with straight or branched chain alkyl groups. Examples of "alkylamino" include CH 3 CH 2 NH, CH 3 CH 2 CH 2 NH and (CH 3 ) 2 CHCH 2 NH. Examples of "dialkylamino" include (CH 3 ) 2 N, (CH 3 CH 2 CH 2 ) 2 N and CH 3 CH 2 (CH 3 )N. "Alkylaminoalkyl" means alkylamino substitution on an alkyl group. Examples of "alkylaminoalkyl" include CH 3 NHCH 2 , CH 3 NHCH 2 CH 2 , CH 3 CH 2 NHCH 2 , CH 3 CH 2 CH 2 CH 2 NHCH 2 and CH 3 CH 2 NHCH 2 CH 2 . Examples of "dialkylaminoalkyl" include (CH 3 ) 2 NCH 2 , (CH 3 CH 2 CH 2 ) 2 NCH 2 CH 2 and CH 3 CH 2 (CH 3 )NCH 2 .
「烷基羰基」表示鍵合到C(=O)部分上的直鏈或支鏈烷基基團。「烷基羰基」的實例包括CH 3C(=O)、CH 3CH 2CH 2C(=O)和(CH 3) 2CHC(=O)。「烷氧基羰基」的實例包括CH 3OC(=O)、CH 3CH 2OC(=O)、CH 3CH 2CH 2OC(=O)、(CH 3) 2CHOC(=O)以及不同的丁氧基羰基和戊氧基羰基異構物。「烷基胺基羰基」的實例包括CH 3NHC(=O)、CH 3CH 2NHC(=O)、CH 3CH 2CH 2NHC(=O)、(CH 3) 2CHNHC(=O)以及不同的丁基胺基羰基、戊基胺基羰基和己基胺基羰基異構物。「二烷基胺基羰基」的實例包括(CH 3) 2NC(=O)、(CH 3CH 2) 2NC(=O)、CH 3CH 2(CH 3)NC(=O)、(CH 3) 2CH(CH 3)NC(=O)和CH 3CH 2CH 2(CH 3)NC(=O)。 "Alkylcarbonyl" means a straight or branched chain alkyl group bonded to a C(=0) moiety. Examples of "alkylcarbonyl" include CH 3 C(=O), CH 3 CH 2 CH 2 C(=O), and (CH 3 ) 2 CHC(=O). Examples of "alkoxycarbonyl" include CH 3 OC(=O), CH 3 CH 2 OC(=O), CH 3 CH 2 CH 2 OC(=O), (CH 3 ) 2 CHOC(=O) and Different butoxycarbonyl and pentyloxycarbonyl isomers. Examples of "alkylaminocarbonyl" include CH 3 NHC(=O), CH 3 CH 2 NHC(=O), CH 3 CH 2 CH 2 NHC( = O), (CH 3 ) 2 CHNHC(=O) and the different butylaminocarbonyl, pentylaminocarbonyl, and hexylaminocarbonyl isomers. Examples of "dialkylaminocarbonyl" include (CH 3 ) 2 NC(=O), (CH 3 CH 2 ) 2 NC(=O), CH 3 CH 2 (CH 3 )NC(=O), ( CH 3 ) 2 CH(CH 3 )NC(=0) and CH 3 CH 2 CH 2 (CH 3 )NC(=0).
術語「烷氧基羰基烷基」表示烷基上的烷氧基羰基取代。「烷氧基羰基烷基」的實例包括CH 3CH 2OC(=O)CH 2、(CH 3) 2CHOC(=O)CH 2和CH 3OC(=O)CH 2CH 2。術語「烷基羰基胺基」表示鍵合到C(=O)NH部分的烷基。「烷基羰基胺基」的實例包括CH 3CH 2C(=O)NH和CH 3CH 2CH 2C(=O)NH。術語「烷氧基羰基胺基」表示鍵合到C(=O)NH部分的烷氧基。「烷氧基羰基胺基」的實例包括CH 3OC(=O)NH和CH 3CH 2OC(=O)NH。 The term "alkoxycarbonylalkyl" denotes an alkoxycarbonyl substitution on an alkyl group. Examples of "alkoxycarbonylalkyl" include CH 3 CH 2 OC(=O)CH 2 , (CH 3 ) 2 CHOC(=O)CH 2 and CH 3 OC(=O)CH 2 CH 2 . The term "alkylcarbonylamino" denotes an alkyl group bonded to a C(=O)NH moiety. Examples of "alkylcarbonylamino" include CH 3 CH 2 C(=O)NH and CH 3 CH 2 CH 2 C(=O)NH. The term "alkoxycarbonylamino" denotes an alkoxy group bonded to a C(=O)NH moiety. Examples of "alkoxycarbonylamino" include CH 3 OC(=O)NH and CH 3 CH 2 OC(=O)NH.
術語「烷基胺基羰基烷基」表示附接到烷基的直鏈或支鏈烷基胺基羰基。「烷基胺基羰基烷基」的實例包括(CH 3) 2CHCH 2NHC(=O)CH 2和CH 3CH 2NHC(=O)CH 2。「二烷基胺基羰基烷基」的實例包括CH 3CH 2CH 2(CH 3)NC(=O)CH 2和(CH 3) 2NC(=O)CH 2。 The term "alkylaminocarbonylalkyl" denotes a straight or branched chain alkylaminocarbonyl group attached to an alkyl group. Examples of "alkylaminocarbonylalkyl" include (CH 3 ) 2 CHCH 2 NHC(=O)CH 2 and CH 3 CH 2 NHC(=O)CH 2 . Examples of "dialkylaminocarbonylalkyl" include CH 3 CH 2 CH 2 (CH 3 )NC(=O)CH 2 and (CH 3 ) 2 NC(=O)CH 2 .
「環烷基」包括例如環丙基、環丁基、環戊基、環己基、環庚基和環辛基。術語「環烷基烷基」表示烷基部分上的環烷基取代。「環烷基烷基」的實例包括環丙基甲基、環戊基乙基，以及其他鍵合到直鏈或支鏈烷基基團上的環烷基部分。術語「烷基環烷基」表示環烷基部分上的烷基取代，並且包括例如乙基環丙基、異丙基環丁基、甲基環戊基和甲基環己基。「烷基環烷基烷基」表示被烷基環烷基取代的烷基基團。「烷基環烷基烷基」的實例包括甲基環己基甲基和乙基環丙基甲基。「環烯基」包括諸如環戊烯基和環己烯基的基團以及具有多於一個雙鍵的基團，諸如1,3-環己二烯基或1,4-環己二烯基。術語「環烷基環烷基」表示另一環烷基環上的環烷基取代，其中每個環烷基環獨立地具有從3至7個碳原子環成員。環烷基環烷基的實例包括環丙基環丙基（諸如1,1'-二環丙基-1-基、1,1'-二環丙基-2-基）、環己基環戊基（諸如4-環戊基環己基）和環己基環己基（諸如1,1'-二環己基-1-基）以及不同的順式和反式環烷基環烷基異構物（諸如(1 R,2 S)-1,1'-二環丙基-2-基和(1 R,2 R)-1,1'-二環丙基-2-基）。 "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight or branched chain alkyl groups. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, isopropylcyclobutyl, methylcyclopentyl and methylcyclohexyl. "Alkylcycloalkylalkyl" means an alkyl group substituted with an alkylcycloalkyl. Examples of "alkylcycloalkylalkyl" include methylcyclohexylmethyl and ethylcyclopropylmethyl. "Cycloalkenyl" includes groups such as cyclopentenyl and cyclohexenyl as well as groups having more than one double bond such as 1,3-cyclohexadienyl or 1,4-cyclohexadienyl . The term "cycloalkylcycloalkyl" denotes a cycloalkyl substitution on another cycloalkyl ring, wherein each cycloalkyl ring independently has from 3 to 7 carbon atom ring members. Examples of cycloalkylcycloalkyl groups include cyclopropylcyclopropyl (such as 1,1'-dicyclopropyl-1-yl, 1,1'-dicyclopropyl-2-yl), cyclohexylcyclopentyl (such as 4-cyclopentylcyclohexyl) and cyclohexylcyclohexyl (such as 1,1'-dicyclohexyl-1-yl) and different cis and trans cycloalkylcycloalkyl isomers (such as (1 R ,2 S )-1,1'-dicyclopropyl-2-yl and (1 R ,2 R )-1,1'-dicyclopropyl-2-yl).
術語「環烷氧基」表示附接到氧原子並藉由氧原子連接的環烷基，包括例如環戊基氧基和環己基氧基。術語「環烷氧基烷基」表示烷基部分上的環烷氧基取代。「環烷氧基烷基」的實例包括環丙基氧基甲基、環戊基氧基乙基以及其他鍵合到直鏈或支鏈烷基部分上的環烷氧基基團。The term "cycloalkoxy" denotes a cycloalkyl group attached to and connected through an oxygen atom, including for example cyclopentyloxy and cyclohexyloxy. The term "cycloalkoxyalkyl" denotes cycloalkoxy substitution on an alkyl moiety. Examples of "cycloalkoxyalkyl" include cyclopropyloxymethyl, cyclopentyloxyethyl and other cycloalkoxy groups bonded to linear or branched alkyl moieties.
術語「環烷基胺基烷基」表示烷基基團上的環烷基胺基取代。「環烷基胺基烷基」的實例包括環丙基胺基甲基、環戊基胺基乙基以及其他鍵合到直鏈或支鏈烷基基團上的環烷基胺基部分。The term "cycloalkylaminoalkyl" denotes cycloalkylamino substitution on an alkyl group. Examples of "cycloalkylaminoalkyl" include cyclopropylaminomethyl, cyclopentylaminoethyl, and other cycloalkylamino moieties bonded to linear or branched alkyl groups.
「三烷基矽基」包括附接到矽原子並藉由矽原子連接的3個支鏈和/或直鏈烷基，諸如三甲基矽基、三乙基矽基和三級丁基二甲基矽基。"Trialkylsilyl" includes 3 branched and/or linear alkyl groups attached to and connected through a silicon atom, such as trimethylsilyl, triethylsilyl and tertiary butyldi Methylsilyl.
術語「鹵素」，單獨地或在複合詞諸如「鹵代烷基」中，或者當在描述諸如「被鹵素取代的烷基」中使用時，包括氟、氯、溴或碘。此外，當在複合詞諸如「鹵代烷基」中使用時，或者當在描述諸如「被鹵素取代的烷基」中使用時，所述烷基可以是被鹵素原子（其可以是相同的或不同的）部分地或完全地取代的。「鹵代烷基」或「被鹵素取代的烷基」的實例包括F 3C、ClCH 2、CF 3CH 2和CF 3CCl 2。術語「鹵代環烷基」、「鹵代烷氧基」、「鹵代烷硫基」、「鹵代烷基亞磺醯基」、「鹵代烷基磺醯基」、「鹵代烯基」、「鹵代炔基」、「鹵代烷氧基烷氧基」等類似於術語「鹵代烷基」定義。「鹵代環烷基」的實例包括2-氯環丙基、2-氟環丁基、3-溴環戊基和4-氯環己基。「鹵代烷氧基」的實例包括CF 3O、CCl 3CH 2O、HCF 2CH 2CH 2O和CF 3CH 2O。「鹵代烷硫基」的實例包括CCl 3S、CF 3S、CCl 3CH 2S和ClCH 2CH 2CH 2S。「鹵代烷基亞磺醯基」的實例包括CF 3S(=O)、CCl 3S(=O)、CF 3CH 2S(=O)和CF 3CF 2S(=O)。「鹵代烷基磺醯基」的實例包括CF 3S(=O) 2、CCl 3S(=O) 2、CF 3CH 2S(=O) 2和CF 3CF 2S(=O) 2。「鹵代烯基」的實例包括Cl 2C=CHCH 2和CF 3CH 2CH=CHCH 2。「鹵代炔基」的實例包括HC≡CCHCl、CF 3C≡C、CCl 3C≡C和FCH 2C≡CCH 2。「鹵代烷氧基烷氧基」的實例包括CF 3OCH 2O、ClCH 2CH 2OCH 2CH 2O、Cl 3CCH 2OCH 2O以及支鏈烷基衍生物。 The term "halogen", alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted by halogen", includes fluorine, chlorine, bromine or iodine. Also, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted by halogen", the alkyl group may be represented by a halogen atom (which may be the same or different) Partially or completely replaced. Examples of "haloalkyl" or "alkyl substituted by halogen" include F 3 C, ClCH 2 , CF 3 CH 2 and CF 3 CCl 2 . The terms "halocycloalkyl", "haloalkoxy", "haloalkylthio", "haloalkylsulfinyl", "haloalkylsulfonyl", "haloalkenyl", "haloalkynyl ”, “haloalkoxyalkoxy”, etc. are defined similarly to the term “haloalkyl”. Examples of "halocycloalkyl" include 2-chlorocyclopropyl, 2-fluorocyclobutyl, 3-bromocyclopentyl and 4-chlorocyclohexyl. Examples of "haloalkoxy" include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O. Examples of "haloalkylthio" include CCl 3 S, CF 3 S, CCl 3 CH 2 S and ClCH 2 CH 2 CH 2 S. Examples of "haloalkylsulfinyl" include CF 3 S(=O), CCl 3 S(=O), CF 3 CH 2 S(=O) and CF 3 CF 2 S(=O). Examples of "haloalkylsulfonyl" include CF 3 S(=O) 2 , CCl 3 S(=O) 2 , CF 3 CH 2 S(=O) 2 and CF 3 CF 2 S(=O) 2 . Examples of "haloalkenyl" include Cl 2 C=CHCH 2 and CF 3 CH 2 CH=CHCH 2 . Examples of "haloalkynyl" include HC≡CCHCl, CF3C≡C , CCl3C≡C and FCH2C≡CCH2 . Examples of "haloalkoxyalkoxy" include CF 3 OCH 2 O, ClCH 2 CH 2 OCH 2 CH 2 O, Cl 3 CCH 2 OCH 2 O, and branched alkyl derivatives.
如本文所用的化學縮寫S(O)和S(=O)表示亞磺醯基部分。如本文所用的化學縮寫SO 2、S(O) 2和S(=O) 2表示磺醯基部分。如本文所用的化學縮寫C(O)和C(=O)表示羰基部分。如本文所用的化學縮寫CO 2、C(O)O和C(=O)O表示氧基羰基部分。「CHO」意指甲醯基。 The chemical abbreviations S(O) and S(=O) as used herein represent sulfinyl moieties. The chemical abbreviations SO 2 , S(0) 2 and S(=0) 2 as used herein represent sulfonyl moieties. The chemical abbreviations C(O) and C(=O) as used herein represent a carbonyl moiety. The chemical abbreviations CO2 , C(O)O and C(=O)O as used herein represent an oxycarbonyl moiety. "CHO" means methacyl.
在取代基中的碳原子的總數用「C i-C j」前綴表示，其中i和j係從1至15的數。例如，C 1-C 4烷基磺醯基表示甲基磺醯基至丁基磺醯基；C 2烷氧基烷基表示CH 3OCH 2-；C 3烷氧基烷基表示例如CH 3CH(OCH 3)-、CH 3OCH 2CH 2-或CH 3CH 2OCH 2-；並且C 4烷氧基烷基表示被包含總共四個碳原子的烷氧基基團取代的烷基基團的各種異構物，實例包括CH 3CH 2CH 2OCH 2-和CH 3CH 2OCH 2CH 2-。 The total number of carbon atoms in a substituent is indicated by the "C i -C j " prefix, where i and j are numbers from 1 to 15. For example, C 1 -C 4 alkylsulfonyl represents methylsulfonyl to butylsulfonyl; C 2 alkoxyalkyl represents CH 3 OCH 2 —; C 3 alkoxyalkyl represents such as CH 3 CH(OCH 3 )-, CH 3 OCH 2 CH 2 - or CH 3 CH 2 OCH 2 -; and C 4 alkoxyalkyl denotes an alkyl group substituted by an alkoxy group comprising a total of four carbon atoms Various isomers of the group, examples include CH 3 CH 2 CH 2 OCH 2 - and CH 3 CH 2 OCH 2 CH 2 -.
除非另外指明，否則當化合物被帶有下標的取代基取代時，該下標表示所述取代基的數目可以變化（例如，在示例1中的(R v) r，其中r係1、2、3或4），則所述取代基獨立地選自所定義的取代基的組。此外，當下標表示範圍例如(R) i-j時，則取代基的數目可以選自包括端值在內的i與j之間的整數。當基團含有可以是氫的取代基，例如R 1時，則當將該取代基視為氫時，認為這等同於所述基團係未取代的。當變數基團顯示為視需要附接到某位置時，例如示例1中的(R v) r，其中r可以是0，則氫可以在該位置，即使在變數基團的定義中沒有敘述。當基團上的一個或多個位置被稱為係「沒有被取代的」或「未取代的」時，則附接氫原子以佔據任何自由價。 Unless otherwise indicated, when a compound is substituted with a substituent, the subscript indicates that the number of said substituents may vary (e.g., (R v ) r in Example 1, where r is 1, 2, 3 or 4), then the substituents are independently selected from the defined group of substituents. In addition, when the subscript indicates a range such as (R) ij , the number of substituents can be selected from integers between i and j inclusive. When a group contains a substituent which may be hydrogen, for example R1 , then when the substituent is considered hydrogen, this is considered equivalent to that the group is unsubstituted. When a variable group is shown as being optionally attached to a position, such as (R v ) r in Example 1, where r can be 0, a hydrogen can be at that position, even if not recited in the definition of the variable group. When one or more positions on a group are said to be "unsubstituted" or "unsubstituted," then a hydrogen atom is attached to occupy any free valence.
視需要的取代基的數目可以藉由所表述的限制來限制。例如，短語「視需要被最多5個獨立地選自R JC的取代基取代」係指可以存在0、1、2、3、4或5個取代基（如果可能的連接點的數目允許的話）。當為取代基數目指定的範圍（例如，在示例1中，r為0至4的整數）超過環上可用於取代基的位置的數目（例如，在示例1中，U-9上僅有2個位置可用於(R v) r）時，該範圍的實際的較高端值被認為係可用位置的數目。 The number of optional substituents can be limited by the stated limitations. For example, the phrase "optionally substituted with up to 5 substituents independently selected from R JC " means that 0, 1, 2, 3, 4 or 5 substituents may be present (if the number of possible attachment points allows ). When the range specified for the number of substituents (e.g., in Example 1, r is an integer from 0 to 4) exceeds the number of positions available for substituents on the ring (e.g., in Example 1, only 2 on U-9 When (R v ) r ) positions are available, the actual upper end of the range is taken to be the number of available positions.
本揭露中對取代基的命名使用公認的術語，在向熟悉該項技術者準確傳達化學結構方面提供了簡潔性。為了簡潔起見，可能省略位置描述符。The use of accepted nomenclature for substituent nomenclature in this disclosure provides simplicity in accurately conveying chemical structure to those skilled in the art. Location descriptors may be omitted for brevity.
除非另外指明，否則作為式 1的組分的「環」或「環系統」係碳環或雜環。術語「環系統」表示兩個或更多個連接的環。術語「二環系統」表示由共用一個或多個共同原子的兩個環組成的環系統。「二環系統」可以是「鄰位稠合的」、「橋連二環的」或「螺二環的」。在「鄰位稠合的二環系統」中，共同的原子係相鄰的，因此環共用兩個相鄰的原子和連接它們的鍵。「橋連二環系統」藉由將一個或多個原子的鏈段鍵合至環的非相鄰環成員而形成。「螺二環系統」藉由將兩個或更多個原子的鏈段鍵合至環的相同環成員而形成。術語「稠合雜二環系統」表示其中至少一個環原子不是碳的稠合二環系統。術語「環成員」係指形成環或環系統的骨架的原子（例如，C、O、N、B或S）或其他部分（例如，C(=O)、C(=S)、S(=O)或S(=O) 2）。 Unless otherwise indicated, a "ring" or "ring system" that is a component of Formula 1 is a carbocyclic or heterocyclic ring. The term "ring system" means two or more connected rings. The term "bicyclic ring system" means a ring system consisting of two rings sharing one or more common atoms. A "bicyclic ring system" may be "ortho-fused", "bridged bicyclic" or "spirobicyclic". In an "ortho-fused bicyclic ring system", the atoms in common are adjacent so that the rings share two adjacent atoms and the bond connecting them. A "bridged bicyclic ring system" is formed by bonding a segment of one or more atoms to non-adjacent ring members of a ring. A "spirobicyclic ring system" is formed by bonding a segment of two or more atoms to the same ring member of a ring. The term "fused heterobicyclic ring system" means a fused bicyclic ring system in which at least one ring atom is not carbon. The term "ring member" refers to an atom (e.g., C, O, N, B, or S) or other moiety (e.g., C(=O), C(=S), S(= O) or S(=O) 2 ).
術語「碳環（carbocyclic ring）」、「碳環（carbocycle）」或「碳環系統」表示其中形成環骨架的原子僅選自碳的環或環系統。術語「雜環（heterocyclic ring）」、「雜環（heterocycle）」或「雜環系統」表示其中形成環骨架的至少一個原子不是碳，例如是氮、氧、硫或硼的環或環系統。典型地，雜環含有不超過4個氮、不超過2個氧、不超過2個硫和不超過1個硼。除非另外指明，否則碳環或雜環可以是飽和或不飽和的環。「飽和的」係指具有由藉由單鍵彼此連接的原子組成的骨架的環；除非另外指明，否則其餘的原子價被氫原子佔據。除非另外說明，否則「不飽和環」可以是部分不飽和的或完全不飽和的。表述「完全不飽和的環」係指原子的環，其中在該環中的原子之間的鍵根據價鍵理論係單鍵或雙鍵，並且此外該環中的原子之間的鍵包括盡可能多的雙鍵，但沒有累積雙鍵（即沒有C=C=C或C=C=N）。術語「部分不飽和的環」表示包含至少一個環成員藉由雙鍵鍵合到鄰近環成員的環，並且在概念上可能在相鄰環成員之間容納大於存在的雙鍵（即呈其部分不飽和形式）數量的多個非累積雙鍵（即，呈其完全不飽和的對應形式）。The term "carbocyclic ring", "carbocycle" or "carbocyclic ring system" means a ring or ring system in which the atoms forming the ring backbone are selected from carbons only. The term "heterocyclic ring", "heterocycle" or "heterocyclic ring system" denotes a ring or ring system in which at least one atom forming the ring backbone is other than carbon, eg nitrogen, oxygen, sulfur or boron. Typically, the heterocycle contains no more than 4 nitrogens, no more than 2 oxygens, no more than 2 sulfurs and no more than 1 boron. Unless otherwise specified, a carbocyclic or heterocyclic ring may be a saturated or unsaturated ring. "Saturated" refers to a ring having a backbone consisting of atoms joined to each other by single bonds; unless otherwise indicated, the remaining valences are occupied by hydrogen atoms. Unless otherwise stated, an "unsaturated ring" may be partially unsaturated or fully unsaturated. The expression "fully unsaturated ring" means a ring of atoms in which the bonds between the atoms in the ring are single or double bonds according to the valence bond theory, and in addition the bonds between the atoms in the ring include as far as possible Many double bonds, but no cumulative double bonds (i.e. no C=C=C or C=C=N). The term "partially unsaturated ring" means a ring comprising at least one ring member bonded by a double bond to an adjacent ring member, and it is conceptually possible to accommodate more double bonds than exist between adjacent ring members (i.e. as part of their unsaturated form) number of non-cumulative double bonds (i.e., in its fully unsaturated counterpart).
除非另外指明，否則雜環和環系統可以藉由任何可用的碳或氮藉由替換在所述碳或氮上的氫來附接。Unless otherwise indicated, heterocycles and ring systems may be attached via any available carbon or nitrogen by replacing a hydrogen on said carbon or nitrogen.
術語「芳族」表示完全不飽和的環的每個環原子基本上在同一平面中並且具有垂直於環平面的 p-軌道，並且表示(4n + 2) π個π電子（其中n係正整數）與環相關聯以符合休克爾規則（Hückel’s rule）。 The term "aromatic" means that each ring atom of a fully unsaturated ring is substantially in the same plane and has a p -orbital perpendicular to the plane of the ring, and means (4n + 2) π electrons (where n is a positive integer ) are associated with rings to comply with Hückel's rule.
術語「芳族環系統」表示其中環系統的至少一個環係芳族的碳環或雜環系統。當完全不飽和的碳環滿足休克爾規則時，則所述環還被稱為「芳族環」或「芳族碳環」。術語「芳族碳環系統」表示其中環系統的至少一個環係芳族的碳環系統。當完全不飽和的雜環滿足休克爾規則時，則所述環還被稱為「雜芳族環」或「芳族雜環」。術語「芳族雜環系統」表示其中環系統的至少一個環係芳族的雜環系統。The term "aromatic ring system" means a carbocyclic or heterocyclic ring system in which at least one ring system of the ring system is aromatic. When a fully unsaturated carbocycle satisfies Huckel's rule, then the ring is also referred to as an "aromatic ring" or "aromatic carbocycle". The term "aromatic carbocyclic ring system" means a carbocyclic ring system in which at least one ring system of the ring system is aromatic. When a fully unsaturated heterocycle satisfies Huckel's rule, then the ring is also referred to as a "heteroaromatic ring" or "aromatic heterocycle". The term "aromatic heterocyclic ring system" means a heterocyclic ring system in which at least one ring system of the ring system is aromatic.
術語「非芳族環系統」表示碳環或雜環系統，其可以是完全飽和的，以及部分或完全不飽和的，條件係環系統中沒有環係芳族的。術語「非芳族碳環系統」表示其中環系統中沒有環係芳族的碳環。術語「非芳族雜環系統」表示其中環系統中沒有環係芳族的雜環系統。The term "non-aromatic ring system" means a carbocyclic or heterocyclic ring system, which may be fully saturated, and partially or fully unsaturated, provided that none of the ring systems are aromatic. The term "non-aromatic carbocyclic ring system" means a carbocyclic ring in which none of the ring systems are aromatic. The term "non-aromatic heterocyclic ring system" means a heterocyclic ring system in which none of the ring systems are aromatic.
與雜環有關的術語「視需要取代的」係指這樣的基團，其為未取代的或具有至少一個不消除由未被取代的類似物所擁有的生物活性的非氫取代基。如本文所用，除非另外指明，否則將應用下列定義。術語「視需要取代的」與短語「被取代或未被取代的」或與術語「（未）取代的」可互換使用。除非另外指明，否則視需要取代的基團可在基團的每個可取代的位置處具有取代基，並且每個取代彼此獨立。The term "optionally substituted" in relation to heterocycles refers to groups that are unsubstituted or have at least one non-hydrogen substituent that does not abrogate the biological activity possessed by the unsubstituted analog. As used herein, the following definitions apply unless otherwise indicated. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un)substituted". Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.
當J為5員或6員含氮雜芳族環時，除非另外描述，否則其可藉由任何可用的碳或氮環原子附接到式 1的其餘部分。如上所述，J可以是（尤其）視需要被一個或多個選自如發明內容中所定義的取代基的組中的取代基取代的苯基。視需要被一至五個取代基取代的苯基的實例係如示例1中U-1所示的環，其中R v係如發明內容中對J所定義的R JC，並且r係從0至5的整數。 When J is a 5- or 6-membered nitrogen-containing heteroaromatic ring, it can be attached to the remainder of Formula 1 by any available carbon or nitrogen ring atom unless otherwise stated. As mentioned above, J may be, inter alia, phenyl optionally substituted by one or more substituents selected from the group of substituents as defined in the Summary of the Invention. An example of phenyl optionally substituted with one to five substituents is a ring as shown in U-1 in Example 1, wherein R v is R JC as defined for J in the Summary of the Invention, and r is from 0 to 5 an integer of .
如上所述，J可以是（尤其）5員或6員雜芳族環，其可以是飽和的或不飽和的，視需要被一個或多個選自如發明內容中定義的取代基的組中的取代基取代。視需要被一個或多個取代基取代的5員或6員不飽和芳族雜環的實例包括示例1中示出的環U-2至U-61，其中R v係如發明內容中針對J所定義的任何取代基（即，R JC或R JN），並且r為從0至4的整數，受限於每個U基團上可用位置的數目。由於U-29、U-30、U-36、U-37、U-38、U-39、U-40、U-41、U-42和U-43僅具有一個可用位置，所以對於該等U基團，r僅限於整數0或1，並且r為0意指U基團係未取代的，並且氫存在於由(R v) r所指示的位置處。 As mentioned above, J may be (in particular) a 5- or 6-membered heteroaromatic ring, which may be saturated or unsaturated, optionally replaced by one or more selected from the group of substituents as defined in the Summary of the Invention Substituents replace. Examples of the 5-membered or 6-membered unsaturated aromatic heterocyclic ring optionally substituted by one or more substituents include rings U-2 to U-61 shown in Example 1, wherein R v is as for J in the Summary of the Invention Any substituent as defined (ie, R JC or R JN ), and r is an integer from 0 to 4, limited by the number of available positions on each U group. Since U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42 and U-43 have only one available position, for these For a U group, r is limited to the integer 0 or 1, and r being 0 means that the U group is unsubstituted and hydrogen is present at the position indicated by (R v ) r .
示例1
注意，當J係視需要被一個或多個選自如在發明內容中對R JC所定義的取代基的組中的取代基取代的5員或6員飽和或不飽和非芳族雜環時，雜環的一個或兩個碳環成員可以視需要係羰基部分的氧化形式。 Note that when J is a 5-membered or 6-membered saturated or unsaturated non-aromatic heterocyclic ring optionally substituted by one or more substituents selected from the group of substituents as defined for R JC in the Summary of the Invention, One or both carbocyclic members of the heterocycle may optionally be an oxidized form of the carbonyl moiety.
5員或6員飽和或非芳族不飽和雜環的實例包括如示例2中所示的環G-1至G-35。應注意到，當G基團上的附接點示出為浮動時，G基團可以藉由G基團的任何可用的碳或氮藉由替換氫原子而附接到式 1的其餘部分。對應於R v的視需要的取代基可藉由替換氫原子而附接到任何可用的碳或氮上。對於該等G環，r典型地為從0至4的整數，受限於每個G基團上可用位置的數目。 Examples of the 5-membered or 6-membered saturated or nonaromatic unsaturated heterocyclic ring include rings G-1 to G-35 as shown in Example 2. It should be noted that while the point of attachment on the G group is shown as floating, the G group can be attached to the remainder of Formula 1 by replacing a hydrogen atom with any available carbon or nitrogen of the G group. Optional substituents corresponding to Rv can be attached to any available carbon or nitrogen by replacing a hydrogen atom. For such G rings, r is typically an integer from 0 to 4, limited by the number of positions available on each G group.
注意，當J包含選自G-28至G-35的環時，G 2選自O、S或N。注意，當G 2為N時，氮原子可藉由用H或對應於如發明內容中對J所定義的R v的取代基（即R JC或R JN）取代來完成其化合價。 Note that G is selected from O, S or N when J comprises a ring selected from G-28 to G-35. Note that when G2 is N, the nitrogen atom can complete its valence by substitution with H or a substituent corresponding to Rv as defined for J in the Summary of the Invention (ie R JC or R JN ).
示例2
如上所述，J可以是（尤其）視需要被一個或多個選自如發明內容中定義的取代基的組中的取代基（即R JC或R JN）取代的8員、9員或10員二環系統。視需要被一個或多個取代基取代的8、9或10員鄰位稠合的二環系統的實例包括示例3中示出的環U-81至U-124，其中R v係如發明內容中針對J所定義的任何取代基（即R JC或R JN），並且r典型地為從0至4的整數。 As stated above, J may be, inter alia, 8-, 9- or 10-membered optionally substituted with one or more substituents selected from the group of substituents as defined in the Summary of the Invention (ie R JC or R JN ) Two ring system. Examples of 8-, 9-, or 10-membered ortho-fused bicyclic ring systems optionally substituted with one or more substituents include rings U-81 to U-124 shown in Example 3, wherein Rv is as in the Summary of the Invention Any of the substituents defined for J in (ie R JC or R JN ), and r is typically an integer from 0 to 4.
示例3
雖然在結構U-1至U-124中示出R v基團，但是應注意到，因為它們係視需要的取代基，所以它們不必須存在。應注意到，當R v為H時，當附接到原子時，這如同所述原子一樣係未取代的。需要取代以填充其化合價的氮原子被H或R v取代。應注意到，當(R v) r與U基團之間的附接點示出為浮動時，(R v) r可以附接到U基團的任何可用的碳原子或氮原子。應注意到，當U基團上的附接點示出為浮動時，U基團可以藉由U基團的任何可用的碳或氮藉由替換氫原子而附接到式 1的其餘部分。應注意到，一些U基團僅能被少於4個R v基團取代（例如，U-2至U-5、U-7至U-48和U-52至U-61）。 Although R v groups are shown in structures U-1 to U-124, it should be noted that they do not have to be present as they are optional substituents. It should be noted that when Rv is H, when attached to an atom, this is unsubstituted as is said atom. Nitrogen atoms requiring substitution to fill their valences are replaced with H or Rv . It should be noted that when the point of attachment between (R v ) r and the U group is shown as floating, (R v ) r may be attached to any available carbon or nitrogen atom of the U group. It should be noted that while the point of attachment on the U group is shown as floating, the U group can be attached to the remainder of Formula 1 by replacing a hydrogen atom with any available carbon or nitrogen of the U group. It should be noted that some U groups can only be substituted with fewer than 4 Rv groups (eg, U-2 to U-5, U-7 to U-48, and U-52 to U-61).
本領域中已知多種合成方法能夠製備芳族和非芳族的雜環和環系統；對於廣泛的評論，參見八卷集的 Comprehensive Heterocyclic Chemistry[綜合雜環化學], A. R. Katritzky和C.W. Rees主編, Pergamon Press, Oxford [培格曼出版社，牛津], 1984和十二卷集的 Comprehensive Heterocyclic Chemistry II[綜合雜環化學II], A. R. Katritzky, C.W. Rees和E. F. V. Scriven主編, 培格曼出版社, 牛津, 1996。 A variety of synthetic methods are known in the art capable of preparing aromatic and nonaromatic heterocycles and ring systems; for an extensive review, see the eight-volume collection Comprehensive Heterocyclic Chemistry , edited by AR Katritzky and CW Rees, eds. Pergamon Press, Oxford, 1984 and Comprehensive Heterocyclic Chemistry II in twelve volumes, edited by AR Katritzky, CW Rees and EFV Scriven, Pergamon Press, Oxford , 1996.
本揭露之化合物可作為一種或多種立體異構物存在。立體異構物為構成相同但它們的原子在空間中的排列不同的異構物，並且包括鏡像異構物、非鏡像異構物、順-反異構物（還稱為幾何異構物）和阻轉異構物。阻轉異構物起因於圍繞單鍵的旋轉受限制，其中旋轉勢壘足夠高以允許同分異構種類的分離。熟悉該項技術者將理解，一種立體異構物當相對於一種或多種其他立體異構物富集時，或當與一種或多種其他立體異構物分離時，可能更有活性和/或可能表現出有益的效果。另外，熟悉該項技術者知道如何分離、富集和/或選擇性地製備所述立體異構物。對於立體異構現象的所有方面的綜合討論，參見Ernest L. Eliel和Samuel H. Wilen, Stereochemistry of Organic Compounds[有機化合物立體化學], John Wiley & Sons [約翰威立父子出版社], 1994。 Compounds of the present disclosure may exist as one or more stereoisomers. Stereoisomers are isomers that are identical in composition but differ in the arrangement of their atoms in space, and include enantiomers, diastereoisomers, cis-trans isomers (also known as geometric isomers) and atropisomers. Atropisomers arise from restricted rotation about a single bond, where the rotation barrier is high enough to allow separation of isomeric species. Those skilled in the art will appreciate that one stereoisomer may be more active and/or may be more active when enriched relative to one or more other stereoisomers, or when isolated from one or more other stereoisomers. exhibit beneficial effects. In addition, those skilled in the art know how to separate, enrich and/or selectively prepare said stereoisomers. For a comprehensive discussion of all aspects of the phenomenon of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds , John Wiley & Sons, 1994.
本揭露之化合物可以作為立體異構物的混合物或單獨的立體異構物存在。例如，式
1的四種可能的立體異構物描述為式
1
i 、式
1
ii 、式
1
iii 和式
1
iv ，關於用星號（*）標識的三個環丙烷手性中心。類似地，在例如R
1處可能有其他手性中心。
本文繪製的分子描述依照用於描繪立體化學的標準慣例。為了指明立體組態，從繪圖平面伸出並且朝向觀看者的鍵以實心楔形表示，其中該楔形的寬端連接至從繪圖平面伸出朝向觀看者的原子上。伸向繪圖平面下方並且遠離觀察者的鍵由虛線楔形表示，其中該楔形的寬端連接到進一步遠離觀察者的原子上。Molecular descriptions drawn herein follow standard conventions for depicting stereochemistry. To indicate the three-dimensional configuration, bonds protruding from the plane of the drawing and facing the viewer are represented by solid wedges, where the wide end of the wedge is attached to an atom protruding from the plane of the drawing and facing the viewer. Bonds extending below the drawing plane and away from the viewer are represented by dashed wedges with the wide end of the wedge attached to atoms further away from the viewer.
由於式 1中可能存在手性碳原子，本揭露之化合物可以作為立體異構物存在。因此，本揭露包括式 1的化合物的單獨的立體異構物，以及式 1的化合物的立體異構物的混合物。 Due to the possible presence of chiral carbon atoms in Formula 1 , the compounds of the present disclosure may exist as stereoisomers. Accordingly, the present disclosure includes individual stereoisomers of the compound of Formula 1 , as well as mixtures of stereoisomers of the compound of Formula 1 .
本揭露包括等量的式 1 i 和 1 ii 的鏡像異構物的外消旋混合物。此外，本揭露包括與式 1 i 和 1 ii 的外消旋混合物相比富含式 1 i 鏡像異構物的混合物。本揭露還包括基本上純的式 1 i 的鏡像異構物。 The present disclosure includes racemic mixtures of equivalent amounts of enantiomers of Formulas 1 i and 1 ii . Furthermore, the present disclosure includes mixtures enriched in the enantiomer of Formula 1 i as compared to the racemic mixture of Formulas 1 i and 1 ii . The present disclosure also includes substantially pure enantiomers of Formula 1 i .
本揭露之實施方式包括式 1 i 和式 1 ii 的化合物的立體異構物的混合物，其中 1 i 與 1 ii 的比率為至少75 : 25（ 1 i 50%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula 1 i and formula 1 ii , wherein the ratio of 1 i to 1 ii is at least 75:25 (50% enantiomer excess of 1 i ).
本揭露之實施方式包括式 1 i 和式 1 ii 的化合物的立體異構物的混合物，其中 1 i 與 1 ii 的比率為至少90 : 10（ 1 i 80%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula 1 i and formula 1 ii , wherein the ratio of 1 i to 1 ii is at least 90:10 (80% enantiomer excess of 1 i ).
本揭露之實施方式包括式 1 i 和式 1 ii 的化合物的立體異構物的混合物，其中 1 i 與 1 ii 的比率為至少95 : 5（ 1 i 90%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula 1 i and formula 1 ii , wherein the ratio of 1 i to 1 ii is at least 95:5 (90% enantiomer excess of 1 i ).
本揭露之實施方式包括式 1 i 和式 1 ii 的化合物的立體異構物的混合物，其中 1 i 與 1 ii 的比率為至少98 : 2（ 1 i 96%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula 1 i and formula 1 ii , wherein the ratio of 1 i to 1 ii is at least 98:2 ( 1 i 96% enantiomer excess).
本揭露之實施方式包括式 1 i 和式 1 ii 的化合物的立體異構物的混合物，其中 1 i 與 1 ii 的比率為至少99 : 1（ 1 i 98%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula 1 i and formula 1 ii , wherein the ratio of 1 i to 1 ii is at least 99:1 ( 1 i 98% enantiomer excess).
本揭露之實施方式包括式 1 i 和式 1 ii 的化合物的立體異構物的混合物，其中 1 i 與 1 ii 的比率基本上為100 : 0。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula 1 i and formula 1 ii , wherein the ratio of 1 i to 1 ii is substantially 100:0.
本揭露之實施方式包括式 1 i 的化合物。 Embodiments of the present disclosure include compounds of formula 1i .
此外，本揭露包括與式 1 ii 和 1 i 的外消旋混合物相比富含式 1 ii 鏡像異構物的混合物。本揭露還包括基本上純的式 1 ii 的鏡像異構物。 Furthermore, the present disclosure includes mixtures enriched in the enantiomer of Formula 1 ii as compared to racemic mixtures of Formulas 1 ii and 1 i . The present disclosure also includes substantially pure enantiomers of Formula 1 ii .
本揭露之實施方式包括式 1 ii 和式 1 i 的化合物的立體異構物的混合物，其中 1 ii 與 1 i 的比率為至少75 : 25（ 1 ii 50%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula ii and formula 1i , wherein the ratio of 1ii to 1i is at least 75:25 (50% enantiomer excess of 1ii ).
本揭露之實施方式包括式 1 ii 和式 1 i 的化合物的立體異構物的混合物，其中 1 ii 與 1 i 的比率為至少90 : 10（ 1 ii 80%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula ii and 1 i , wherein the ratio of 1 ii to 1 i is at least 90:10 (80% enantiomer excess of 1 ii ).
本揭露之實施方式包括式 1 ii 和式 1 i 的化合物的立體異構物的混合物，其中 1 ii 與 1 i 的比率為至少95 : 5（ 1 ii 90%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of the compounds of formula 1ii and 1i , wherein the ratio of 1ii to 1i is at least 95:5 (90% enantiomer excess of 1ii ).
本揭露之實施方式包括式 1 ii 和式 1 i 的化合物的立體異構物的混合物，其中 1 ii 與 1 i 的比率為至少98 : 2（ 1 ii 96%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of the compounds of formula 1ii and 1i , wherein the ratio of 1ii to 1i is at least 98:2 (96% enantiomer excess of 1ii ).
本揭露之實施方式包括式 1 ii 和式 1 i 的化合物的立體異構物的混合物，其中 1 ii 與 1 i 的比率為至少99 : 1（ 1 ii 98%鏡像異構物過量）。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula ii and formula 1i , wherein the ratio of 1ii to 1i is at least 99:1 (98% enantiomer excess of 1ii ).
本揭露之實施方式包括式 1 ii 和式 1 i 的化合物的立體異構物的混合物，其中 1 ii 與 1 i 的比率基本上為100 : 0。 Embodiments of the present disclosure include mixtures of stereoisomers of compounds of formula ii and formula 1i , wherein the ratio of 1ii to 1i is substantially 100:0.
本揭露之實施方式包括式 1 ii 的化合物。 Embodiments of the present disclosure include compounds of formula ii .
式 1的化合物可包含附加的手性中心。例如，取代基和其他分子成分諸如Y本身可以含有手性中心。本揭露包括外消旋混合物以及在該等附加的手性中心處富集的和基本上純的立體組態。 Compounds of Formula 1 may contain additional chiral centers. For example, substituents and other molecular components such as Y itself may contain chiral centers. The present disclosure includes racemic mixtures as well as enriched and substantially pure stereoconfigurations at such additional chiral centers.
本揭露之化合物由於圍繞式 1中的醯胺鍵（例如，C(=O)-N）的旋轉受限，因此可以作為一種或多種構象異構物存在。本揭露包括構象異構物的混合物。此外，本揭露包括一種構象異構物相對於其他構象異構物富集的化合物。 Compounds of the present disclosure may exist as one or more conformational isomers due to restricted rotation about the amide bond in Formula 1 (eg, C(=0)-N). The present disclosure includes mixtures of conformers. Additionally, the present disclosure includes compounds that are enriched in one conformer relative to the other.
本揭露包括所有立體異構物、構象異構物及其所有比例的混合物以及同位素形式諸如氘化化合物。The disclosure includes all stereoisomers, conformers and mixtures thereof in all ratios as well as isotopic forms such as deuterated compounds.
熟悉該項技術者將理解，不是所有的含氮雜環都可以形成 N-氧化物，因為氮需要可用的孤電子對以氧化成氧化物；熟悉該項技術者將認識到可形成 N-氧化物的那些含氮雜環。熟悉該項技術者還將認識到三級胺能夠形成 N-氧化物。用於製備雜環和三級胺的 N-氧化物的合成方法係熟悉該項技術者非常熟知的，包括使用過氧酸諸如過氧乙酸和3-氯過氧苯甲酸（MCPBA）、過氧化氫、烷基氫過氧化物諸如三級丁基氫過氧化物、過硼酸鈉和二環氧乙烷諸如二甲基二環氧乙烷來氧化雜環和三級胺。用於製備 N-氧化物的該等方法已廣泛描述和綜述於文獻中，參見例如：T. L. Gilchrist, Comprehensive Organic Synthesis[綜合有機合成], 第7卷, 第748-750頁, S. V. Ley編輯, 培格曼出版社；M. Tisler和B. Stanovnik， Comprehensive Heterocyclic Chemistry[綜合雜環化學], 第3卷, 第18-20頁, A. J. Boulton和A. McKillop編輯, 培格曼出版社；M. R. Grimmett和B. R. T. Keene, Advances in Heterocyclic Chemistry[雜環化學進展], 第43卷, 第149-161頁, A. R. Katritzky編輯, Academic Press [學術出版社]；M. Tisler和B. Stanovnik, Advances in Heterocyclic Chemistry[雜環化學進展], 第9卷, 第285-291頁, A. R. Katritzky和A. J. Boulton編輯, 學術出版社；和G. W. H. Cheeseman和E. S. G. Werstiuk, Advances in Heterocyclic Chemistry[雜環化學進展], 第22卷, 第390-392頁, A. R. Katritzky和A. J. Boulton編輯, 學術出版社。 Those skilled in the art will understand that not all nitrogen-containing heterocycles can form N- oxides, since nitrogen requires an available lone electron pair to oxidize to an oxide; those skilled in the art will recognize that N- oxides can form Those nitrogen-containing heterocycles. Those skilled in the art will also recognize that tertiary amines are capable of forming N- oxides. Synthetic methods for the preparation of N -oxides of heterocycles and tertiary amines are well known to those skilled in the art and include the use of peroxyacids such as peracetic acid and 3-chloroperoxybenzoic acid (MCPBA), peroxy Hydrogen, alkyl hydroperoxides such as tertiary butyl hydroperoxide, sodium perborate, and dioxirane such as dimethyldioxirane to oxidize heterocycles and tertiary amines. Such methods for the preparation of N -oxides have been extensively described and reviewed in the literature, see for example: TL Gilchrist, Comprehensive Organic Synthesis [Comprehensive Organic Synthesis], Vol. 7, pp. 748-750, edited by SV Ley, Pei Geman Press; M. Tisler and B. Stanovnik, Comprehensive Heterocyclic Chemistry , Volume 3, pp. 18-20, edited by AJ Boulton and A. McKillop, Pegman Press; MR Grimmett and BRT Keene, Advances in Heterocyclic Chemistry , Vol. 43, pp. 149-161, edited by AR Katritzky, Academic Press; M. Tisler and B. Stanovnik, Advances in Heterocyclic Chemistry [Miscellaneous Advances in Heterocyclic Chemistry], Vol. 9, pp. 285-291, edited by AR Katritzky and AJ Boulton, Academic Press; and GWH Cheeseman and ESG Werstiuk, Advances in Heterocyclic Chemistry , Vol. 22, No. 390 -392 pages, edited by AR Katritzky and AJ Boulton, Academic Press.
熟悉該項技術者認識到，由於在環境中和在生理條件下化合物的鹽與它們相應的非鹽形式處於平衡，因此鹽共用非鹽形式的生物效用。因此，多種式 1的化合物的鹽可用於防治無脊椎害蟲。式 1的化合物的鹽包括與無機酸或有機酸形成的酸加成鹽，該等酸諸如氫溴酸、鹽酸、硝酸、磷酸、硫酸、乙酸、丁酸、富馬酸、乳酸、馬來酸、丙二酸、草酸、丙酸、水楊酸、酒石酸、4-甲苯磺酸或戊酸。當式 1的化合物包含酸性部分諸如羧酸或酚時，鹽還包括與有機鹼或無機鹼形成的那些，該等鹼諸如吡啶、三乙胺或氨、或鈉、鉀、鋰、鈣、鎂或鋇的醯胺、氫化物、氫氧化物或碳酸鹽。因此，本揭露包括選自式 1的化合物、其 N-氧化物和合適的鹽。 Those skilled in the art recognize that since salts of compounds are in equilibrium with their corresponding non-salt forms in the environment and under physiological conditions, salts share the biological utility of the non-salt forms. Thus, various salts of compounds of formula 1 are useful for controlling invertebrate pests. Salts of compounds of formula 1 include acid addition salts formed with inorganic or organic acids such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid , malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid. When the compound of formula 1 contains an acidic moiety such as carboxylic acid or phenol, salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or sodium, potassium, lithium, calcium, magnesium Or barium amides, hydrides, hydroxides or carbonates. Accordingly, the present disclosure includes compounds selected from Formula 1 , N- oxides and suitable salts thereof.
選自式 1的化合物、其立體異構物、互變異構物、 N-氧化物和鹽典型地以多於一種形式存在，並且因此式 1包括式 1所代表的化合物的所有結晶和非結晶形式。非結晶形式包括為固體的實施方式諸如蠟和樹膠，以及為液體的實施方式諸如溶液和熔融物。結晶形式包括代表基本上單晶類型的實施方式和代表多晶型物（即不同結晶類型）的混合物的實施方式。術語「多晶型物」係指可以以不同晶型結晶的化合物的具體晶型，該等晶型在晶格中具有不同的分子排列和/或構象。雖然多晶型物可具有相同的化學組成，但是它們也可以在組成上由於共結晶水或其他分子的存在或不存在而不同，該共結晶水或其他分子可弱結合或強結合在晶格內。多晶型物可以在此類化學、物理、和生物特性方面不同，諸如晶體形狀、密度、硬度、顏色、化學穩定性、熔點、吸濕性、可懸浮性、溶解速率和生體可用率。熟悉該項技術者將理解，相對於由式 1表示的相同化合物的另一種多晶型物或多晶型物的混合物，由式 1表示的化合物的多晶型物可以展現出有益效果（例如適合製備有用製劑，改善的生物性能）。由式 1表示的化合物的具體多晶型物的製備和分離可藉由熟悉該項技術者已知之方法實現，包括例如採用所選溶劑和溫度的結晶。本揭露之化合物可作為一種或多種結晶多晶型物存在。本揭露包含單獨多晶型物和多晶型物的混合物二者，包括相對於其他富集多晶型物一種多晶型物的混合物。對於多晶型現象的綜合討論，參見R. Hilfiker編輯, Polymorphism in the Pharmaceutical Industry[製藥工業的多晶型現象], Wiley-VCH, Weinheim [魏因海姆], 2006。 Compounds selected from Formula 1 , stereoisomers, tautomers, N -oxides and salts thereof typically exist in more than one form, and thus Formula 1 includes all crystalline and non-crystalline forms of the compound represented by Formula 1 form. Amorphous forms include solid embodiments such as waxes and gums, and liquid embodiments such as solutions and melts. Crystalline forms include embodiments representing substantially single crystal types and embodiments representing mixtures of polymorphs (ie, different crystal types). The term "polymorph" refers to a specific crystal form of a compound that can crystallize in different crystal forms having different molecular arrangements and/or conformations in the crystal lattice. While polymorphs can have the same chemical composition, they can also differ in composition due to the presence or absence of co-crystallized water or other molecules that can be weakly or strongly bound in the crystal lattice Inside. Polymorphs can differ in such chemical, physical, and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, dissolution rate, and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 may exhibit beneficial effects relative to another polymorph or mixture of polymorphs of the same compound represented by Formula 1 (e.g. Suitable for preparation of useful formulations, improved biological properties). The preparation and isolation of specific polymorphs of the compound represented by Formula 1 can be achieved by methods known to those skilled in the art, including, for example, crystallization using the chosen solvent and temperature. Compounds of the present disclosure may exist as one or more crystalline polymorphs. The present disclosure encompasses both individual polymorphs and mixtures of polymorphs, including mixtures of one polymorph relative to other enriched polymorphs. For a comprehensive discussion of polymorphism, see R. Hilfiker ed., Polymorphism in the Pharmaceutical Industry [Polymorphism in the Pharmaceutical Industry], Wiley-VCH, Weinheim, 2006.
本揭露之如發明內容中所描述的實施方式包括以下描述的那些。在以下實施方式中，除非在實施方式中進一步定義，否則式 1包括其立體異構物、 N-氧化物和鹽，並且對「式 1的化合物」的提及包括在發明內容中指定的取代基的定義。 Embodiments of the present disclosure, as described in the Summary of the Invention, include those described below. In the following embodiments, unless further defined in the embodiments, Formula 1 includes its stereoisomers, N -oxides and salts, and references to "compounds of Formula 1 " include the substitutions specified in the Summary of the Invention base definition.
實施方式1. 一種具有 1的化合物，其中R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 1-C 4烷硫基、C 1-C 4鹵代烷硫基、C 1-C 4烷基亞磺醯基、C 1-C 4鹵代烷基亞磺醯基、C 1-C 4烷基磺醯基或C 1-C 4鹵代烷基磺醯基。 Embodiment 1. A compound having 1 , wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 1 -C 4 alkylsulfinyl, C 1 - C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfonyl or C 1 -C 4 haloalkylsulfinyl.
實施方式1a. 如實施方式1所述之化合物，其中R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、氰基、C 1-C 3烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基、C 1-C 2烷硫基、C 1-C 2鹵代烷硫基、C 1-C 2烷基亞磺醯基、C 1-C 2鹵代烷基亞磺醯基、C 1-C 2烷基磺醯基或C 1-C 2鹵代烷基磺醯基。 Embodiment 1a. The compound of Embodiment 1, wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, cyano, C 1 -C 3 alkyl, C 1 -C 2 haloalkane C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, C 1 -C 2 alkylthio, C 1 -C 2 haloalkylthio, C 1 -C 2 alkylsulfinyl, C 1 -C 2 haloalkylsulfinyl, C 1 -C 2 alkylsulfonyl or C 1 -C 2 haloalkylsulfonyl.
實施方式1b. 如實施方式1a所述之化合物，其中R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基。 Embodiment 1b. The compound of Embodiment 1a, wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
實施方式1c. 如實施方式1b所述之化合物，其中R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、甲基、乙基、異丙基或C 1-C 2鹵代烷基。 Embodiment 1c. The compound according to embodiment 1b, wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, methyl, ethyl, isopropyl or C 1 -C 2 haloalkyl .
實施方式2. 如式 1或前述實施方式中任一項所述之化合物，其中R 1、R 2、R 3和R 4各自獨立地是氫、鹵素或甲基。 Embodiment 2. The compound of Formula 1 or any one of the preceding embodiments, wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen or methyl.
實施方式2a. 如式 1或前述實施方式中任一項所述之化合物，其中R 1、R 2、R 3和R 4各自係氫。 Embodiment 2a. The compound of Formula 1 or any one of the preceding embodiments, wherein R 1 , R 2 , R 3 and R 4 are each hydrogen.
實施方式3a. 如式 1或前述實施方式中任一項所述之化合物，其中R 5、R 6和R 7各自獨立地是氫、鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 1-C 4烷硫基、C 1-C 4鹵代烷硫基、C 1-C 4烷基亞磺醯基、C 1-C 4鹵代烷基亞磺醯基、C 1-C 4烷基磺醯基或C 1-C 4鹵代烷基磺醯基。 Embodiment 3a. The compound of formula 1 or any one of the preceding embodiments, wherein R 5 , R 6 and R 7 are each independently hydrogen, halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 1 -C 4 alkylene Sulfonyl, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfonyl or C 1 -C 4 haloalkylsulfinyl.
實施方式3a1. 如式 1或實施方式1至2a中任一項所述之化合物，其中R 5、R 6和R 7各自獨立地是氫、鹵素、氰基、C 1-C 3烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基、C 1-C 2烷硫基、C 1-C 2鹵代烷硫基、C 1-C 2烷基亞磺醯基、C 1-C 2鹵代烷基亞磺醯基、C 1-C 2烷基磺醯基、C 1-C 2鹵代烷基磺醯基或Q 1。 Embodiment 3a1. A compound according to Formula 1 or any one of Embodiments 1 to 2a, wherein R 5 , R 6 and R 7 are each independently hydrogen, halogen, cyano, C 1 -C 3 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, C 1 -C 2 alkylthio, C 1 -C 2 haloalkylthio, C 1 -C 2 alkane Sulfinyl, C 1 -C 2 haloalkylsulfinyl, C 1 -C 2 alkylsulfinyl, C 1 -C 2 haloalkylsulfinyl or Q 1 .
實施方式3b. 如實施方式3a或3a1所述之化合物，其中R 5、R 6和R 7各自獨立地是氫、鹵素、氰基、C 1-C 3烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基、C 1-C 2烷硫基、C 1-C 2鹵代烷硫基、C 1-C 2烷基亞磺醯基、C 1-C 2鹵代烷基亞磺醯基、C 1-C 2烷基磺醯基或C 1-C 2鹵代烷基磺醯基。 Embodiment 3b. The compound according to Embodiment 3a or 3a1, wherein R 5 , R 6 and R 7 are each independently hydrogen, halogen, cyano, C 1 -C 3 alkyl, C 1 -C 2 haloalkyl , C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, C 1 -C 2 alkylthio, C 1 -C 2 haloalkylthio, C 1 -C 2 alkylsulfinyl, C 1 -C 2 haloalkylsulfinyl, C 1 -C 2 alkylsulfonyl or C 1 -C 2 haloalkylsulfinyl.
實施方式3c. 如實施方式3a所述之化合物，其中R 5、R 6和R 7各自獨立地是氫、鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基。 Embodiment 3c. The compound of embodiment 3a, wherein R 5 , R 6 and R 7 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
實施方式3d. 如實施方式3c所述之化合物，其中R 5、R 6和R 7各自獨立地是氫、鹵素、甲基、乙基、異丙基或C 1-C 2鹵代烷基。 Embodiment 3d. The compound of embodiment 3c, wherein R 5 , R 6 and R 7 are each independently hydrogen, halogen, methyl, ethyl, isopropyl or C 1 -C 2 haloalkyl.
實施方式3e. 如式 1或前述實施方式中任一項所述之化合物，其中R 5、R 6和R 7各自獨立地是氫、鹵素或甲基。 Embodiment 3e. The compound of Formula 1 or any one of the preceding embodiments, wherein R 5 , R 6 and R 7 are each independently hydrogen, halogen or methyl.
實施方式3f. 如式 1或前述實施方式中任一項所述之化合物，其中R 5、R 6和R 7各自係氫。 Embodiment 3f. The compound of Formula 1 or any one of the preceding embodiments, wherein each of R5 , R6 and R7 is hydrogen.
實施方式4a. 如式 1或前述實施方式中任一項所述之化合物，其中Q 1係6員至10員碳環或環系統，每個環或環系統視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 1-C 4烷硫基、C 1-C 4鹵代烷硫基、C 1-C 4烷基亞磺醯基、C 1-C 4鹵代烷基亞磺醯基、C 1-C 4烷基磺醯基和C 1-C 4鹵代烷基磺醯基。 Embodiment 4a. The compound as described in formula 1 or any one of the preceding embodiments, wherein Q 1 is a 6-membered to 10-membered carbocyclic ring or ring system, each ring or ring system is optionally represented by one or more independently Substituents selected from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 Alkylthio, C 1 -C 4 Haloalkylthio, C 1 -C 4 Alkylsulfinyl, C 1 -C 4 Haloalkylsulfinyl, C 1 -C 4 Alkylsulfinyl and C 1 -C 4 haloalkylsulfonyl.
實施方式4b. 如實施方式4a所述之化合物，其中Q 1係6員至8員芳族碳環，每個環視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 1-C 4烷硫基、C 1-C 4鹵代烷硫基、C 1-C 4烷基亞磺醯基、C 1-C 4鹵代烷基亞磺醯基、C 1-C 4烷基磺醯基和C 1-C 4鹵代烷基磺醯基。 Embodiment 4b. The compound as described in Embodiment 4a, wherein Q 1 is a 6-membered to 8-membered aromatic carbocyclic ring, and each ring is optionally substituted by one or more substituents independently selected from the following: halogen, Cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 Haloalkylthio, C 1 -C 4 Alkylsulfinyl, C 1 -C 4 Haloalkylsulfinyl, C 1 -C 4 Alkylsulfonyl and C 1 -C 4 Haloalkylsulfinyl .
實施方式4c. 如式 1或實施方式1至3f中任一項所述之化合物，其中Q 1係6員至14員碳環或環系統，每個環或環系統視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C 1-C 4烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基。 Embodiment 4c. A compound as described in any one of Formula 1 or Embodiments 1 to 3f, wherein Q is a 6- to 14-membered carbon ring or ring system, each ring or ring system being optionally replaced by one or more Substituents independently selected from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy .
實施方式4d. 如實施方式4c所述之化合物，其中Q 1係6員至10員碳環或環系統，每個環或環系統視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C 1-C 4烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基。 Embodiment 4d. The compound as described in embodiment 4c, wherein Q 1 is a 6-membered to 10-membered carbocyclic ring or ring system, each ring or ring system is optionally substituted by one or more independently selected from the following Base substitution: halogen, cyano, C 1 -C 4 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy.
實施方式4e. 如實施方式4d所述之化合物，其中Q 1係6員至8員芳族碳環，每個環視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C 1-C 4烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基。 Embodiment 4e. The compound as described in Embodiment 4d, wherein Q 1 is a 6-membered to 8-membered aromatic carbocyclic ring, and each ring is optionally substituted by one or more substituents independently selected from the following: halogen, Cyano, C 1 -C 4 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy.
實施方式5a. 如式 1或實施方式1至4e中任一項所述之化合物，其中W係O。 Embodiment 5a. The compound of Formula 1 or any one of Embodiments 1 to 4e, wherein W is O.
實施方式5b. 如式 1或實施方式1至4e中任一項所述之化合物，其中W係S。 Embodiment 5b. The compound of Formula 1 or any one of Embodiments 1 to 4e, wherein W is S.
實施方式6a. 如式 1或前述實施方式中任一項所述之化合物，其中Y係氫、C(=O)R 8、S(=O) nR 9、CO 2R 10、C(=O)NR 11R 12、S(=O) nNR 11R 12、NR 11R 12、C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基、C 1-C 6鹵代烷基、C 2-C 6鹵代烯基、C 2-C 6鹵代炔基、C 3-C 8環烷基、C 3-C 8鹵代環烷基、C 3-C 8環烯基、C 3-C 8鹵代環烯基、C 4-C 10烷基環烷基、C 4-C 10環烷基烷基、C 4-C 10鹵代環烷基烷基、C 6-C 14環烷基環烷基、C 5-C 10烷基環烷基烷基、C 2-C 8烷氧基烷基、C 2-C 8鹵代烷氧基烷基、C 4-C 10環烷氧基烷基、C 3-C 8烷氧基烷氧基烷基、C 2-C 6烷硫基烷基、C 2-C 6烷基亞磺醯基烷基、C 2-C 6烷基磺醯基烷基、C 2-C 6烷基胺基烷基、C 2-C 6鹵代烷基胺基烷基、C 3-C 8二烷基胺基烷基、C 4-C 10環烷基胺基烷基或C 3-C 5烷氧基羰基烷基。 Embodiment 6a. The compound according to formula 1 or any one of the preceding embodiments, wherein Y is hydrogen, C(=O)R 8 , S(=O) n R 9 , CO 2 R 10 , C(= O)NR 11 R 12 , S(=O) n NR 11 R 12 , NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 - C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C 3 -C 8 Cycloalkenyl, C 3 -C 8 halocycloalkenyl, C 4 -C 10 alkylcycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 10 halocycloalkylalkyl, C 6 -C 14 cycloalkylcycloalkyl, C 5 -C 10 alkylcycloalkylalkyl, C 2 -C 8 alkoxyalkyl, C 2 -C 8 haloalkoxyalkyl, C 4 - C 10 cycloalkoxyalkyl, C 3 -C 8 alkoxyalkoxyalkyl, C 2 -C 6 alkylthioalkyl, C 2 -C 6 alkylsulfinylalkyl, C 2 -C 6 alkylsulfonylalkyl, C 2 -C 6 alkylaminoalkyl, C 2 -C 6 haloalkylaminoalkyl, C 3 -C 8 dialkylaminoalkyl, C 4 -C 10 cycloalkylaminoalkyl or C 3 -C 5 alkoxycarbonylalkyl.
實施方式6b. 如式 1或實施方式1至5b中任一項所述之化合物，其中Y係氫、C(=O)R 8、S(=O) nR 9、CO 2R 10、C(=O)NR 11R 12、S(=O) nNR 11R 12或NR 11R 12；或視需要在環成員上被R 13取代的苄基；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基、C 1-C 6鹵代烷基、C 2-C 6鹵代烯基、C 2-C 6鹵代炔基、C 3-C 8環烷基、C 2-C 8烷氧基烷基、C 2-C 8鹵代烷氧基烷基、C 2-C 6烷硫基烷基、C 2-C 6烷基亞磺醯基烷基、C 2-C 6烷基磺醯基烷基、C 2-C 6烷基胺基烷基、C 2-C 6鹵代烷基胺基烷基、C 3-C 8二烷基胺基烷基、C 4-C 10環烷基胺基烷基或C 3-C 5烷氧基羰基烷基，各自視需要被最多1個選自以下各項的取代基取代：氰基、羥基、硝基、C 2-C 4烷基羰基、C 2-C 4烷氧基羰基。 Embodiment 6b. The compound according to any one of Formula 1 or Embodiments 1 to 5b, wherein Y is hydrogen, C(=O)R 8 , S(=O) n R 9 , CO 2 R 10 , C (=O)NR 11 R 12 , S(=O) n NR 11 R 12 or NR 11 R 12 ; or benzyl optionally substituted by R 13 on a ring member; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 8 cycloalkane C 2 -C 8 alkoxyalkyl, C 2 -C 8 haloalkoxyalkyl, C 2 -C 6 alkylthioalkyl, C 2 -C 6 alkylsulfinylalkyl, C 2 -C 6 alkylsulfonylalkyl, C 2 -C 6 alkylaminoalkyl, C 2 -C 6 haloalkylaminoalkyl, C 3 -C 8 dialkylaminoalkyl, C 4 -C 10 cycloalkylaminoalkyl or C 3 -C 5 alkoxycarbonylalkyl, each optionally substituted by up to 1 substituent selected from the group consisting of cyano, hydroxy, nitro, C 2 -C 4 alkylcarbonyl, C 2 -C 4 alkoxycarbonyl.
實施方式6c. 如實施方式6a或6b所述之化合物，其中Y係氫、C(=O)R 8、S(=O) nR 9、CO 2R 10、C(=O)NR 11R 12、S(=O) nNR 11R 12、NR 11R 12、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 3-C 6環烷基、C 2-C 4烷氧基烷基、C 2-C 4鹵代烷氧基烷基、C 2-C 4烷硫基烷基、C 2-C 4烷基亞磺醯基烷基、C 2-C 4烷基磺醯基烷基、C 2-C 4烷基胺基烷基、C 2-C 4鹵代烷基胺基烷基、C 3-C 5二烷基胺基烷基、C 4-C 7環烷基胺基烷基或C 3-C 5烷氧基羰基烷基。 Embodiment 6c. The compound as described in Embodiment 6a or 6b, wherein Y is hydrogen, C(=O)R 8 , S(=O) n R 9 , CO 2 R 10 , C(=O)NR 11 R 12. S(=O) n NR 11 R 12 , NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkoxyalkyl, C 2 -C 4 haloalkoxyalkyl , C 2 -C 4 alkylthioalkyl, C 2 -C 4 alkylsulfinylalkyl, C 2 -C 4 alkylsulfonylalkyl, C 2 -C 4 alkylaminoalkyl , C 2 -C 4 haloalkylaminoalkyl, C 3 -C 5 dialkylaminoalkyl, C 4 -C 7 cycloalkylaminoalkyl or C 3 -C 5 alkoxycarbonylalkyl .
實施方式6d. 如實施方式6c所述之化合物，其中Y係氫、C(=O)R 8、S(=O) nR 9、CO 2R 10、C(=O)NR 11R 12、S(=O) nNR 11R 12、NR 11R 12或C 1-C 6烷基。 Embodiment 6d. The compound as described in Embodiment 6c, wherein Y is hydrogen, C(=O)R 8 , S(=O) n R 9 , CO 2 R 10 , C(=O)NR 11 R 12 , S(=O) n NR 11 R 12 , NR 11 R 12 or C 1 -C 6 alkyl.
實施方式6e. 如實施方式6c所述之化合物，其中Y係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 3-C 6環烷基。 Embodiment 6e. The compound as described in Embodiment 6c, wherein Y is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 cycloalkyl.
實施方式6f. 如式 1或前述實施方式中任一項所述之化合物，其中Y係氫或C 1-C 6烷基。 Embodiment 6f. The compound of Formula 1 or any one of the preceding embodiments, wherein Y is hydrogen or C 1 -C 6 alkyl.
實施方式6g. 如實施方式6f所述之化合物，其中Y係氫或C 1-C 4烷基。 Embodiment 6g. The compound of embodiment 6f, wherein Y is hydrogen or C 1 -C 4 alkyl.
實施方式6h. 如實施方式6g所述之化合物，其中Y係氫、甲基、乙基或異丙基。Embodiment 6h. The compound according to Embodiment 6g, wherein Y is hydrogen, methyl, ethyl or isopropyl.
實施方式6i. 如實施方式6h所述之化合物，其中Y係氫或甲基。Embodiment 6i. The compound of embodiment 6h, wherein Y is hydrogen or methyl.
實施方式6j. 如實施方式6i所述之化合物，其中Y係氫。Embodiment 6j. The compound of embodiment 6i, wherein Y is hydrogen.
實施方式7a. 如式 1或前述實施方式中任一項所述之化合物，其中R 8、R 9和R 10各自獨立地是C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 2-C 6鹵代烯基、C 2-C 6鹵代炔基、C 2-C 7烷氧基烷基或C 4-C 7環烷基烷基；或視需要被R 13取代的苯基。 Embodiment 7a. The compound of formula 1 or any one of the preceding embodiments, wherein R 8 , R 9 and R 10 are each independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 2 -C 7 alkane oxyalkyl or C 4 -C 7 cycloalkylalkyl; or phenyl optionally substituted by R 13 .
實施方式7b. 如實施方式7a所述之化合物，其中R 8、R 9和R 10各自獨立地是C 1-C 3烷基、C 2-C 3烯基、C 2-C 3炔基、C 3-C 6環烷基或C 1-C 3鹵代烷基。 Embodiment 7b. The compound according to Embodiment 7a, wherein R 8 , R 9 and R 10 are each independently C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C 3 -C 6 cycloalkyl or C 1 -C 3 haloalkyl.
實施方式7c. 如實施方式7b所述之化合物，其中R 8、R 9和R 10各自獨立地是C 1-C 3烷基或C 1-C 2鹵代烷基。 Embodiment 7c. The compound of embodiment 7b, wherein R 8 , R 9 and R 10 are each independently C 1 -C 3 alkyl or C 1 -C 2 haloalkyl.
實施方式8a. 如式 1或前述實施方式中任一項所述之化合物，其中R 11係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 2-C 7烷氧基烷基、C 4-C 7環烷基烷基、C 2-C 4烷硫基烷基、C 1-C 4烷基磺醯基、C 1-C 4鹵代烷基磺醯基、C 2-C 4烷基亞磺醯基烷基、C 2-C 4烷基磺醯基烷基、C 2-C 4烷基羰基、C 2-C 4鹵代烷基羰基、C 2-C 5烷氧基羰基、C 3-C 5烷氧基羰基烷基、C 2-C 5烷基胺基羰基、C 3-C 5二烷基胺基羰基、C 3-C 7烷基胺基羰基烷基或C 4-C 7二烷基胺基羰基烷基；或視需要被R 13取代的苯基；或視需要在環成員上被R 13取代的苄基；或視需要被R 13取代的吡啶基。 Embodiment 8a. The compound as described in formula 1 or any one of the preceding embodiments, wherein R 11 is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 7 alkoxyalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 4 alkylthioalkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl, C 2 -C 4 alkylsulfinylalkyl, C 2 -C 4 alkylsulfonylalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 -C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 -C 5 dialkylaminocarbonyl, C 3 -C 7 alkylaminocarbonylalkyl or C 4 -C 7 dialkylaminocarbonylalkyl; or phenyl optionally substituted by R 13 ; or optionally substituted by R 13 on a ring member benzyl; or pyridyl optionally substituted by R 13 .
實施方式8b. 如實施方式8a所述之化合物，其中R 11係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 2-C 7烷氧基烷基、C 4-C 7環烷基烷基、C 2-C 4烷硫基烷基、C 1-C 4烷基磺醯基、C 1-C 4鹵代烷基磺醯基、C 2-C 4烷基亞磺醯基烷基、C 2-C 4烷基磺醯基烷基、C 2-C 4烷基羰基、C 2-C 4鹵代烷基羰基、C 2-C 5烷氧基羰基、C 3-C 5烷氧基羰基烷基、C 2-C 5烷基胺基羰基、C 3-C 5二烷基胺基羰基、C 3-C 7烷基胺基羰基烷基或C 4-C 7二烷基胺基羰基烷基。 Embodiment 8b. The compound according to embodiment 8a, wherein R 11 is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkane C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 7 alkoxyalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 4 alkylthioalkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl Acyl, C 2 -C 4 Alkylsulfinylalkyl, C 2 -C 4 Alkylsulfonylalkyl, C 2 -C 4 Alkylcarbonyl, C 2 -C 4 Haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 -C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 -C 5 dialkylaminocarbonyl, C 3 -C 7 alkyl Aminocarbonylalkyl or C 4 -C 7 dialkylaminocarbonylalkyl.
實施方式8c. 如實施方式8b所述之化合物，其中R 11係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 2-C 7烷氧基烷基、C 4-C 7環烷基烷基、C 2-C 4烷硫基烷基、C 1-C 4烷基磺醯基、C 1-C 4鹵代烷基磺醯基、C 2-C 4烷基亞磺醯基烷基或C 2-C 4烷基磺醯基烷基。 Embodiment 8c. The compound according to embodiment 8b, wherein R 11 is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkane C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 7 alkoxyalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 4 alkylthioalkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl Acyl, C 2 -C 4 alkylsulfinylalkyl or C 2 -C 4 alkylsulfinylalkyl.
實施方式8d. 如實施方式8c所述之化合物，其中R 11係氫、C 1-C 4烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 4鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 2-C 7烷氧基烷基或C 4-C 7環烷基烷基。 Embodiment 8d. The compound according to embodiment 8c, wherein R 11 is hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkane C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 7 alkoxyalkyl or C 4 -C 7 cycloalkylalkyl.
實施方式8e. 如實施方式8d所述之化合物，其中R 11係氫、C 1-C 4烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基或C 4-C 7環烷基烷基。 Embodiment 8e. The compound according to embodiment 8d, wherein R 11 is hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkane group or C 4 -C 7 cycloalkylalkyl.
實施方式8f. 如實施方式8e所述之化合物，其中R 11係氫、C 1-C 4烷基、C 3-C 6環烷基或C 4-C 7環烷基烷基。 Embodiment 8f. The compound of embodiment 8e, wherein R 11 is hydrogen, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl or C 4 -C 7 cycloalkylalkyl.
實施方式8g. 如實施方式8f所述之化合物，其中R 11係C 1-C 4烷基、C 3-C 6環烷基或C 4-C 7環烷基烷基。 Embodiment 8g. The compound of embodiment 8f, wherein R 11 is C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl or C 4 -C 7 cycloalkylalkyl.
實施方式9a. 如式 1或前述實施方式中任一項所述之化合物，其中R 12係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 2-C 7烷氧基烷基、C 4-C 7環烷基烷基、C 2-C 4烷硫基烷基、C 1-C 4烷基磺醯基、C 1-C 4鹵代烷基磺醯基、C 2-C 4烷基亞磺醯基烷基、C 2-C 4烷基磺醯基烷基、C 2-C 4烷基羰基、C 2-C 4鹵代烷基羰基、C 2-C 5烷氧基羰基、C 3-C 5烷氧基羰基烷基、C 2-C 5烷基胺基羰基、C 3-C 5二烷基胺基羰基、C 3-C 7烷基胺基羰基烷基或C 4-C 7二烷基胺基羰基烷基；或視需要被R 13取代的苯基；或視需要在環成員上被R 13取代的苄基；或視需要被R 13取代的吡啶基。 Embodiment 9a. The compound as described in formula 1 or any one of the preceding embodiments, wherein R 12 is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 7 alkoxyalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 4 alkylthioalkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl, C 2 -C 4 alkylsulfinylalkyl, C 2 -C 4 alkylsulfonylalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 -C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 -C 5 dialkylaminocarbonyl, C 3 -C 7 alkylaminocarbonylalkyl or C 4 -C 7 dialkylaminocarbonylalkyl; or phenyl optionally substituted by R 13 ; or optionally substituted by R 13 on a ring member benzyl; or pyridyl optionally substituted by R 13 .
實施方式9b. 如實施方式9a所述之化合物，其中R 12係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 2-C 4鹵代烯基、C 2-C 4鹵代炔基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 2-C 7烷氧基烷基、C 4-C 7環烷基烷基、C 2-C 4烷硫基烷基、C 1-C 4烷基磺醯基、C 1-C 4鹵代烷基磺醯基、C 2-C 4烷基亞磺醯基烷基、C 2-C 4烷基磺醯基烷基、C 2-C 4烷基羰基、C 2-C 4鹵代烷基羰基、C 2-C 5烷氧基羰基、C 3-C 5烷氧基羰基烷基、C 2-C 5烷基胺基羰基、C 3-C 5二烷基胺基羰基、C 3-C 7烷基胺基羰基烷基或C 4-C 7二烷基胺基羰基烷基。 Embodiment 9b. The compound according to embodiment 9a, wherein R 12 is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkane C 1 -C 6 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 7 alkoxyalkyl, C 4 -C 7 cycloalkylalkyl, C 2 -C 4 alkylthioalkyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl Acyl, C 2 -C 4 Alkylsulfinylalkyl, C 2 -C 4 Alkylsulfonylalkyl, C 2 -C 4 Alkylcarbonyl, C 2 -C 4 Haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 -C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 -C 5 dialkylaminocarbonyl, C 3 -C 7 alkyl Aminocarbonylalkyl or C 4 -C 7 dialkylaminocarbonylalkyl.
實施方式9c. 如實施方式9b所述之化合物，其中R 12係氫、C 1-C 6烷基、C 2-C 4烯基、C 2-C 4炔基、C 3-C 6環烷基、C 1-C 6鹵代烷基、C 4-C 7環烷基烷基、C 1-C 4烷基磺醯基、C 2-C 4烷基羰基或C 2-C 5烷氧基羰基。 Embodiment 9c. The compound according to embodiment 9b, wherein R 12 is hydrogen, C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkane C 1 -C 6 haloalkyl, C 4 -C 7 cycloalkylalkyl, C 1 -C 4 alkylsulfonyl, C 2 -C 4 alkylcarbonyl or C 2 -C 5 alkoxycarbonyl .
實施方式9d. 如實施方式9c所述之化合物，其中R 12係氫、C 1-C 4烷基、C 2-C 4烷基羰基或C 2-C 5烷氧基羰基。 Embodiment 9d. The compound of embodiment 9c, wherein R 12 is hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkylcarbonyl or C 2 -C 5 alkoxycarbonyl.
實施方式9e. 如實施方式9c所述之化合物，其中R 12係C 1-C 4烷基、C 2-C 4烷基羰基或C 2-C 5烷氧基羰基。 Embodiment 9e. The compound of embodiment 9c, wherein R 12 is C 1 -C 4 alkyl, C 2 -C 4 alkylcarbonyl or C 2 -C 5 alkoxycarbonyl.
實施方式9f. 如實施方式9c所述之化合物，其中R 12係氫、C 2-C 4烷基羰基或C 2-C 5烷氧基羰基。 Embodiment 9f. The compound of embodiment 9c, wherein R 12 is hydrogen, C 2 -C 4 alkylcarbonyl or C 2 -C 5 alkoxycarbonyl.
實施方式10a. 如式 1或前述實施方式中任一項所述之化合物，其中R 11和R 12連同它們所附接的氮一起形成3員至6員環，該環含有選自碳原子和最多兩個獨立地選自氮、硫和氧的另外原子的環成員，所述環視需要被1至2個獨立地選自以下各項的取代基取代：鹵素、C 1-C 2烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基、氰基和硝基。 Embodiment 10a. The compound as described in formula 1 or any one of the preceding embodiments, wherein R 11 and R 12 together with the nitrogen to which they are attached form a 3- to 6-membered ring containing carbon atoms and Up to two ring members of additional atoms independently selected from nitrogen, sulfur and oxygen, optionally substituted with 1 to 2 substituents independently selected from the group consisting of halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro.
實施方式10b. 如實施方式10a所述之化合物，其中R 11和R 12連同它們所附接的氮一起形成3員至6員環，該環含有選自碳原子和最多兩個獨立地選自氮、硫和氧的另外原子的環成員，所述環視需要被1至2個獨立地選自以下各項的取代基取代：鹵素、C 1-C 2烷基和C 1-C 2鹵代烷基。 Embodiment 10b. The compound according to embodiment 10a, wherein R 11 and R 12 together with the nitrogen to which they are attached form a 3 to 6 member ring containing carbon atoms and up to two independently selected from Ring members of additional atoms of nitrogen, sulfur and oxygen, which are optionally substituted with 1 to 2 substituents independently selected from the group consisting of halogen, C 1 -C 2 alkyl and C 1 -C 2 haloalkyl .
實施方式10c. 如實施方式10b所述之化合物，其中R 11和R 12連同它們所附接的氮一起形成3員至5員環，該環含有選自碳原子和最多一個獨立地選自氮、硫和氧的另外原子的環成員，所述環視需要被1至2個獨立地選自以下各項的取代基取代：鹵素、C 1-C 2烷基和C 1-C 2鹵代烷基。 Embodiment 10c. The compound of embodiment 10b, wherein R 11 and R 12 together with the nitrogen to which they are attached form a 3- to 5-membered ring containing atoms selected from carbon atoms and at most one atom independently selected from nitrogen A ring member of another atom of , sulfur and oxygen, said ring needs to be substituted with 1 to 2 substituents independently selected from the group consisting of halogen, C 1 -C 2 alkyl and C 1 -C 2 haloalkyl.
實施方式11a. 如式 1或前述實施方式中任一項所述之化合物，其中R 13係鹵素、C 1-C 3烷基、C 1-C 3鹵代烷基、C 1-C 3烷氧基或C 1-C 3鹵代烷氧基。 Embodiment 11a. The compound as described in formula 1 or any one of the preceding embodiments, wherein R 13 is halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy or C 1 -C 3 haloalkoxy.
實施方式11b. 如實施方式11a所述之化合物，其中R 13係鹵素、C 1-C 3烷基、C 1-C 3鹵代烷基。 Embodiment 11b. The compound according to embodiment 11a, wherein R 13 is halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl.
實施方式11c. 如實施方式11b所述之化合物，其中R 13係鹵素。 Embodiment 11c. The compound of embodiment 11b, wherein R 13 is halogen.
實施方式12a. 如式 1或前述實施方式中任一項所述之化合物，其中J係苯基或萘基，每個環或環系統視需要被最多4個獨立地選自R JC的取代基取代；或5員或6員雜環或者8員、9員或10員二環系統，每個環或環系統含有選自碳原子和1至3個雜原子的環成員，該等雜原子獨立地選自最多1個硼、最多2個氧、最多1個硫和最多3個氮原子，其中最多1個碳環成員視需要選自C(=O)和C(=S)，每個環系統視需要被最多4個取代基取代，該等取代基獨立地選自碳原子環成員上的R JC、氮原子環成員上的R JN和硼原子環成員上的R JB。 Embodiment 12a. The compound as described in formula 1 or any one of the preceding embodiments, wherein J is phenyl or naphthyl, and each ring or ring system is optionally up to 4 substituents independently selected from R J C Substituted; or a 5- or 6-membered heterocyclic ring or an 8-, 9- or 10-membered bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and 1 to 3 heteroatoms, independently selected from up to 1 boron, up to 2 oxygen, up to 1 sulfur and up to 3 nitrogen atoms, with up to 1 carbon ring member optionally selected from C(=O) and C(=S), each ring The system is optionally substituted with up to 4 substituents independently selected from R JC on carbon atom ring members, R JN on nitrogen atom ring members and R JB on boron atom ring members.
實施方式12b. 如實施方式12a所述之化合物，其中J係苯基或萘基，每個環視需要被最多4個獨立地選自R JC的取代基取代；或5員或6員雜環，每個環含有選自碳原子和1至3個雜原子的環成員，該等雜原子獨立地選自最多2個氧、最多1個硫和最多3個氮原子，其中最多1個碳環成員視需要選自C(=O)和C(=S)，每個環系統視需要被最多4個取代基取代，該等取代基獨立地選自碳原子環成員上的R JC和氮原子環成員上的R JN。 Embodiment 12b. The compound as described in Embodiment 12a, wherein J is phenyl or naphthyl, and each ring is optionally substituted by up to 4 substituents independently selected from R JC ; or a 5-membered or 6-membered heterocycle, Each ring contains ring members selected from carbon atoms and 1 to 3 heteroatoms independently selected from up to 2 oxygen, up to 1 sulfur and up to 3 nitrogen atoms, of which up to 1 is a carbon ring member Optionally selected from C(=O) and C(=S), each ring system optionally substituted with up to 4 substituents independently selected from R JC on carbon atom ring members and nitrogen atom ring R JN on member.
實施方式12c. 如式 1或前述實施方式中任一項所述之化合物，其中J選自如示例1中所示的U-1至U-61，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2、3或4。 Embodiment 12c. The compound of Formula 1 or any one of the preceding embodiments, wherein J is selected from U-1 to U-61 as shown in Example 1, wherein at most 1 carbocyclic member is optionally selected from C (=0); and when R v is attached to a carbon ring member, said R v is selected from R JC , and when R v is attached to a nitrogen ring member, said R v is selected from R JN ; and r is 0, 1, 2, 3 or 4.
實施方式12d. 如實施方式12c所述之化合物，其中J選自U-2至U-61。Embodiment 12d. The compound of embodiment 12c, wherein J is selected from U-2 to U-61.
實施方式12d1. 如實施方式12c所述之化合物，其中J選自U-49至U-61。Embodiment 12d1. The compound of embodiment 12c, wherein J is selected from U-49 to U-61.
實施方式12d2. 如實施方式12c所述之化合物，其中J選自U-49至U-61，其中1個碳環成員係C(=O)。Embodiment 12d2. The compound of embodiment 12c, wherein J is selected from U-49 to U-61, wherein one carbocyclic member is C(=O).
實施方式12e. 如實施方式12c所述之化合物，其中J選自U-1、U-2、U-4、U-26、U-28、U-37、U-38、U-39、U-49、U-50、U-51、U-53或U-56。Embodiment 12e. The compound as described in embodiment 12c, wherein J is selected from U-1, U-2, U-4, U-26, U-28, U-37, U-38, U-39, U -49, U-50, U-51, U-53 or U-56.
實施方式12f. 如式 1或前述實施方式中任一項所述之化合物，其中J選自U-1、U-2、U-4、U-26、U-37、U-38、U-39、U-49、U-50或U-51。 Embodiment 12f. The compound of formula 1 or any one of the preceding embodiments, wherein J is selected from U-1, U-2, U-4, U-26, U-37, U-38, U- 39. U-49, U-50 or U-51.
實施方式12g. 如式 1或前述實施方式中任一項所述之化合物，其中J選自U-1或U-26；或U-50，其中最多1個碳環成員視需要選自C(=O)。 Embodiment 12g. The compound of Formula 1 or any one of the preceding embodiments, wherein J is selected from U-1 or U-26; or U-50, wherein up to 1 carbocyclic member is optionally selected from C( =O).
實施方式12h. 如實施方式12g所述之化合物，其中J係U-1。Embodiment 12h. The compound of embodiment 12g, wherein J is U-1.
實施方式12i. 如實施方式12g所述之化合物，其中J係U-26。Embodiment 12i. The compound of embodiment 12g, wherein J is U-26.
實施方式12j. 如實施方式12g所述之化合物，其中J係U-50。Embodiment 12j. The compound of embodiment 12g, wherein J is U-50.
實施方式12k. 如實施方式12g所述之化合物，其中J係U-50，其中1個碳環成員係C(=O)。Embodiment 12k. The compound of embodiment 12g, wherein J is U-50, and one of the carbocyclic members is C(=O).
實施方式13. 如式 1或實施方式1至12a中任一項所述之化合物，其中J選自如示例3中所示的U-81至U-124，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2、3或4。 Embodiment 13. The compound as described in any one of Formula 1 or Embodiments 1 to 12a, wherein J is selected from U-81 to U-124 as shown in Example 3, wherein at most 1 carbon ring member is optionally selected from C(=O); and when Rv is attached to a carbon ring member, said Rv is selected from RJC , and when Rv is attached to a nitrogen ring member, said Rv is selected from RJN ; and r is 0, 1, 2, 3 or 4.
實施方式13a. 如實施方式13所述之化合物，其中J選自U-90至U-96、U-105、U-110或U-117至U-124。Embodiment 13a. The compound of embodiment 13, wherein J is selected from U-90 to U-96, U-105, U-110 or U-117 to U-124.
實施方式13b. 如實施方式13所述之化合物，其中J係U-105。Embodiment 13b. The compound of embodiment 13, wherein J is U-105.
實施方式13c. 如實施方式13所述之化合物，其中J選自U-91、U-94、U-95、U-96、U-110、U-117、U-118或U-124。Embodiment 13c. The compound of embodiment 13, wherein J is selected from U-91, U-94, U-95, U-96, U-110, U-117, U-118 or U-124.
實施方式13d. 如實施方式13所述之化合物，其中J選自U-91。Embodiment 13d. The compound of embodiment 13, wherein J is selected from U-91.
實施方式14a. 如式 1或前述實施方式中任一項所述之化合物，其中r係1或2。 Embodiment 14a. A compound of Formula 1 or any one of the preceding embodiments, wherein r is 1 or 2.
實施方式14b. 如實施方式14a所述之化合物，其中r係1。Embodiment 14b. The compound of embodiment 14a, wherein r is 1.
實施方式14c. 如實施方式14a所述之化合物，其中r係2。Embodiment 14c. The compound of embodiment 14a, wherein r is 2.
實施方式14d. 如式 1或實施方式1至13d中任一項所述之化合物，其中r係3。 Embodiment 14d. The compound of Formula 1 or any one of Embodiments 1 to 13d, wherein r is 3.
實施方式14d. 如式 1或實施方式1至13d中任一項所述之化合物，其中r係4。 Embodiment 14d. The compound of Formula 1 or any one of Embodiments 1 to 13d, wherein r is 4.
實施方式15a. 如式 1或前述實施方式中任一項所述之化合物，其中每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、硝基、OR 14、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2。 Embodiment 15a. A compound of Formula 1 or any one of the preceding embodiments, wherein each R JC is independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 - C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the following : Halogen, cyano, nitro, OR 14 , C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 .
實施方式15b. 如實施方式15a所述之化合物，其中每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18或S(=O) nR 21。 Embodiment 15b. The compound of Embodiment 15a, wherein each R JC is independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C (=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl, C 2 -C 6 alkene C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, C(=O) R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 or S(=O) n R 21 .
實施方式15c. 如實施方式15b所述之化合物，其中每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18或S(=O) nR 21。 Embodiment 15c. The compound of Embodiment 15b, wherein each R JC is independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C (=Z) NR 17 R 18 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally replaced by one or a plurality of substituents independently selected from the following: halogen, cyano, CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 or S(= O) n R 21 .
實施方式15d. 如實施方式15c所述之化合物，其中每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)OR 16或C(=Z)NR 17R 18。 Embodiment 15d. The compound of Embodiment 15c, wherein each R JC is independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C (=Z) NR 17 R 18 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally replaced by one or multiple substituents independently selected from the group consisting of halogen, cyano, C(=O)OR 16 or C(=Z)NR 17 R 18 .
實施方式16a. 如式 1或前述實施方式中任一項所述之化合物，其中每個R JN獨立地是氫、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18或S(=O) nR 21。 Embodiment 16a. A compound of Formula 1 or any one of the preceding embodiments, wherein each R JN is independently hydrogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O )OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 or S(=O) n R 21 .
實施方式16b. 如實施方式16a所述之化合物，其中每個R JN獨立地是氫、羥基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18或S(=O) nR 21。 Embodiment 16b. The compound of Embodiment 16a, wherein each R JN is independently hydrogen, hydroxyl, OR 14 , C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally replaced by one or more independently Substitution with a substituent selected from the group consisting of halogen, cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 or S(=O) n R 21 .
實施方式16c. 如實施方式16b所述之化合物，其中每個R JN獨立地是氫、羥基、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16或C(=Z)NR 17R 18。 Embodiment 16c. The compound of Embodiment 16b, wherein each R JN is independently hydrogen, hydroxyl, C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the group consisting of halogen, Cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 or C(=Z)NR 17 R 18 .
實施方式16d. 如實施方式16c所述之化合物，其中每個R JN獨立地是氫、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18或NR 17R 18；或C 1-C 6烷基，其視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、C(=O)OR 16或C(=Z)NR 17R 18。 Embodiment 16d. A compound according to Embodiment 16c, wherein each R JN is independently hydrogen, C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 or NR 17 R 18 ; or C 1 -C 6 alkyl, optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, C(=O)R 15 , C(=O )OR 16 or C(=Z)NR 17 R 18 .
實施方式17. 如式 1或前述實施方式中任一項所述之化合物，其中每個R JB獨立地是羥基或C 1-C 6烷氧基。 Embodiment 17. The compound of Formula 1 or any one of the preceding embodiments, wherein each R JB is independently hydroxyl or C 1 -C 6 alkoxy.
實施方式18a. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 14獨立地是C 1-C 6烷基、C 3-C 7環烷基、C 1-C 6鹵代烷基或C 3-C 7鹵代環烷基。 Embodiment 18a. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 14 is independently C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 Haloalkyl or C 3 -C 7 halocycloalkyl.
實施方式18a1. 如實施方式18a所述之化合物，其中每個R 14獨立地是C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基或C 3-C 6鹵代環烷基。 Embodiment 18a1. The compound of embodiment 18a, wherein each R 14 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl or C 3 -C 6 halocycloalkyl.
實施方式18a2. 如實施方式18a1所述之化合物，其中每個R 14獨立地是C 1-C 4烷基、C 3-C 6環烷基或C 1-C 4鹵代烷基。 Embodiment 18a2. The compound of embodiment 18a1, wherein each R 14 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 1 -C 4 haloalkyl.
實施方式18b. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 15獨立地是C 1-C 6烷基、C 3-C 7環烷基、C 1-C 6鹵代烷基或C 3-C 6鹵代環烷基。 Embodiment 18b. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 15 is independently C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 Haloalkyl or C 3 -C 6 halocycloalkyl.
實施方式18b1. 如實施方式18b所述之化合物，其中每個R 15獨立地是C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基或C 3-C 6鹵代環烷基。 Embodiment 18b1. The compound of embodiment 18b, wherein each R 15 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, or C 3 -C 6 halocycloalkyl.
實施方式18b2. 如實施方式18b1所述之化合物，其中每個R 15獨立地是C 1-C 4烷基、C 3-C 6環烷基或C 1-C 4鹵代烷基。 Embodiment 18b2. The compound of embodiment 18b1, wherein each R 15 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 1 -C 4 haloalkyl.
實施方式18c. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 16獨立地是C 1-C 6烷基、C 3-C 7環烷基或C 1-C 6鹵代烷基。 Embodiment 18c. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 16 is independently C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, or C 1 -C 6 Haloalkyl.
實施方式18c1. 如實施方式18c所述之化合物，其中每個R 16獨立地是C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基或C 3-C 6鹵代環烷基。 Embodiment 18c1. The compound of embodiment 18c, wherein each R 16 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, or C 3 -C 6 halocycloalkyl.
實施方式18c2. 如實施方式18c1所述之化合物，其中每個R 16獨立地是C 1-C 4烷基、C 3-C 6環烷基或C 1-C 4鹵代烷基。 Embodiment 18c2. The compound of embodiment 18c1, wherein each R 16 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 1 -C 4 haloalkyl.
實施方式18d1. 如式 1或前述實施方式中任一項所述之化合物，其中Z係O。 Embodiment 18d1. The compound of Formula 1 or any one of the preceding embodiments, wherein Z is O.
實施方式18d2. 如式 1或實施方式1至18c2中任一項所述之化合物，其中Z係S。 Embodiment 18d2. The compound of Formula 1 or any one of Embodiments 1 to 18c2, wherein Z is S.
實施方式19. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 17獨立地是氫、羥基、OR 22、C(=O)R 23、C(=O)OR 24、C(=O)NR 25R 26、NR 25R 26或S(=O) nR 21；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 19. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 17 is independently hydrogen, hydroxyl, OR 22 , C(=O)R 23 , C(=O)OR 24 , C(=O)NR 25 R 26 , NR 25 R 26 or S(=O) n R 21 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally replaced by 1 to Substituted by 3 substituents independently selected from Rx .
實施方式19a. 如實施方式19所述之化合物，其中每個R 17獨立地是氫、C(=O)R 23、C(=O)OR 24、C(=O)NR 25R 26或S(=O) nR 21；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 19a. The compound of embodiment 19, wherein each R 17 is independently hydrogen, C(=O)R 23 , C(=O)OR 24 , C(=O)NR 25 R 26 or S (=O) n R 21 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally substituted by 1 to 3 substituents independently selected from R x .
實施方式19b. 如實施方式19a所述之化合物，其中每個R 17獨立地是氫、C(=O)R 23、C(=O)OR 24或C(=O)NR 25R 26；或C 1-C 4烷基，其視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 19b. The compound of embodiment 19a, wherein each R 17 is independently hydrogen, C(=O)R 23 , C(=O)OR 24 or C(=O)NR 25 R 26 ; or C 1 -C 4 alkyl, optionally substituted with 1 to 3 substituents independently selected from R x .
實施方式19c. 如實施方式19a所述之化合物，其中每個R 17獨立地是氫、C(=O)R 23、C(=O)OR 24或C(=O)NR 25R 26；或C 1-C 4烷基或C 3-C 5環烷基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 19c. The compound of embodiment 19a, wherein each R 17 is independently hydrogen, C(=O)R 23 , C(=O)OR 24 or C(=O)NR 25 R 26 ; or C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected from R x .
實施方式19d. 如實施方式19c所述之化合物，其中每個R 17獨立地是氫；或C 1-C 4烷基或C 3-C 5環烷基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 19d. The compound of embodiment 19c, wherein each R 17 is independently hydrogen; or C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl, each optionally replaced by 1 to 3 Substituents independently selected from Rx are substituted.
實施方式19e. 如實施方式19d所述之化合物，其中每個R 17獨立地是C 1-C 4烷基或C 3-C 5環烷基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 19e. The compound of embodiment 19d, wherein each R 17 is independently C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl, each optionally selected from 1 to 3 independently Substituents from Rx .
實施方式20. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 18獨立地是氫或Q 2；或C 1-C 6烷基、C 3-C 7環烷基、C 2-C 7烷基羰基或C 2-C 7烷氧基羰基，每個視需要被R x取代。 Embodiment 20. The compound of formula 1 or any one of the preceding embodiments, wherein each R 18 is independently hydrogen or Q 2 ; or C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl , C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl, each optionally substituted by R x .
實施方式20a. 如實施方式20所述之化合物，其中每個R 18獨立地是氫；或C 1-C 6烷基、C 3-C 7環烷基、C 2-C 7烷基羰基或C 2-C 7烷氧基羰基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment 20a. The compound of embodiment 20, wherein each R 18 is independently hydrogen; or C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxycarbonyl, each optionally substituted with 1 to 3 substituents independently selected from R x .
實施方式20b. 如實施方式20a所述之化合物，其中每個R 18獨立地是氫、C 1-C 4烷基、C 3-C 5環烷基、C 2-C 5烷基羰基或C 2-C 5烷氧基羰基。 Embodiment 20b. The compound of embodiment 20a, wherein each R 18 is independently hydrogen, C 1 -C 4 alkyl, C 3 -C 5 cycloalkyl, C 2 -C 5 alkylcarbonyl, or C 2 -C 5 alkoxycarbonyl.
實施方式20c. 如實施方式20b所述之化合物，其中每個R 18獨立地是氫或C 1-C 4烷基。 Embodiment 20c. The compound of embodiment 20b, wherein each R 18 is independently hydrogen or C 1 -C 4 alkyl.
實施方式20d. 如實施方式20c所述之化合物，其中R 18係氫。 Embodiment 20d. The compound of embodiment 20c, wherein R 18 is hydrogen.
實施方式21a. 如式 1或前述實施方式中任一項所述之化合物，其中R 17和R 18連同它們所附接的氮一起形成3員至5員環，該環含有選自碳原子和最多兩個獨立地選自氮、硫和氧的另外原子的環成員，其中硫原子環成員選自S、S(=O)和S(=O) 2，所述環視需要被1至3個獨立地選自以下各項的取代基取代：鹵素、C 1-C 2烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基、氰基和硝基。 Embodiment 21a. The compound of Formula 1 or any one of the preceding embodiments, wherein R 17 and R 18 together with the nitrogen to which they are attached form a 3- to 5-membered ring containing atoms selected from carbon atoms and Up to two additional atom ring members independently selected from nitrogen, sulfur and oxygen, wherein the sulfur atom ring member is selected from S, S(=O) and S(=O) 2 , the ring needs to be replaced by 1 to 3 Substituents independently selected from the group consisting of halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro.
實施方式21b. 如式 1或前述實施方式中任一項所述之化合物，其中R 17和R 18一起形成為=S(=O) uR 27R 28。 Embodiment 21b. A compound of Formula 1 or any one of the preceding embodiments, wherein R 17 and R 18 are taken together to form =S(=O) u R 27 R 28 .
實施方式21c. 如式 1或前述實施方式中任一項所述之化合物，其中R 17和R 18一起形成為=S(=NR 29)R 27R 28。 Embodiment 21c. A compound of Formula 1 or any one of the preceding embodiments, wherein R 17 and R 18 are taken together to form =S(=NR 29 )R 27 R 28 .
實施方式22. 如式 1或前述實施方式中任一項所述之化合物，其中每個R x獨立地是鹵素、氰基、C 1-C 6烷基、C 1-C 6鹵代烷基、C 3-C 6環烷基、C 1-C 6烷氧基、C 1-C 6鹵代烷氧基、C 3-C 6環烷氧基、OC(=O)R 23、C(=O)R 23、C(=O)OR 24、C(=O)NR 25R 26、C(=NR 19)R 25、NR 25R 26、S(=O) nR 30、Si(R 31) 3、OSi(R 31) 3或Q 2。 Embodiment 22. The compound of Formula 1 or any one of the preceding embodiments, wherein each R x is independently halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 6 cycloalkoxy, OC(=O)R 23 , C(=O)R 23 , C(=O)OR 24 , C(=O)NR 25 R 26 , C(=NR 19 )R 25 , NR 25 R 26 , S(=O) n R 30 , Si(R 31 ) 3 , OSi(R 31 ) 3 or Q 2 .
實施方式22a. 如實施方式22所述之化合物，其中每個R x獨立地是鹵素、氰基、C 1-C 6烷基、C 1-C 6鹵代烷基、C 3-C 6環烷基、C 1-C 6烷氧基、C 1-C 6鹵代烷氧基、C 3-C 6環烷氧基、OC(=O)R 23、C(=O)R 23、C(=O)OR 24、C(=O)NR 25R 26、NR 25R 26或S(=O) nR 30。 Embodiment 22a. The compound of Embodiment 22, wherein each R x is independently halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl , C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 6 cycloalkoxy, OC(=O)R 23 , C(=O)R 23 , C(=O) OR 24 , C(=O)NR 25 R 26 , NR 25 R 26 or S(=O) nR 30 .
實施方式22b. 如實施方式22a所述之化合物，其中每個R x獨立地是鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 3-C 5環烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C(=O)R 23、C(=O)OR 24、C(=O)NR 25R 26、NR 25R 26或S(=O) nR 30。 Embodiment 22b. The compound of embodiment 22a, wherein each R x is independently halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 5 cycloalkyl , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C(=O)R 23 , C(=O)OR 24 , C(=O)NR 25 R 26 , NR 25 R 26 or S(=O) n R 30 .
實施方式22c. 如實施方式22b所述之化合物，其中每個R x獨立地是鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 3-C 5環烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C(=O)R 23、C(=O)OR 24或C(=O)NR 25R 26。 Embodiment 22c. The compound of embodiment 22b, wherein each R x is independently halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 5 cycloalkyl , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C(=O)R 23 , C(=O)OR 24 or C(=O)NR 25 R 26 .
實施方式22d. 如實施方式22c所述之化合物，其中每個R x獨立地是鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基。 Embodiment 22d. The compound of embodiment 22c, wherein each R x is independently halogen, C 1 -C 4 alkyl, or C 1 -C 4 haloalkyl.
實施方式23. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 19獨立地是OR 22或NHR 32。 Embodiment 23. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 19 is independently OR 22 or NHR 32 .
實施方式24. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 20獨立地是氫；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被1至3個R x取代。 Embodiment 24. The compound of formula 1 or any one of the preceding embodiments, wherein each R 20 is independently hydrogen; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each Optionally replaced by 1 to 3 Rx .
實施方式25. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 21獨立地是胺基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 3-C 6環烷基或苯基。 Embodiment 25. The compound of formula 1 or any one of the preceding embodiments, wherein each R 21 is independently amino, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 - C 6 cycloalkyl or phenyl.
實施方式26. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 22獨立地是C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基或Q 2。 Embodiment 26. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 22 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 Haloalkyl or Q 2 .
實施方式26a. 如實施方式26所述之化合物，其中每個R 22獨立地是C 1-C 4烷基、C 3-C 6環烷基或C 1-C 4鹵代烷基。 Embodiment 26a. The compound of embodiment 26, wherein each R 22 is independently C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 1 -C 4 haloalkyl.
實施方式26b. 如實施方式26a所述之化合物，其中每個R 22獨立地是C 1-C 4烷基。 Embodiment 26b. The compound of embodiment 26a, wherein each R 22 is independently C 1 -C 4 alkyl.
實施方式27. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 23獨立地是C 1-C 4烷基、C 1-C 4鹵代烷基、C 3-C 6環烷基、C 3-C 6鹵代環烷基、C 4-C 7環烷基烷基或C 4-C 7鹵代環烷基烷基。 Embodiment 27. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 23 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 ring Alkyl, C 3 -C 6 halocycloalkyl, C 4 -C 7 cycloalkylalkyl or C 4 -C 7 halocycloalkylalkyl.
實施方式27a. 如實施方式27所述之化合物，其中每個R 23獨立地是C 1-C 4烷基、C 1-C 4鹵代烷基、C 3-C 6環烷基或C 3-C 6鹵代環烷基。 Embodiment 27a. The compound of embodiment 27, wherein each R 23 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl, or C 3 -C 6 halocycloalkyl.
實施方式27b. 如實施方式27a所述之化合物，其中每個R 23獨立地是C 1-C 4烷基、C 1-C 4鹵代烷基或C 3-C 6環烷基。 Embodiment 27b. The compound of embodiment 27a, wherein each R 23 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 3 -C 6 cycloalkyl.
實施方式28. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 24獨立地是C 1-C 4烷基、C 1-C 4鹵代烷基、C 3-C 6環烷基或C 3-C 6鹵代環烷基。 Embodiment 28. The compound of formula 1 or any one of the preceding embodiments, wherein each R 24 is independently C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 ring Alkyl or C 3 -C 6 halocycloalkyl.
實施方式29. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 25獨立地是氫、C 1-C 6烷基、C 1-C 6鹵代烷基、C(=O)R 33或S(=O) nR 33。 Embodiment 29. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 25 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C(=O )R 33 or S(=O) n R 33 .
實施方式30. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 26獨立地是氫或C 1-C 6烷基。 Embodiment 30. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 26 is independently hydrogen or C 1 -C 6 alkyl.
實施方式31. 如式 1或前述實施方式中任一項所述之化合物，其中R 25和R 26連同它們所附接的氮原子一起形成3員至6員環，該環含有選自碳原子和最多2個雜原子的環成員，該等雜原子獨立地選自一個氧原子、一個硫原子和最多2個氮原子，所述環視需要被1至3個獨立地選自以下群組的取代基取代，該群組由以下各項組成：鹵素、氰基、C 1-C 4烷基、C 3-C 6環烷基和C 1-C 4鹵代烷基。 Embodiment 31. The compound of formula 1 or any one of the preceding embodiments, wherein R 25 and R 26 together with the nitrogen atom to which they are attached form a 3- to 6-membered ring containing carbon atoms selected from and ring members of up to 2 heteroatoms independently selected from one oxygen atom, one sulfur atom and up to 2 nitrogen atoms, said ring being optionally substituted with 1 to 3 members independently selected from the group substituent, the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl and C 1 -C 4 haloalkyl.
實施方式32. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 27獨立地是C 1-C 4烷基或C 1-C 4鹵代烷基。 Embodiment 32. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 27 is independently C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
實施方式33. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 28獨立地是C 1-C 4烷基或C 1-C 4鹵代烷基。 Embodiment 33. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 28 is independently C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.
實施方式34. 如式 1或前述實施方式中任一項所述之化合物，其中每個R 29獨立地是氫、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基或C(=O)R 23。 Embodiment 34. The compound of Formula 1 or any one of the preceding embodiments, wherein each R 29 is independently hydrogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C (=O)R 23 .
實施方式34a. 如實施方式34所述之化合物，其中每個R 29獨立地是氫或C 1-C 4烷基。 Embodiment 34a. The compound of embodiment 34, wherein each R 29 is independently hydrogen or C 1 -C 4 alkyl.
實施方式35. 如式 1或前述實施方式中任一項所述之化合物，其中每個Q 2獨立地是苯基，其視需要被一個或多個獨立地選自以下群組的取代基取代，該群組由以下各項組成：鹵素、氰基、C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基和C 1-C 4鹵代烷氧基；或5員或6員雜環芳族環，每個環含有選自碳原子和最多2個雜原子的環成員，該等雜原子獨立地選自一個氧原子、一個硫原子和最多2個氮原子，每個環視需要被一個或多個獨立地選自以下群組的取代基取代，該群組由以下各項組成：鹵素、氰基、C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基和C 1-C 4鹵代烷氧基。 Embodiment 35. The compound of formula 1 or any one of the preceding embodiments, wherein each Q is independently phenyl, optionally substituted by one or more substituents independently selected from the following groups , the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 - C4haloalkoxy ; or a 5-membered or 6-membered heterocyclic aromatic ring, each ring containing ring members selected from carbon atoms and up to 2 heteroatoms independently selected from an oxygen atom, A sulfur atom and up to 2 nitrogen atoms, each ring needs to be substituted by one or more substituents independently selected from the group consisting of: halogen, cyano, C 1 -C 4 Alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy.
實施方式35a. 如式 1或前述實施方式中任一項所述之化合物，其中每個Q 2獨立地是苯基，其視需要被一個或多個獨立地選自以下群組的取代基取代，該群組由以下各項組成：鹵素、氰基、C 1-C 4烷基、C 3-C 6環烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基和C 1-C 4鹵代烷氧基。 Embodiment 35a. The compound of Formula 1 or any one of the preceding embodiments, wherein each Q is independently phenyl, optionally substituted with one or more substituents independently selected from the following groups , the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy.
實施方式36a. 如式 1或前述實施方式中任一項所述之化合物，其中n係0。 Embodiment 36a. The compound of Formula 1 or any one of the preceding embodiments, wherein n is zero.
實施方式36b. 如式 1或實施方式1至35中任一項所述之化合物，其中n係1或2。 Embodiment 36b. The compound of Formula 1 or any one of Embodiments 1-35, wherein n is 1 or 2.
實施方式36c. 如實施方式36b所述之化合物，其中n係1。Embodiment 36c. The compound of embodiment 36b, wherein n is 1.
實施方式36d. 如實施方式36b所述之化合物，其中n係2。Embodiment 36d. The compound of embodiment 36b, wherein n is 2.
實施方式37a. 如式 1或前述實施方式中任一項所述之化合物，其中u係0。 Embodiment 37a. The compound of Formula 1 or any one of the preceding embodiments, wherein u is 0.
實施方式37b. 如式 1或實施方式1至36d中任一項所述之化合物，其中u係1。 Embodiment 37b. The compound of Formula 1 or any one of Embodiments 1 to 36d, wherein u is 1.
實施方式S1. 如實施方式1-37b中任一項所述之化合物，其中該式 1的化合物係式 1 i 的化合物。 Embodiment S1. The compound according to any one of embodiments 1-37b, wherein the compound of formula 1 is a compound of formula 1i .
實施方式S2. 如實施方式1-37b中任一項所述之化合物，其中該式 1的化合物係式 1 ii 的化合物。 Embodiment S2. The compound according to any one of embodiments 1-37b, wherein the compound of formula 1 is a compound of formula ii .
實施方式S3. 一種由式 1 i 的化合物和式 1 ii 的化合物組成的組成物，其中該式 1 i 的化合物與該式 1 ii 的化合物的比率大於60 : 40。 Embodiment S3. A composition consisting of a compound of formula 1 i and a compound of formula 1 ii , wherein the ratio of the compound of formula 1 i to the compound of formula 1 ii is greater than 60:40.
實施方式S3a. 如實施方式S3所述之組成物，其中該式 1 i 的化合物與該式 1 ii 的化合物的比率大於80 : 20。 Embodiment S3a. The composition as described in embodiment S3, wherein the ratio of the compound of formula 1 i to the compound of formula 1 ii is greater than 80:20.
實施方式S3b. 如實施方式S3所述之組成物，其中該式 1 i 的化合物與該式 1 ii 的化合物的比率大於90 : 10。 Embodiment S3b. The composition as described in embodiment S3, wherein the ratio of the compound of formula 1 i to the compound of formula 1 ii is greater than 90:10.
實施方式S3c. 如實施方式S3所述之組成物，其中該式 1 i 的化合物與該式 1 ii 的化合物的比率大於99 : 1。 Embodiment S3c. The composition as described in embodiment S3, wherein the ratio of the compound of formula 1 i to the compound of formula 1 ii is greater than 99:1.
實施方式S4. 一種由式 1 ii 的化合物和式 1 i 的化合物組成的組成物，其中該式 1 ii 的化合物與該式 1 i 的化合物的比率大於60 : 40。 Embodiment S4. A composition consisting of a compound of formula 1 ii and a compound of formula 1 i , wherein the ratio of the compound of formula 1 ii to the compound of formula 1 i is greater than 60:40.
實施方式S4a. 如實施方式S4所述之組成物，其中該式 1 ii 的化合物與該式 1 i 的化合物的比率大於80 : 20。 Embodiment S4a. The composition as described in embodiment S4, wherein the ratio of the compound of formula 1 ii to the compound of formula 1 i is greater than 80:20.
實施方式S4b. 如實施方式S4所述之組成物，其中該式 1 ii 的化合物與該式 1 i 的化合物的比率大於90 : 10。 Embodiment S4b. The composition as described in embodiment S4, wherein the ratio of the compound of formula 1 ii to the compound of formula 1 i is greater than 90:10.
實施方式S4c. 如實施方式S4所述之組成物，其中該式 1 ii 的化合物與該式 1 i 的化合物的比率大於99 : 1。 Embodiment S4c. The composition as described in embodiment S4, wherein the ratio of the compound of formula 1 ii to the compound of formula 1 i is greater than 99:1.
實施方式S5. 如實施方式1-37b中任一項所述之化合物，其中該式 1的化合物係式 1 iii 的化合物。 Embodiment S5. The compound according to any one of embodiments 1-37b, wherein the compound of formula 1 is the compound of formula 1 iii .
實施方式S6. 如實施方式1-37b中任一項所述之化合物，其中該式 1的化合物係式 1 iv 的化合物。 Embodiment S6. The compound according to any one of embodiments 1-37b, wherein the compound of formula 1 is the compound of formula 1 iv .
本揭露之實施方式（包括上述實施方式1-S6以及本文所述之任何其他實施方式）可以以任何方式組合，並且實施方式中變數的描述不僅關於式 1的化合物，而且還關於對於製備式 1的化合物有用的起始化合物和中間體化合物。另外，本揭露之實施方式（包括上述實施方式1-S6以及本文所述之任何其他實施方式）及其任何組合關於本揭露之組成物和方法。 Embodiments of the present disclosure (including Embodiments 1-S6 above and any other embodiments described herein) may be combined in any manner, and the description of variables in the embodiments is not only with respect to compounds of Formula 1 , but also for the preparation of Formula 1 The compounds are useful starting compounds and intermediate compounds. In addition, embodiments of the disclosure (including Embodiments 1-S6 above and any other embodiments described herein) and any combination thereof pertain to compositions and methods of the disclosure.
實施方式1-S6的組合如下所示：The combination of embodiment 1-S6 is as follows:
實施方式A. 一種式 1的化合物，其中 R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 1-C 4烷硫基、C 1-C 4鹵代烷硫基、C 1-C 4烷基亞磺醯基、C 1-C 4鹵代烷基亞磺醯基、C 1-C 4烷基磺醯基或C 1-C 4鹵代烷基磺醯基； R 5、R 6和R 7各自獨立地是氫、鹵素、氰基、C 1-C 4烷基、C 1-C 4鹵代烷基、C 1-C 4烷氧基、C 1-C 4鹵代烷氧基、C 1-C 4烷硫基、C 1-C 4鹵代烷硫基、C 1-C 4烷基亞磺醯基、C 1-C 4鹵代烷基亞磺醯基、C 1-C 4烷基磺醯基或C 1-C 4鹵代烷基磺醯基； W係O； Y係氫、C(=O)R 8、S(=O) nR 9、CO 2R 10、C(=O)NR 11R 12、S(=O) nNR 11R 12、NR 11R 12、C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基、C 1-C 6鹵代烷基、C 2-C 6鹵代烯基、C 2-C 6鹵代炔基、C 3-C 8環烷基、C 3-C 8鹵代環烷基、C 3-C 8環烯基、C 3-C 8鹵代環烯基、C 4-C 10烷基環烷基、C 4-C 10環烷基烷基、C 4-C 10鹵代環烷基烷基、C 6-C 14環烷基環烷基、C 5-C 10烷基環烷基烷基、C 2-C 8烷氧基烷基、C 2-C 8鹵代烷氧基烷基、C 4-C 10環烷氧基烷基、C 3-C 8烷氧基烷氧基烷基、C 2-C 6烷硫基烷基、C 2-C 6烷基亞磺醯基烷基、C 2-C 6烷基磺醯基烷基、C 2-C 6烷基胺基烷基、C 2-C 6鹵代烷基胺基烷基、C 3-C 8二烷基胺基烷基、C 4-C 10環烷基胺基烷基或C 3-C 5烷氧基羰基烷基；並且 J係苯基或萘基，每個環或環系統視需要被最多4個獨立地選自R JC的取代基取代；或5員或6員雜環或者8員、9員或10員二環系統，每個環或環系統含有選自碳原子和1至3個雜原子的環成員，該等雜原子獨立地選自最多1個硼、最多2個氧、最多1個硫和最多3個氮原子，其中最多1個碳環成員視需要選自C(=O)和C(=S)，每個環系統視需要被最多4個取代基取代，該等取代基獨立地選自碳原子環成員上的R JC、氮原子環成員上的R JN和硼原子環成員上的R JB。 Embodiment A. A compound of formula 1 , wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 1 -C 4 alkylsulfinyl, C 1 - C 4 Haloalkylsulfinyl, C 1 -C 4 Alkylsulfonyl or C 1 -C 4 Haloalkylsulfonyl; R 5 , R 6 and R 7 are each independently hydrogen, halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfinyl or C 1 -C 4 haloalkylsulfinyl; W series O; Y is hydrogen, C(=O)R 8 , S(=O) n R 9 , CO 2 R 10 , C(=O)NR 11 R 12 , S(=O) n NR 11 R 12 , NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 halocycloalkyl, C 3 -C 8 cycloalkenyl, C 3 -C 8 halocycloalkenyl, C 4 -C 10 alkylcycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 10 halocycloalkylalkyl, C 6 -C 14 cycloalkylcycloalkyl, C 5 -C 10 alkyl Cycloalkylalkyl, C 2 -C 8 alkoxyalkyl, C 2 -C 8 haloalkoxyalkyl, C 4 -C 10 cycloalkoxyalkyl, C 3 -C 8 alkoxyalkoxy C 2 -C 6 alkylthioalkyl, C 2 -C 6 alkylsulfinylalkyl, C 2 -C 6 alkylsulfonylalkyl, C 2 -C 6 alkylamine C 2 -C 6 haloalkylaminoalkyl, C 3 -C 8 dialkylaminoalkyl, C 4 -C 10 cycloalkylaminoalkyl or C 3 -C 5 alkoxy Carbonylalkyl; and J is phenyl or naphthyl, each ring or ring system is optionally substituted by up to 4 substituents independently selected from R JC ; or 5- or 6-membered heterocycle or 8- or 9-membered or 10-membered bicyclic ring systems, each ring or ring system containing ring members selected from carbon atoms and 1 to 3 heteroatoms independently selected from up to 1 boron, up to 2 oxygen, up to 1 Sulfur and up to 3 nitrogen atoms, with up to 1 carbon ring member optionally selected from C(=O) and C(=S), per ring system Optionally substituted with up to 4 substituents independently selected from R JC on carbon ring members, R JN on nitrogen ring members and R JB on boron ring members.
實施方式B. 如式 1或實施方式A所述之化合物，其中 J選自如示例1中所示的U-1至U-61，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2或3；或者 J選自如示例3中所示的U-81至U-124，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2或3。 Embodiment B. A compound as described in Formula 1 or Embodiment A, wherein J is selected from U-1 to U-61 as shown in Example 1, wherein at most 1 carbon ring member is optionally selected from C(=0) and when R v is attached to a carbon ring member, said R v is selected from R JC , and when R v is attached to a nitrogen ring member, said R v is selected from R JN ; and r is 0, 1, 2 or 3; or J is selected from U-81 to U-124 as shown in Example 3, wherein up to 1 carbon ring member is optionally selected from C(=0); and when R v is attached to the carbon ring member , said R v is selected from R JC , and when R v is attached to a nitrogen ring member, said R v is selected from R JN ; and r is 0, 1, 2 or 3.
實施方式C. 如實施方式B所述之化合物，其中 R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基； R 5、R 6和R 7各自獨立地是氫、鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基； Y係氫或C 1-C 6烷基； R 13係鹵素； 每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、硝基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2； 每個R JN獨立地是氫、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18或S(=O) nR 21； 每個R 17獨立地是氫、C(=O)R 23、C(=O)OR 24、C(=O)NR 25R 26或S(=O) nR 21；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被1至3個獨立地選自R x的取代基取代；並且 每個R 18獨立地是氫；或C 1-C 6烷基、C 3-C 7環烷基、C 2-C 7烷基羰基或C 2-C 7烷氧基羰基，每個視需要被1至3個獨立地選自R x的取代基取代；或者 R 17和R 18連同它們所附接的氮一起形成3員至5員環，該環含有選自碳原子和最多兩個獨立地選自氮、硫和氧的另外原子的環成員，其中硫原子環成員選自S、S(=O)和S(=O) 2，所述環視需要被1至3個獨立地選自以下各項的取代基取代：鹵素、C 1-C 2烷基、C 1-C 2鹵代烷基、C 1-C 2烷氧基、C 1-C 2鹵代烷氧基、氰基和硝基。 Embodiment C. The compound according to embodiment B, wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl; R 5 , R 6 and R 7 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl; Y is hydrogen or C 1 -C 6 alkyl; R 13 is halogen; each R JC are independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , C(= NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, nitro, OR 14 , C(=O)R 15 , C(= O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; each R JN is independently hydrogen, Hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S( =0) n R 21 or Q 2 ; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl, each optionally replaced by one or a plurality of substituents independently selected from the following: halogen, cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 or S(=O) n R 21 ; each R 17 is independently hydrogen, C(=O)R 23 , C(=O)OR 24 , C( =O) NR 25 R 26 or S(=O) n R 21 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally selected from 1 to 3 independently selected from R x and each R 18 is independently hydrogen; or C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 7 alkylcarbonyl or C 2 -C 7 alkoxy Carbonyl, each optionally substituted with 1 to 3 substituents independently selected from R ; or R and R together with the nitrogen to which they are attached form a 3- to 5-membered ring containing carbons selected from atom and up to two ring members of additional atoms independently selected from nitrogen, sulfur and oxygen, wherein the sulfur atom rings into Members are selected from S, S(=O) and S(=O) 2 , and the ring needs to be substituted by 1 to 3 substituents independently selected from the following: halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, cyano and nitro.
實施方式D. 如實施方式C所述之化合物，其中 R 1、R 2、R 3和R 4各自係氫； R 5、R 6和R 7各自係氫； J選自U-1至U-61、U-90至U-96、U-105、U-110或U-117至U-124，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2或3； 每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基、C 2-C 6烯基、C 2-C 6炔基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、C(=NR 19)R 20、NR 17R 18或S(=O) nR 21； 每個R JN獨立地是氫、羥基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18或S(=O) nR 21； 每個R 17獨立地是氫、C(=O)R 23、C(=O)OR 24或C(=O)NR 25R 26；或C 1-C 4烷基，其視需要被1至3個獨立地選自R x的取代基取代；並且 每個R 18獨立地是氫、C 1-C 4烷基、C 3-C 5環烷基、C 2-C 5烷基羰基或C 2-C 5烷氧基羰基。 Embodiment D. The compound as described in Embodiment C, wherein R 1 , R 2 , R 3 and R 4 are each hydrogen; R 5 , R 6 and R 7 are each hydrogen; J is selected from U-1 to U- 61. U-90 to U-96, U-105, U-110 or U-117 to U-124, wherein up to 1 carbon ring member is optionally selected from C (=O); and when R v is attached to When R v is a carbon ring member, said R v is selected from R JC , and when R v is attached to a nitrogen ring member, said R v is selected from R JN ; and r is 0, 1, 2 or 3; each R JC are independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl , each optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(= Z) NR 17 R 18 , C(=NR 19 )R 20 , NR 17 R 18 or S(=O) n R 21 ; each R JN is independently hydrogen, hydroxyl, OR 14 , C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl groups, each optionally substituted with one or more substituents independently selected from the group consisting of halogen, cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 , C(=Z)NR 17 R 18 or S(=O) n R 21 ; each R 17 is independently hydrogen, C(=O)R 23 , C(=O)OR 24 or C(=O) NR 25 R 26 ; or C 1 -C 4 alkyl optionally substituted by 1 to 3 substituents independently selected from R x ; and each R 18 is independently hydrogen, C 1 -C 4 alkyl , C 3 -C 5 cycloalkyl, C 2 -C 5 alkylcarbonyl or C 2 -C 5 alkoxycarbonyl.
實施方式E. 如實施方式D所述之化合物，其中 Y係氫或甲基； J選自U-1、U-2、U-4、U-26、U-28、U-37、U-38、U-39、U-49、U-50、U-51、U-53、U-56、U-91、U-94、U-95、U-96、U-110、U-117、U-118或U-124，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2或3； 每個R 17獨立地是氫、C(=O)R 23、C(=O)OR 24或C(=O)NR 25R 26；或C 1-C 4烷基或C 3-C 5環烷基，每個視需要被1至3個獨立地選自R x的取代基取代；並且 每個R 18獨立地是氫或C 1-C 4烷基。 Embodiment E. The compound as described in embodiment D, wherein Y is hydrogen or methyl; J is selected from U-1, U-2, U-4, U-26, U-28, U-37, U- 38, U-39, U-49, U-50, U-51, U-53, U-56, U-91, U-94, U-95, U-96, U-110, U-117, U-118 or U-124, wherein up to 1 carbon ring member is optionally selected from C(=O); and when R v is attached to a carbon ring member, said R v is selected from R JC , and when R v When attached to a nitrogen ring member, said R v is selected from R JN ; and r is 0, 1, 2 or 3; each R 17 is independently hydrogen, C(=O)R 23 , C(=O) OR 24 or C(=O)NR 25 R 26 ; or C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl, each optionally substituted by 1 to 3 substituents independently selected from R x and each R 18 is independently hydrogen or C 1 -C 4 alkyl.
實施方式F. 如式 1或實施方式E所述之化合物，其中 Y係氫； J選自U-1、U-2、U-4、U-26、U-37、U-38、U-39、U-49、U-50、U-51或U-91，其中最多1個碳環成員視需要選自C(=O)；並且當R v附接到碳環成員時，所述R v選自R JC，並且當R v附接到氮環成員時，所述R v選自R JN；並且r係0、1、2或3； 每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、CO 2H、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18或S(=O) nR 21； 每個R JN獨立地是氫、羥基、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、CO 2H、C(=O)OR 16或C(=Z)NR 17R 18； 每個R 17獨立地是氫；或C 1-C 4烷基或C 3-C 5環烷基，每個視需要被1至3個獨立地選自R x的取代基取代；以及 每個R 18係氫。 Embodiment F. The compound as described in formula 1 or embodiment E, wherein Y is hydrogen; J is selected from U-1, U-2, U-4, U-26, U-37, U-38, U- 39. U-49, U-50, U-51 or U-91, wherein up to 1 carbon ring member is optionally selected from C(=O); and when R v is attached to a carbon ring member, said R v is selected from R JC , and when R v is attached to a nitrogen ring member, said R v is selected from R JN ; and r is 0, 1, 2 or 3; each R JC is independently hydrogen, halogen, hydroxyl , cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 , S(=O) n R 21 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, CO 2 H, C( =O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 or S(=O) n R 21 ; each R JN is independently hydrogen, hydroxyl, C(=O)R 15 , C (=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally replaced by one or Substituted by a plurality of substituents independently selected from the group consisting of halogen, cyano, C(=O)R 15 , CO 2 H, C(=O)OR 16 or C(=Z)NR 17 R 18 ; each Each R is independently hydrogen; or C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl, each optionally substituted by 1 to 3 substituents independently selected from R x ; and each R 18 is hydrogen.
實施方式G. 如實施方式F所述之化合物，其中 J選自U-1或U-26；或U-50，其中最多1個碳環成員視需要選自C(=O)； 每個R JC獨立地是氫、鹵素、羥基、氰基、OR 14、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18、NR 17R 18、S(=O) nR 21或Q 2；或C 1-C 6烷基或C 3-C 6環烷基，每個視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)OR 16或C(=Z)NR 17R 18； 每個R JN獨立地是氫、C(=O)R 15、C(=O)OR 16、C(=Z)NR 17R 18或NR 17R 18；或C 1-C 6烷基，其視需要被一個或多個獨立地選自以下各項的取代基取代：鹵素、氰基、C(=O)R 15、C(=O)OR 16或C(=Z)NR 17R 18；以及 R 17獨立地是C 1-C 4烷基或C 3-C 5環烷基，每個視需要被1至3個獨立地選自R x的取代基取代。 Embodiment G. The compound of embodiment F, wherein J is selected from U-1 or U-26; or U-50, wherein up to 1 carbon ring member is optionally selected from C(=O); each R JC is independently hydrogen, halogen, hydroxyl, cyano, OR 14 , C(=O)R 15 , C(=O)OR 16 , C(=Z)NR 17 R 18 , NR 17 R 18 , S(= O) n R 21 or Q 2 ; or C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, each optionally substituted by one or more substituents independently selected from the following: halogen, cyano, C(=O)OR 16 or C(=Z)NR 17 R 18 ; each R JN is independently hydrogen, C(=O)R 15 , C(=O)OR 16 , C(=Z ) NR 17 R 18 or NR 17 R 18 ; or C 1 -C 6 alkyl optionally substituted by one or more substituents independently selected from the group consisting of halogen, cyano, C(=O) R 15 , C(=O)OR 16 or C(=Z)NR 17 R 18 ; and R 17 is independently C 1 -C 4 alkyl or C 3 -C 5 cycloalkyl, each optionally replaced by 1 to 3 substituents independently selected from Rx .
實施方式H. 一種殺昆蟲組成物，該殺昆蟲組成物包含：
至少一種選自式
8a的化合物、其
N-氧化物和鹽的化合物：
實施方式I. 如實施方式H所述之殺昆蟲組成物，其中 R 1、R 2、R 3和R 4各自獨立地是氫、鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基； R 5、R 6和R 7各自獨立地是氫、鹵素、C 1-C 4烷基或C 1-C 4鹵代烷基；以及 W係O。 Embodiment I. The insecticidal composition according to embodiment H, wherein R 1 , R 2 , R 3 and R 4 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkane R 5 , R 6 and R 7 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl; and W is O.
實施方式J. 如實施方式I所述之殺昆蟲組成物，其中 R 1、R 2、R 3、R 4、R 5、R 6和R 7各自係氫。 Embodiment J. The insecticidal composition of embodiment I, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each hydrogen.
實施方式K. 如實施方式H所述之殺昆蟲組成物，其中該式 8a的化合物係(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲醯胺。 Embodiment K. The insecticidal composition according to embodiment H, wherein the compound of formula 8a is (1 R ,5 R ,6 R )-2-oxabicyclo[3.1.0]hexane-6- Formamide.
實施方式L. 如實施方式H所述之殺昆蟲組成物，其中該式 8a的化合物係(1 S,5 S,6 S)-2-氧雜二環[3.1.0]己烷-6-甲醯胺。 Embodiment L. The insecticidal composition as described in embodiment H, wherein the compound of formula 8a is (1 S ,5 S ,6 S )-2-oxabicyclo[3.1.0]hexane-6- Formamide.
具體實施方式包括選自以下群組的式
1的化合物，該群組由以下各項組成：
值得注意的是，本揭露之化合物的特徵在於有利的代謝模式和/或土壤殘留模式，並且表現出防治廣譜農學和非農學無脊椎害蟲的活性。Notably, the compounds of the present disclosure are characterized by favorable metabolic and/or soil residue profiles and exhibit activity against a broad spectrum of agronomic and non-agronomic invertebrate pests.
特別值得注意的是，由於無脊椎害蟲防治譜和經濟學重要性的原因，藉由防治無脊椎害蟲來保護農業作物免受無脊椎害蟲引起的損害或傷害係本揭露之實施方式。本揭露之化合物由於其在植株中的有利轉移特性或內吸性（systemicity）還保護葉或不與式 1的化合物或包含該化合物的組成物直接接觸的其他植株部分。 Of particular note, because of the spectrum and economic importance of invertebrate pest control, the protection of agricultural crops from damage or injury caused by invertebrate pests by controlling invertebrate pests is an embodiment of the present disclosure. The compounds of the present disclosure also protect leaves or other plant parts that are not in direct contact with the compound of formula 1 or a composition comprising the compound due to its favorable transfer properties or systemicity in the plant.
還值得注意的作為本揭露之實施方式的是包含如前述實施方式中任一項以及本文所述之任何其他實施方式及其任何組合所述之化合物，以及至少一種選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的附加組分的組成物，所述組成物視需要進一步包含至少一種附加生物學活性化合物或藥劑。Also noteworthy as an embodiment of the present disclosure is the inclusion of a compound as described in any one of the preceding embodiments and any other embodiment described herein and any combination thereof, and at least one selected from the group consisting of surfactants, solid diluents Compositions of additional components of the group consisting of agents and liquid diluents, said compositions optionally further comprising at least one additional biologically active compound or agent.
另外值得注意的作為本揭露之實施方式的是用於防治無脊椎害蟲的包含如前述實施方式中任一項以及本文所述之任何其他實施方式及其任何組合所述之化合物，以及至少一種選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的附加組分的組成物，所述組成物視需要進一步包含至少一種附加生物學活性化合物或藥劑。本揭露之實施方式進一步包括用於防治無脊椎害蟲之方法，該等方法包括使無脊椎害蟲或其環境與生物學有效量的如前述實施方式中任一項所述之化合物（例如，作為本文所述之組成物）接觸。Also noteworthy as an embodiment of the present disclosure is a compound for controlling invertebrate pests comprising any one of the preceding embodiments and any other embodiment described herein and any combination thereof, and at least one optional Compositions of additional components from the group consisting of surfactants, solid diluents and liquid diluents, said compositions optionally further comprising at least one additional biologically active compound or agent. Embodiments of the present disclosure further include methods for controlling invertebrate pests, the methods comprising administering to the invertebrate pest or its environmentally and biologically effective amount of a compound as described in any one of the preceding embodiments (for example, as described herein said composition) contact.
本揭露之實施方式還包括呈土壤浸液液體製劑形式的包含如前述實施方式中任一項所述之化合物的組成物。本揭露之實施方式進一步包括用於防治無脊椎害蟲之方法，該等方法包括使土壤與作為土壤浸液的液體組成物接觸，該土壤浸液包含生物學有效量的如前述實施方式中任一項所述之化合物。Embodiments of the present disclosure also include compositions comprising a compound as described in any one of the preceding embodiments in the form of a soil drench liquid formulation. Embodiments of the present disclosure further include methods for controlling invertebrate pests comprising contacting soil with a liquid composition as a soil soak comprising a biologically effective amount of Compounds mentioned in this item.
本揭露之實施方式還包括用於防治無脊椎害蟲的噴霧組成物，該噴霧組成物包含生物學有效量的如前述實施方式中任一項所述之化合物以及推進劑。本揭露之實施方式進一步包括用於防治無脊椎害蟲的誘餌組成物，該誘餌組成物包含生物學有效量的如前述實施方式中任一項所述之化合物、一種或多種食物材料、視需要的引誘劑和視需要的濕潤劑。本揭露之實施方式還包括一種用於防治無脊椎害蟲的裝置，該裝置包含所述誘餌組成物和被適配成用於容納所述誘餌組成物的外殼，其中外殼具有至少一個開口，該開口的大小被設定成允許無脊椎害蟲通過開口，使無脊椎害蟲能夠從外殼外部的位置接近所述誘餌組成物，並且其中外殼進一步被適配成放置在無脊椎害蟲可能或已知的活動所在地中或附近。Embodiments of the present disclosure also include a spray composition for controlling invertebrate pests, the spray composition comprising a biologically effective amount of a compound as described in any one of the preceding embodiments and a propellant. Embodiments of the present disclosure further include a bait composition for controlling invertebrate pests, the bait composition comprising a biologically effective amount of a compound as described in any one of the preceding embodiments, one or more food materials, optionally Attractant and if needed wetting agent. Embodiments of the present disclosure also include a device for controlling invertebrate pests, the device comprising the bait composition and a housing adapted to accommodate the bait composition, wherein the housing has at least one opening, the opening is sized to allow passage of an invertebrate pest through an opening enabling the invertebrate pest to access the bait composition from a location external to the enclosure, and wherein the enclosure is further adapted to be placed in a locus where the invertebrate pest is likely or known to be active or nearby.
本揭露之實施方式還包括用於保護種子免受無脊椎害蟲侵害之方法，該等方法包括使種子與生物學有效量的如前述實施方式中任一項所述之化合物接觸。Embodiments of the present disclosure also include methods for protecting seed from invertebrate pests comprising contacting the seed with a biologically effective amount of a compound as described in any one of the preceding embodiments.
本揭露之實施方式還包括用於保護動物免受無脊椎寄生性害蟲侵害之方法，該等方法包括向動物施用殺寄生蟲有效量的如前述實施方式中任一項所述之化合物。Embodiments of the present disclosure also include methods for protecting an animal from an invertebrate parasitic pest comprising administering to the animal a parasiticidally effective amount of a compound as described in any one of the preceding embodiments.
本揭露之實施方式還包括用於防治無脊椎害蟲之方法，該等方法包括使無脊椎害蟲或其環境與生物學有效量的式 1的化合物、其 N-氧化物或鹽（例如，作為本文所述之組成物）接觸，前提係該等方法不是藉由治療對人體或動物體進行醫學治療之方法。 Embodiments of the present disclosure also include methods for controlling invertebrate pests, the methods comprising administering to the invertebrate pest or its environmentally and biologically effective amount of a compound of formula 1 , its N -oxide or salt (for example, as described herein composition) provided that such methods are not methods of medical treatment of the human or animal body by therapy.
本揭露還關於這樣之方法，其中無脊椎害蟲或其環境與包含生物學有效量的式 1的化合物、其 N-氧化物或鹽以及至少一種選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的附加組分的組成物接觸，所述組成物視需要進一步包含生物學有效量的至少一種附加生物學活性化合物或藥劑，前提係該等方法不是藉由治療對人體或動物體進行醫學治療之方法。 The present disclosure also relates to a method wherein the invertebrate pest or its environment is mixed with a biologically effective amount of a compound of formula 1 , its N -oxide or salt and at least one selected from the group consisting of surfactants, solid diluents and liquid diluents. contact with a composition of additional components of the group of constituents, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent, provided that the methods are not by treatment of the human or animal body Methods of medical treatment.
本揭露之實施方式還包括使用無人駕駛飛機（UAV）將本文揭露的組成物分散在種植區域上。在一些實施方式中，種植區域係含有作物的區域。在一些實施方式中，作物選自單子葉植物或雙子葉植物。在一些實施方式中，作物選自稻、玉米、大麥、大豆、小麥、蔬菜、煙草、茶樹、果樹和甘蔗。在一些實施方式中，本文揭露的組成物被配製用於以超低體積噴霧。由無人機施加的產品可以使用水或油作為噴霧載體。全球用於無人機施加的典型噴霧體積（包括產品）為5.0升/公頃-100升/公頃（約0.5-10 gpa）。這包括超低噴霧體積（ULV）至低噴霧體積（LV）的範圍。儘管不常見，但可能存在可以使用甚至更低的噴霧體積（低至1.0升/公頃（0.1 gpa））的情況。Embodiments of the present disclosure also include the use of unmanned aerial vehicles (UAVs) to disperse the compositions disclosed herein over the planting area. In some embodiments, a growing area is an area containing a crop. In some embodiments, the crop plants are selected from monocots or dicots. In some embodiments, the crop is selected from rice, corn, barley, soybean, wheat, vegetable, tobacco, tea tree, fruit tree, and sugar cane. In some embodiments, the compositions disclosed herein are formulated for nebulization at ultra-low volumes. Products applied by drone can use water or oil as a spray carrier. Typical spray volumes (including product) for drone application worldwide are 5.0 L/ha-100 L/ha (approximately 0.5-10 gPa). This includes the Ultra Low Spray Volume (ULV) to Low Spray Volume (LV) range. Although uncommon, there may be instances where even lower spray volumes (as low as 1.0 L/ha (0.1 gpa)) can be used.
式 1的化合物可以藉由如下列方案1-10中描述的一種或多種方法和變體來製備。除非另有說明，否則下文式 1- 11的化合物中的取代基的定義如上文發明內容中所定義。式 1a的化合物係式 1的化合物的子集。式 8a係式 8的子集；除非另有說明，否則每個子集式的取代基如其母體式所定義。環境溫度或室溫定義為約20°C-25°C。 Compounds of Formula 1 can be prepared by one or more of the methods and variants as described in Schemes 1-10 below. Unless otherwise stated, the definitions of the substituents in the compounds of Formulas 1-11 below are as defined above in the Summary of the Invention. Compounds of Formula 1a are a subset of compounds of Formula 1 . Formula 8a is a subset of Formula 8 ; unless otherwise stated, the substituents of each subset are as defined for its parent formula. Ambient or room temperature is defined as about 20°C-25°C.
如方案1中所示，式 1的化合物可藉由使式 2的酸與式 3的胺在偶合試劑存在下反應來製備。有用的偶合試劑包括例如二環己基碳二亞胺、1-(3-二甲基胺基丙基)-3-乙基碳二亞胺（EDC）和羰基二咪唑。可用於該方法的另外的偶合試劑包括 O-(7-氮雜苯并三唑-1-基)- N,N,N',N'-四甲基脲鎓六氟磷酸鹽（HATU）、丙基膦酸酐（T3P）、 O-(7-氮雜苯并三唑-1-基)- N,N,N',N'-四甲基脲鎓四氟硼酸鹽（TATU）和2-(1 H-苯并三唑-1-基)-1,1,3,3-四甲基脲鎓六氟磷酸鹽（HBTU）。該等偶合試劑通常在鹼諸如三乙胺、吡啶、4-(二甲基胺基)吡啶或 N, N-二異丙基乙胺存在下使用。典型的反應條件包括無水非質子溶劑諸如乙酸乙酯、二氯甲烷、四氫呋喃或 N, N-二甲基甲醯胺，以及室溫與80°C之間的反應溫度。對於可用於方案1之方法中的反應條件以及其他充分確立的偶合條件，參見例如 Bioorganic & Medicinal Chemistry[生物有機與藥物化學], 2015, 23(3), 564； Journal of Organic Chemistry[有機化學雜誌] 2008, 73(7), 2731-2737； Tetrahedron Letters[四面體通訊] 2009, 50(45), 6200-6202；以及 Organic letters[有機通訊] 2011, 13(12), 2988-91。本實例1的步驟C也說明了方案1之方法。式 3的胺係可商購的或可以藉由本領域充分確立之方法製備。 As shown in Scheme 1, compounds of Formula 1 can be prepared by reacting an acid of Formula 2 with an amine of Formula 3 in the presence of a coupling reagent. Useful coupling reagents include, for example, dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), and carbonyldiimidazole. Additional coupling reagents that can be used in this method include O- (7-azabenzotriazol-1-yl)-N ,N,N',N' -tetramethyluronium hexafluorophosphate (HATU), Propylphosphonic anhydride (T3P), O -(7-azabenzotriazol-1-yl) -N,N,N',N' -tetramethyluronium tetrafluoroborate (TATU) and 2- ( 1H -Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). These coupling reagents are usually used in the presence of a base such as triethylamine, pyridine, 4-(dimethylamino)pyridine or N , N -diisopropylethylamine. Typical reaction conditions include anhydrous aprotic solvents such as ethyl acetate, dichloromethane, tetrahydrofuran or N , N -dimethylformamide, and reaction temperatures between room temperature and 80°C. For reaction conditions that can be used in the method of Scheme 1, as well as other well-established coupling conditions, see, for example, Bioorganic & Medicinal Chemistry [bioorganic and medicinal chemistry], 2015 , 23 (3), 564; Journal of Organic Chemistry [Organic Chemistry Journal ] 2008 , 73 (7), 2731-2737; Tetrahedron Letters [Tetrahedron Letters] 2009 , 50 (45), 6200-6202; and Organic letters [Organic Letters] 2011 , 13 (12), 2988-91. Step C of this Example 1 also illustrates the method of Scheme 1. Amines of formula 3 are either commercially available or can be prepared by methods well established in the art.
方案1
替代性地，如方案2中所示，式 1的化合物可藉由使式 4的醯氯與式 3的胺在酸清除劑存在下反應來製備。典型的酸清除劑包括胺鹼諸如三乙胺、 N, N-二異丙基乙胺和吡啶。其他清除劑包括氫氧化物諸如氫氧化鈉和氫氧化鉀，或碳酸鹽諸如碳酸鈉和碳酸鉀。典型的反應條件包括有機溶劑諸如乙酸乙酯、二氯甲烷、四氫呋喃或 N, N-二甲基甲醯胺，以及室溫與80°C之間的反應溫度。在某些情況下，使用聚合物負載的酸清除劑諸如聚合物結合的 N, N-二異丙基乙胺和聚合物結合的4-(二甲基胺基)吡啶係有用的。 Alternatively, as shown in Scheme 2, compounds of Formula 1 can be prepared by reacting an acid chloride of Formula 4 with an amine of Formula 3 in the presence of an acid scavenger. Typical acid scavengers include amine bases such as triethylamine, N , N -diisopropylethylamine and pyridine. Other scavengers include hydroxides such as sodium hydroxide and potassium hydroxide, or carbonates such as sodium carbonate and potassium carbonate. Typical reaction conditions include organic solvents such as ethyl acetate, dichloromethane, tetrahydrofuran or N , N -dimethylformamide, and reaction temperatures between room temperature and 80°C. In some cases, the use of polymer-supported acid scavengers such as polymer-bound N , N -diisopropylethylamine and polymer-bound 4-(dimethylamino)pyridine is useful.
方案2
鏡像異構物富集的式 1 i 和 1 ii 的化合物可以藉由利用熟知的手性層析分離方法由式 1 i 和 1 ii 的化合物的外消旋混合物獲得。鏡像異構物富集的式 1 iii 和 1 iv 的化合物還可以使用該等熟知的手性層析分離方法由式 1 iii 和 1 iv 的化合物的外消旋混合物獲得。關於手性分離方法的廣泛綜述，參見 Chiral Separations : Methods and Protocols[手性分離：方法和方案] (Methods in Molecular Biology [分子生物學方法]), 第2版, 2013版, Gerhard K. E. Scriba (編者)。本實例1的步驟D也說明了手性分離方法。 Enantiomerically enriched compounds of formula 1 i and 1 ii can be obtained from racemic mixtures of compounds of formula 1 i and 1 ii by employing well-known chiral chromatographic separation methods. Enantiomerically enriched compounds of formulas 1 iii and 1 iv can also be obtained from racemic mixtures of compounds of formulas 1 iii and 1 iv using such well known chiral chromatographic separation methods. For an extensive review of chiral separation methods, see Chiral Separations : Methods and Protocols (Methods in Molecular Biology), 2nd edition, 2013 edition, Gerhard KE Scriba (ed. ). Step D of this Example 1 also illustrates a chiral separation method.
如方案3所示，式 4的醯氯（其中W係O）容易由式 2的羧酸藉由多種熟知之方法製備。例如，使羧酸與氯化試劑諸如亞硫醯氯、草醯氯或三氯氧磷在溶劑諸如二氯甲烷或甲苯中並視需要在催化量的 N, N-二甲基甲醯胺存在下反應可提供相應的式 4的醯氯。 As shown in Scheme 3, acyl chlorides of formula 4 (where W is O) are readily prepared from carboxylic acids of formula 2 by a variety of well-known methods. For example, combining a carboxylic acid with a chlorinating agent such as thionyl chloride, oxalyl chloride, or phosphorus oxychloride in a solvent such as dichloromethane or toluene and optionally in the presence of a catalytic amount of N , N -dimethylformamide The following reaction can provide the corresponding acyl chloride of formula 4 .
方案3
如方案4中所示，式 2的羧酸（其中W係O）可根據熟知的式 5的相應化合物的鹼性或酸性水解方法製備，較佳的是使用略微過量的氫氧化物鹼（例如氫氧化鋰、氫氧化鈉或氫氧化鉀）在含水或不含水的水混溶性溶劑諸如甲醇、乙醇、四氫呋喃或1,4-二㗁𠮿中，在0°C與80°C之間的溫度下。可以藉由將pH調節至約1至3，並然後過濾或萃取（視需要在藉由蒸發除去有機溶劑後），分離產物（參見例如US 2015/0023913）。本實例1的步驟B也說明了方案4之方法。 As shown in Scheme 4, carboxylic acids of formula 2 (where W is O) can be prepared according to the well-known basic or acidic hydrolysis of the corresponding compound of formula 5 , preferably using a slight excess of hydroxide base (e.g. Lithium hydroxide, sodium hydroxide or potassium hydroxide) in aqueous or non-aqueous water-miscible solvents such as methanol, ethanol, tetrahydrofuran or 1,4-di㗁𠮿 at temperatures between 0°C and 80°C Down. The product can be isolated by adjusting the pH to about 1 to 3, and then filtering or extracting, optionally after removal of the organic solvent by evaporation (see eg US 2015/0023913). Step B of this Example 1 also illustrates the method of Scheme 4.
方案4
如方案5中所示，式 5的化合物可藉由在過渡金屬催化劑諸如Rh 2OAc 4（即乙酸銠(II)二聚體）、Rh 2oct 4（即辛酸銠(II)二聚體）、Rh 2esp 2（即雙[銠(α,α,α′,α′-四甲基-1,3-苯二丙酸)]）或硫酸銅(II)存在下用式7的重氮酯使式 6的烯烴環丙烷化來製備。該反應可以在除了式 6和 7的化合物之外沒有溶劑的情況下進行。更典型地，反應在液相中用溶劑諸如二氯甲烷、己烷或甲苯進行，並且反應溫度介於-78與110°C之間。重氮酯與烯烴的環丙烷化的一般程序在化學文獻中有詳細記載，參見例如WO 1998/057968。本實例1的步驟A也說明了方案5之方法。式 7的化合物係可商購的或可藉由本領域熟知之方法製備。 As shown in Scheme 5, the compound of formula 5 can be obtained by reaction with a transition metal catalyst such as Rh 2 OAc 4 (i.e. rhodium acetate (II) dimer), Rh 2 oct 4 (i.e. rhodium octanoate (II) dimer) , Rh 2 esp 2 (that is, bis[rhodium (α, α, α', α'-tetramethyl-1,3-benzenedipropionic acid)]) or copper sulfate (II) in the presence of the diazo of formula 7 Esters are prepared by cyclopropanation of alkenes of formula 6 . This reaction can be carried out without a solvent other than the compounds of formulas 6 and 7 . More typically, the reaction is performed in the liquid phase with a solvent such as dichloromethane, hexane or toluene, and the reaction temperature is between -78 and 110°C. The general procedure for the cyclopropanation of diazoesters with alkenes is well documented in the chemical literature, see eg WO 1998/057968. Step A of this Example 1 also illustrates the method of Scheme 5. Compounds of formula 7 are commercially available or can be prepared by methods well known in the art.
方案5
如方案6中所示，式 1的化合物還可以藉由式 8的化合物與式 9的化合物的過渡金屬催化的交叉偶合來製備，其中Lg係脫離基諸如鹵化物基團（例如Cl、Br、I）或磺酸酯基團（例如甲磺酸酯、三氟甲磺酸酯、對甲苯磺酸酯的基團）等。這種類型的反應典型地使用鈀催化劑諸如乙酸鈀(II)與膦配位基諸如 t-BuBrettPhos（即2-(二三級丁基膦基)-2′,4′,6′-三異丙基-3,6-二甲氧基-1,1′-聯苯），或銅催化劑諸如碘化亞銅(I)與二胺配位基諸如 反式- N, N′-二甲基環己烷-1,2-二胺進行。該等反應傳統上需要在有機溶劑諸如三級丁醇、甲苯或二㗁𠮿中在存在鹼諸如碳酸鉀或磷酸鉀並且反應溫度介於80與110°C之間（參見例如 Tetrahedron[四面體], 2009, 65, 6576）。式 9的化合物係可商購的或可藉由本領域充分確立之方法製備。 As shown in Scheme 6, compounds of formula 1 can also be prepared by transition metal-catalyzed cross-coupling of compounds of formula 8 with compounds of formula 9 , wherein Lg is a leaving group such as a halide group (e.g., Cl, Br, I) or sulfonate groups (such as mesylate, triflate, p-toluenesulfonate groups), etc. This type of reaction typically uses a palladium catalyst such as palladium(II) acetate with a phosphine ligand such as t- BuBrettPhos (i.e. 2-(ditertiarybutylphosphino)-2',4',6'-triiso Propyl-3,6-dimethoxy-1,1′-biphenyl), or a copper catalyst such as copper(I) iodide with a diamine ligand such as trans - N , N ′-dimethyl Cyclohexane-1,2-diamine. These reactions traditionally require the presence of a base such as potassium carbonate or potassium phosphate in an organic solvent such as tert-butanol, toluene or dioxin at a reaction temperature between 80 and 110°C (see e.g. Tetrahedron [tetrahedron] , 2009 , 65 , 6576). Compounds of formula 9 are either commercially available or can be prepared by methods well established in the art.
方案6
在替代性方法中，如方案 7中所示，式 1的化合物可由式 8的醯胺藉由在鹼諸如氫化鈉存在下或在稀酸諸如鹽酸存在下與式 9的化合物（其中Lg係脫離基諸如鹵化物基團（例如Cl、Br、I））反應來製備。這種類型的反應典型地在溶劑諸如二甲亞碸、 N, N-二甲基甲醯胺或三級丁醇中，在從約室溫至反應混合物回流溫度範圍內的溫度下進行（參見例如US 2003119829 A1）。 In an alternative approach, as shown in Scheme 7 , a compound of formula 1 can be synthesized from an amide of formula 8 by cleavage with a compound of formula 9 (wherein Lg is Groups such as halide groups (e.g. Cl, Br, I)) are prepared. Reactions of this type are typically carried out in solvents such as dimethyloxide, N , N -dimethylformamide, or tert-butanol at temperatures ranging from about room temperature to the reflux temperature of the reaction mixture (see For example US 2003119829 A1).
方案7
如方案8中所示，在方案1和2的反應中，氨可替代式 3的化合物以產生式 8a（即，其中Y係H的式 8）的醯胺。式 4的醯氯也可以由式 2的化合物與亞硫醯氯在添加氨之前視需要在鹼諸如三乙胺或 N, N-二異丙基乙胺存在下原位產生。對於在方案8之方法中有用的反應條件，參見例 J. Am. Chem. Soc. [美國化學會誌] 2015, 137, 2042。 As shown in Scheme 8, ammonia can replace compounds of formula 3 in the reactions of schemes 1 and 2 to produce amides of formula 8a (ie, formula 8 where Y is H). Acyl chlorides of formula 4 can also be generated in situ from compounds of formula 2 with thionyl chlorides optionally in the presence of a base such as triethylamine or N , N -diisopropylethylamine prior to the addition of ammonia. For reaction conditions useful in the method of Scheme 8, see for example J. Am. Chem. Soc . [American Chemical Society] 2015 , 137 , 2042.
方案8
式 1a（即其中W係O的式 1）的化合物可藉由式 10的醇與式 3的胺的銠催化的氧化醯胺化來製備，如方案9中所示。此反應典型地在催化劑諸如Rh(COD) 2BF 4（即，雙(1,5-環辛二烯)四氟硼酸銠(I)）、配位基諸如4,5-雙(二苯基膦基)-9,9-二甲基𠮿口星（即，Xantphos）或1,4-雙(二苯基膦基)丁烷（即，DPPB）、氫受體諸如三氟苯乙酮和鹼諸如乙酸銫或碳酸銫的存在下進行。該反應可以在非質子溶劑諸如四氫呋喃或二㗁𠮿中進行，溫度在0-100°C的範圍內（參見例如 ACS Catalysis[ ACS催化], 2016, 6, 8214）。替代性地，式 1a的化合物可藉由使式 10的醇與式 3的胺在催化劑諸如釕RuHClCO(AsPh 3) 3（即，三(三苯基胂)羰基氫氯化釕(II)）存在下用合適的硫代甲醯胺配位基諸如2-吡啶硫代甲醯胺偶合來製備。該反應典型地在有氧條件下，在有機溶劑諸如乙醇中，在從約室溫至溶劑回流溫度範圍內的溫度下進行（參見例如 Organometallics[有機金屬], 2014, 33, 4269）。 Compounds of Formula 1a (ie, Formula 1 where W is O) can be prepared by rhodium-catalyzed oxidative amidation of alcohols of Formula 10 with amines of Formula 3 , as shown in Scheme 9. This reaction is typically performed over a catalyst such as Rh(COD) 2 BF 4 (i.e., rhodium(I) bis(1,5-cyclooctadiene)tetrafluoroborate), a ligand such as 4,5-bis(diphenyl Phosphino)-9,9-dimethyl (i.e., Xantphos) or 1,4-bis(diphenylphosphino)butane (i.e., DPPB), hydrogen acceptors such as trifluoroacetophenone and in the presence of a base such as cesium acetate or cesium carbonate. The reaction can be carried out in an aprotic solvent such as tetrahydrofuran or di㗁𠮿 at a temperature in the range of 0–100 °C (see for example ACS Catalysis [ ACS Catalysis], 2016 , 6 , 8214). Alternatively, compounds of formula 1a can be obtained by reacting an alcohol of formula 10 with an amine of formula 3 in a catalyst such as ruthenium RuHClCO(AsPh 3 ) 3 (i.e., tris(triphenylarsine)carbonyl ruthenium(II)hydrochloride) Prepared by coupling in the presence of a suitable thioformamide ligand such as 2-pyridinethioformamide. The reaction is typically performed under aerobic conditions in an organic solvent such as ethanol at a temperature ranging from about room temperature to the reflux temperature of the solvent (see eg Organometallics [Organometallics], 2014 , 33 , 4269).
如方案9中所示，式 1a（即其中W係O的式 1）的化合物也可藉由式 11的醛與式 3的胺的銠催化的氧化醯胺化來製備。 As shown in Scheme 9, compounds of Formula 1a (ie, Formula 1 where W is O) can also be prepared by rhodium-catalyzed oxidative amidation of aldehydes of Formula 11 with amines of Formula 3 .
方案9
如方案 10中所示，式 10的醇和式 11的醛可根據熟悉該項技術者已知的一般方法由式 5的酯製備。在一個實例中，適量的還原劑諸如二異丁基氫化鋁在非質子溶劑諸如二氯甲烷或四氫呋喃中在適當的溫度下導致式 5的化合物轉化成式 10和 11的化合物。 As shown in Scheme 10 , alcohols of formula 10 and aldehydes of formula 11 can be prepared from esters of formula 5 according to general methods known to those skilled in the art. In one example, an appropriate amount of a reducing agent such as diisobutylaluminum hydride in an aprotic solvent such as dichloromethane or tetrahydrofuran at an appropriate temperature results in the conversion of compounds of formula 5 to compounds of formula 10 and 11 .
方案10
藉由上述方法製備的其中W係O的式 1的化合物可使用多種標準硫化試劑諸如五硫化二磷或2,4-雙(4-甲氧基苯基)-1,3-二硫雜-2,4-二磷雜環丁烷-2,4-二硫化物（勞森試劑（Lawesson’s reagent））轉化為其中W係S的相應硫代醯胺。這種類型的反應係熟知的，參見例如 Heterocycles[雜環化合物] 1995, 40, 271-278； J. Med. Chem. [藥物化學雜誌] 2008, 51, 8124-8134； J. Med. Chem. [藥物化學雜誌] 1990, 33, 2697-706； Synthesis[合成] 1989, (5), 396-3977； J. Chem. Soc., Perkin Trans. 1[化學會誌柏爾金彙刊1], 1988, 1663-1668； Tetrahedron[四面體] 1988 44, 3025-3036以及 J. Org. Chem. [有機化學雜誌] 1988 53(6), 1323-1326。 Compounds of formula 1 wherein W is O prepared by the above method can be prepared using various standard sulfurization reagents such as phosphorus pentasulfide or 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4 - Diphosphetane-2,4-disulfide (Lawesson's reagent) is converted to the corresponding thioamide where W is S. Reactions of this type are well known, see e.g. Heterocycles [Heterocyclic Compounds] 1995 , 40 , 271-278; J. Med. Chem . [Journal of Medicinal Chemistry] 2008 , 51 , 8124-8134; J. Med. Chem . [Journal of Medicinal Chemistry] 1990 , 33 , 2697-706; Synthesis [Synthesis] 1989 , (5), 396-3977; J. Chem. Soc., Perkin Trans. 1 [Chemical Society Journal Perkin Trans. 1], 1988 , 1663-1668; Tetrahedron [tetrahedron] 1988 44 , 3025-3036 and J. Org. Chem . [Journal of Organic Chemistry] 1988 53 (6), 1323-1326.
方案1至10示出了製備具有多種取代基的式 1的化合物之方法。具有取代基而不是方案1至10中特別指出的那些取代基的式 1的化合物可以藉由合成有機化學領域中已知的一般方法（包括類似於方案1至10中所述之方法）來製備。 Schemes 1 to 10 illustrate methods for preparing compounds of formula 1 with various substituents. Compounds of Formula 1 having substituents other than those specifically indicated in Schemes 1 to 10 can be prepared by general methods known in the art of synthetic organic chemistry, including methods analogous to those described in Schemes 1 to 10 .
熟悉該項技術者認識到，各種官能基可被轉變成其他以提供不同的式 1的化合物。式 1的化合物或用於其製備的中間體可以含有芳族硝基，其可被還原為胺基，然後經由本領域熟知的反應（例如桑德邁爾反應（Sandmeyer reaction））轉化為各種鹵化物。藉由類似的已知反應，芳族胺（苯胺）可經由重氮鹽轉化為酚，然後可將其烷基化以製備具有烷氧基取代基的式 1的化合物。同樣，經由桑德邁爾反應製備的芳族鹵化物諸如溴化物或碘化物可以與醇在銅催化條件下反應，諸如烏爾曼反應（Ullmann reaction）或其已知的修改，以提供含有烷氧基取代基的式 1的化合物。另外，一些鹵素基團諸如氟或氯可在鹼性條件下用醇置換，以提供含有相應烷氧基取代基的式 1的化合物。含有鹵化物（較佳的是溴化物或碘化物）的式 1的化合物或其先質係用於過渡金屬催化的交叉偶合反應以製備式 1的化合物的特別有用的中間體。該等類型的反應在文獻中有詳細記載；參見例如Tsuji, Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis[過渡金屬試劑和催化劑：有機合成的創新], John Wiley and Sons, Chichester [約翰威立父子出版社, 奇賈斯特], 2002；Tsuji, Palladium in Organic Synthesis[有機合成中的鈀], Springer [施普林格出版社], 2005；以及Miyaura和Buchwald, Cross Coupling Reactions: A Practical Guide[交叉偶合反應：實用指南], 2002以及其中引用的參考文獻。 Those skilled in the art recognize that various functional groups can be transformed into others to provide different compounds of formula 1 . Compounds of formula 1 or intermediates used for their preparation may contain aromatic nitro groups which can be reduced to amine groups and then converted to various halogenated compounds via reactions well known in the art (such as the Sandmeyer reaction). things. By similar known reactions, aromatic amines (anilines) can be converted to phenols via diazonium salts, which can then be alkylated to prepare compounds of formula 1 with alkoxy substituents. Likewise, aromatic halides such as bromides or iodides prepared via the Sandmeyer reaction can be reacted with alcohols under copper-catalyzed conditions, such as the Ullmann reaction or known modifications thereof, to provide A compound of formula 1 having an oxy substituent. Additionally, some halo groups such as fluorine or chlorine can be replaced with alcohols under basic conditions to provide compounds of formula 1 containing the corresponding alkoxy substituents. Compounds of formula 1 or their precursors containing a halide, preferably bromide or iodide, are particularly useful intermediates for transition metal catalyzed cross-coupling reactions to prepare compounds of formula 1 . Reactions of this type are well documented in the literature; see for example Tsuji, Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis [Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis], John Wiley and Sons, Chichester [John Wiley and Sons Publishing House, Chijust], 2002; Tsuji, Palladium in Organic Synthesis [Palladium in Organic Synthesis], Springer [Springer Verlag], 2005; and Miyaura and Buchwald, Cross Coupling Reactions: A Practical Guide [ Cross-Coupling Reactions: A Practical Guide], 2002 and references cited therein.
應認識到，上述對於製備式 1的化合物所描述的某些試劑和反應條件可能不與中間體中存在的某些官能基相容。在該等情況下，將保護/去保護序列或官能基相互轉換結合到合成中將有助於獲得所期望的產物。保護基團的使用和選擇對於化學合成的技術人員來說將是明顯的（參見，例如Greene, T. W.；Wuts, P. G. M. Protective Groups in Organic Synthesis[有機合成中的保護基團], 第2版；Wiley: New York [威利出版社, 紐約], 1991）。熟悉該項技術者將認識到，在一些情況下，在引入各個方案中所述之試劑後，可能需要未詳細描述的另外的常規合成步驟以完成式 1的化合物的合成。熟悉該項技術者還將認識到，可能必需以與製備式 1的化合物所呈現的具體序列不同的順序來進行以上方案中示出的步驟的組合。 It will be recognized that certain reagents and reaction conditions described above for the preparation of compounds of Formula 1 may not be compatible with certain functional groups present in the intermediates. In such cases, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will help to obtain the desired product. The use and choice of protecting groups will be apparent to those skilled in chemical synthesis (see, e.g., Greene, TW; Wuts, PGM Protective Groups in Organic Synthesis [Protecting Groups in Organic Synthesis], 2nd ed.; Wiley : New York [Wiley Press, New York], 1991). Those skilled in the art will recognize that, in some cases, additional routine synthetic steps not described in detail may be required to complete the synthesis of compounds of Formula 1 after introduction of the reagents described in the various schemes. Those skilled in the art will also recognize that it may be necessary to perform combinations of steps shown in the schemes above in an order different from the specific sequence presented for the preparation of compounds of Formula 1 .
熟悉該項技術者還將認識到，本文所述之式 1的化合物和中間體可經受各種親電反應、親核反應、自由基反應、有機金屬反應、氧化反應和還原反應以添加取代基或改性現有的取代基。 Those skilled in the art will also recognize that compounds of Formula 1 and intermediates described herein can be subjected to various electrophilic, nucleophilic, free radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
無需進一步闡述，據信熟悉該項技術者使用先前描述可以最大程度地利用本發明。因此，以下實例應被解釋為僅是說明性的，並且不以任何方式限制本揭露。以下實例中的步驟示出了在整體合成轉化中每個步驟的程序，並且用於每個步驟的起始物質並不必須由其程序描述於其他實例或步驟中的具體製備試驗來製備。百分比係按重量計，除了層析溶劑混合物或另外指明的情況之外。除非另外指明，層析溶劑混合物的份數和百分比係按體積計。 1H NMR譜以四甲基矽烷的低場處的ppm來報告；「s」係指單重峰，「d」係指二重峰，「t」係指三重峰，「m」係指多重峰，「brs」係指寬單重峰，並且「dd」係指雙重雙峰。術語HPLC意指高效液相層析法。術語「pheox」意指苯基㗁唑啉配位基。 Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. Accordingly, the following examples should be construed as merely illustrative, and not limiting of the present disclosure in any way. The steps in the following examples illustrate the procedure for each step in an overall synthetic transformation, and the starting material for each step is not necessarily prepared from specific preparative experiments whose procedures are described in other examples or steps. Percentages are by weight, except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages of chromatographic solvent mixtures are by volume unless otherwise indicated. 1 H NMR spectra are reported in ppm downfield from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "m" means multiplet peak, "brs" refers to a broad singlet, and "dd" refers to a doublet doublet. The term HPLC means high performance liquid chromatography. The term "pheox" means a phenyloxazoline ligand.
實例1Example 1
(1 R,5 R,6 R)- N-(3-甲基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺和(1 S,5 S,6 S)- N-(3-甲基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺的製備。 (1 R ,5 R ,6 R ) -N- (3-methylphenyl)-2-oxabicyclo[3.1.0]hexane-6-formamide and (1 S ,5 S ,6 Preparation of S ) -N- (3-methylphenyl)-2-oxabicyclo[3.1.0]hexane-6-carboxamide.
步驟A： rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸甲酯的製備。 Step A: Preparation of rel -(1 R ,5 R ,6 R )-2-oxabicyclo[3.1.0]hexane-6-carboxylic acid methyl ester.
在室溫下以2 mL/h的速率向乙酸銠(II)二聚體（0.16 g，0.35 mmol）和2,3-二氫呋喃（8 mL，106 mmol）於二氯甲烷（117 mL）中的經攪拌混合物中添加重氮基乙酸乙酯（87%於二氯甲烷中，4.26 mL，35.3 mmol）。將反應混合物攪拌20 min，減壓濃縮並藉由矽膠柱層析法（用在己烷中的0至15%的乙酸乙酯梯度洗脫）純化，得到呈無色液體的非鏡像異構物的3 : 1混合物（4.24 g），其含有作為主要非鏡像異構物的標題化合物。Rhodium(II) acetate dimer (0.16 g, 0.35 mmol) and 2,3-dihydrofuran (8 mL, 106 mmol) were dissolved in dichloromethane (117 mL) at room temperature at a rate of 2 mL/h To the stirred mixture in , was added ethyl diazoacetate (87% in dichloromethane, 4.26 mL, 35.3 mmol). The reaction mixture was stirred for 20 min, concentrated under reduced pressure and purified by silica gel column chromatography (eluting with a gradient of 0 to 15% ethyl acetate in hexanes) to give the diastereomer as a colorless liquid. 3:1 mixture (4.24 g) containing the title compound as the major diastereomer.
1H NMR (CDCl 3, 500 MHz) δ 4.24-4.02 (m, 4H), 3.52-3.43 (m, 0.75H), 2.51-2.42 (m, 0.25H), 2.30-2.22 (m, 0.25H), 2.22-2.14 (m, 1.5H), 2.12-2.07 (m, 0.25H), 2.07-2.01 (m, 0.75H), 1.91-1.87 (m, 1H), 1.60-1.55 (m, 0.25H), 1.30-1.21 (m, 3H)。 1 H NMR (CDCl 3 , 500 MHz) δ 4.24-4.02 (m, 4H), 3.52-3.43 (m, 0.75H), 2.51-2.42 (m, 0.25H), 2.30-2.22 (m, 0.25H), 1.30 -1.21 (m, 3H).
步驟B： rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸的製備。 Step B: Preparation of rel -(1 R ,5 R ,6 R )-2-oxabicyclo[3.1.0]hexane-6-carboxylic acid.
向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸甲酯（即，步驟A的產物）（4.24 g，27.2 mmol）在四氫呋喃（27 mL）和甲醇（13.5 mL）中的溶液中添加氫氧化鋰一水合物（1.37 g，32.6 mmol）在水（13.6 mL）中的溶液並在室溫下攪拌4.5 h。用乙醚（1x）洗滌反應混合物。將水層用鹽酸（1 N水溶液）酸化並用乙酸乙酯（3x）萃取。合併萃取物，用飽和鹽水溶液洗滌，經硫酸鎂乾燥，過濾並減壓濃縮，得到非鏡像異構物的9 : 1混合物（2.47 g），其含有作為主要非鏡像異構物的標題化合物。 Add rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxylate (i.e., the product of Step A) (4.24 g, 27.2 mmol) in THF (27 mL) and methanol (13.5 mL) was added a solution of lithium hydroxide monohydrate (1.37 g, 32.6 mmol) in water (13.6 mL) and stirred at room temperature for 4.5 h. The reaction mixture was washed with diethyl ether (1x). The aqueous layer was acidified with hydrochloric acid (1 N aq) and extracted with ethyl acetate (3x). The combined extracts were washed with saturated brine solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a 9:1 mixture of diastereomers (2.47 g) containing the title compound as the major diastereomer.
1H NMR (DMSO- d 6 , 500 MHz) δ 12.82-10.74 (m, 1H), 4.19-4.14 (m, 0.1H), 4.12-4.01 (m, 0.9H), 4.00-3.89 (m, 1H), 3.47-3.40 (m, 1H), 2.37-2.27 (m, 0.2H), 2.22-2.11 (m, 0.2H), 2.10-1.94 (m, 2.6H), 1.90-1.83 (m, 0.9H), 1.55-1.48 (m, 0.1H)。 1 H NMR (DMSO- d 6 , 500 MHz) δ 12.82-10.74 (m, 1H), 4.19-4.14 (m, 0.1H), 4.12-4.01 (m, 0.9H), 4.00-3.89 (m, 1H) , 3.47-3.40 (m, 1H), 2.37-2.27 (m, 0.2H), 2.22-2.11 (m, 0.2H), 2.10-1.94 (m, 2.6H), 1.90-1.83 (m, 0.9H), 1.55-1.48 (m, 0.1H).
步驟C： rel-(1 R,5 R,6 R)- N-(3-甲基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物41）的製備。 Step C: rel- ( 1R , 5R , 6R ) -N- (3-methylphenyl)-2-oxabicyclo[3.1.0]hexane-6-carboxamide (compound 41) preparation.
在0°C下向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸（即，步驟B的產物）（0.25 g，1.94 mmol）和間甲苯胺（0.21 g，1.94 mmol）在乙酸乙酯（5 mL）中的溶液中添加三乙胺（392 mg，3.88 mmol），然後添加丙基膦酸酐（50%的乙酸乙酯溶液，1.85 g，2.91 mmol）。將反應混合物在環境溫度下攪拌12 h。將反應混合物用水洗滌，然後用飽和鹽水溶液洗滌。將有機萃取物經無水硫酸鈉乾燥，減壓濃縮並藉由矽膠柱層析法（用石油醚中的乙酸乙酯洗脫）純化，得到呈固體的標題化合物，即本發明之化合物（0.20 g）。 rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxylic acid (i.e., the product of Step B) (0.25 g, 1.94 mmol ) and m-toluidine (0.21 g, 1.94 mmol) in ethyl acetate (5 mL) was added triethylamine (392 mg, 3.88 mmol), followed by propylphosphonic anhydride (50% solution in ethyl acetate , 1.85 g, 2.91 mmol). The reaction mixture was stirred at ambient temperature for 12 h. The reaction mixture was washed with water and then with saturated saline solution. The organic extract was dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography (eluted with ethyl acetate in petroleum ether) to give the title compound, the compound of the present invention (0.20 g ).
1H NMR (CDCl 3, 400 MHz) δ 7.35-7.31 (m, 2H), 7.20-7.16 (m, 2H), 6.90 (br s, 1H), 4.28-4.27 (d, 1H), 4.12-4.09 (m, 1H), 3.54-3.49 (m, 1H), 2.32 (s, 3H), 2.31-2.29 (m, 1H), 2.26-2.24 (m, 1H), 2,09-2.07 (m, 1H), 1.83-1.79 (d, 1H)。 1 H NMR (CDCl 3 , 400 MHz) δ 7.35-7.31 (m, 2H), 7.20-7.16 (m, 2H), 6.90 (br s, 1H), 4.28-4.27 (d, 1H), 4.12-4.09 ( m, 1H), 3.54-3.49 (m, 1H), 2.32 (s, 3H), 2.31-2.29 (m, 1H), 2.26-2.24 (m, 1H), 2,09-2.07 (m, 1H), 1.83-1.79 (d, 1H).
LCMS: m/z: 218 [M+H] + LCMS: m/z: 218 [M+H] +
步驟D： (1 R,5 R,6 R)- N-(3-甲基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺和(1 S,5 S,6 S)- N-(3-甲基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺的製備。 Step D: (1 R ,5 R ,6 R ) -N- (3-methylphenyl)-2-oxabicyclo[3.1.0]hexane-6-carboxamide and (1 S ,5 Preparation of S ,6 S ) -N- (3-methylphenyl)-2-oxabicyclo[3.1.0]hexane-6-carboxamide.
將 rel-(1 R,5 R,6 R)- N-(3-甲基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺的鏡像異構物（即，步驟C的產物）藉由超臨界流體層析製備型HPLC（在Chiracel OX-H柱上用40%甲醇/CO 2洗脫，3 mL/min，在35°C下）分離，得到較快洗脫的呈白色半固體的鏡像異構物（化合物85），即本發明之化合物，其具有99.6%的鏡像異構物過量和[α] D 20+66.8°的旋光度（濃度=0.50，在甲醇中）。 The enantiomer ( _ _ That is, the product of step C) was separated by supercritical fluid chromatography preparative HPLC ( eluting with 40% methanol/CO on a Chiracel OX-H column, 3 mL/min at 35°C) to give comparative The fast-eluting enantiomer (compound 85) as a white semi-solid, a compound of the invention, has an enantiomer excess of 99.6% and an optical rotation of [α] D 20 +66.8° (concentration=0.50 , in methanol).
較慢洗脫的鏡像異構物（化合物84）（也是本發明之化合物）分離為白色半固體，其具有99.6%的鏡像異構物過量和[α] D 20-62.8°的旋光度（濃度=0.50，在甲醇中）。 The slower eluting enantiomer (compound 84), also a compound of the invention, was isolated as a white semisolid with a 99.6% enantiomer excess and an optical rotation of [α] D 20 −62.8° (concentration =0.50 in methanol).
實例2Example 2
rel-(1 R,5 R,6 R)- N-(1,2-二氫-1-甲基-2-側氧基-3-吡啶基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物51）的製備。 rel -(1 R ,5 R ,6 R ) -N- (1,2-dihydro-1-methyl-2-oxo-3-pyridyl)-2-oxabicyclo[3.1.0 ] Preparation of hexane-6-carboxamide (Compound 51).
在0°C下向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸（即，實例1步驟B的產物）（250 mg，1.94 mmol）和3-胺基-1-甲基吡啶-2(1 H)-酮（204 mg，1.94 mmol）在乙酸乙酯（5 mL）中的溶液中添加三乙胺（392 mg，3.88 mmol），然後添加丙基膦酸酐（50%的乙酸乙酯溶液，1.85 g，2.91 mmol），並在環境溫度下攪拌12 h。將反應混合物用水洗滌，然後用飽和鹽水溶液洗滌。將有機萃取物經無水硫酸鈉乾燥，減壓濃縮並藉由矽膠柱層析法（用石油醚中乙酸乙酯洗脫）純化，得到呈半固體的標題化合物，即本發明之化合物（120 mg）。 rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxylic acid (i.e., the product of Example 1 step B) (250 mg, 1.94 mmol) and 3-amino-1-methylpyridin-2( 1H )-one (204 mg, 1.94 mmol) in ethyl acetate (5 mL) was added triethylamine (392 mg, 3.88 mmol), then propylphosphonic anhydride (50% in ethyl acetate, 1.85 g, 2.91 mmol) was added and stirred at ambient temperature for 12 h. The reaction mixture was washed with water and then with saturated saline solution. The organic extract was dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography (eluted with ethyl acetate in petroleum ether) to obtain the title compound, the compound of the present invention (120 mg ).
1H NMR (CDCl 3, 400 MHz) δ 8.53 (br s, 1H), 8.28-8.26 (d, 1H), 7.00-6.90 (d, 1H), 6.24-6.20 (t, 1H), 4.28-4.27 (d, 1H), 4.15-4.11 (m, 1H), 3.64 (s, 3H), 3.56-3.54 (m, 1H), 2.32-2.22 (m, 2H), 2.11-2.06 (m, 1H), 1.95-1.94 (d, 1H)。 1 H NMR (CDCl 3 , 400 MHz) δ 8.53 (br s, 1H), 8.28-8.26 (d, 1H), 7.00-6.90 (d, 1H), 6.24-6.20 (t, 1H), 4.28-4.27 ( d, 1H), 4.15-4.11 (m, 1H), 3.64 (s, 3H), 3.56-3.54 (m, 1H), 2.32-2.22 (m, 2H), 2.11-2.06 (m, 1H), 1.95- 1.94 (d, 1H).
LCMS: m/z: 235.1 [M+H] +。 LCMS: m/z: 235.1 [M+H] + .
實例3Example 3
rel-(1 R,5 R,6 R)- N-(1-甲基-1 H-吡唑-3-基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物55）的製備。 rel -(1 R ,5 R ,6 R ) -N -(1-methyl-1 H -pyrazol-3-yl)-2-oxabicyclo[3.1.0]hexane-6-formyl Preparation of Amine (Compound 55).
在0°C下向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸（即，實例1步驟B的產物）（0.25 g，1.94 mmol）和3-胺基-1-甲基吡唑（0.19 g，1.94 mmol）在乙酸乙酯（10 mL）中的溶液中添加三乙胺（392 mg，3.88 mmol），然後添加丙基膦酸酐（50%的乙酸乙酯溶液，1.85 g，2.91 mmol），並在環境溫度下攪拌12 h。將反應混合物用水洗滌，然後用飽和鹽水溶液洗滌。將有機萃取物經無水硫酸鈉乾燥，減壓濃縮並藉由矽膠柱層析法（用石油醚中乙酸乙酯洗脫）純化，得到呈固體的標題化合物，即本發明之化合物（150 mg）。 rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxylic acid (i.e., the product of step B of Example 1) (0.25 g, 1.94 mmol) and 3-amino-1-methylpyrazole (0.19 g, 1.94 mmol) in ethyl acetate (10 mL) were added triethylamine (392 mg, 3.88 mmol) followed by propyl Phosphonic anhydride (50% in ethyl acetate, 1.85 g, 2.91 mmol) and stirred at ambient temperature for 12 h. The reaction mixture was washed with water and then with saturated saline solution. The organic extract was dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography (eluted with ethyl acetate in petroleum ether) to give the title compound, the compound of the present invention, as a solid (150 mg) .
1H NMR (DMSO- d 6 , 500 MHz) δ 10.43 (s, 1H), 7.50-7.49 (d, 1H), 6.35 (d,1H), 4.02-3.96 (m, 2H), 3.71 (s, 3H), 2.14 (d,1H), 2.08-1.97 (m,3H)。 1 H NMR (DMSO- d 6 , 500 MHz) δ 10.43 (s, 1H), 7.50-7.49 (d, 1H), 6.35 (d, 1H), 4.02-3.96 (m, 2H), 3.71 (s, 3H ), 2.14 (d,1H), 2.08-1.97 (m,3H).
LCMS: m/z: 209.1 [M+H] +。 LCMS: m/z: 209.1 [M+H] + .
實例4Example 4
rel-(1 R,5 R,6 R)- N-[2-[(甲基胺基)羰基]苯基]-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物2）的製備。 rel -(1 R ,5 R ,6 R ) -N -[2-[(methylamino)carbonyl]phenyl]-2-oxabicyclo[3.1.0]hexane-6-formamide (Compound 2) Preparation.
向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲酸（即，實例1步驟B的產物）（100 mg，0.78 mmol）和 O-(7-氮雜苯并三唑-1-基)- N,N,N',N'-四甲基脲鎓六氟磷酸鹽（HATU）（326 mg，0.86 mmol）在DMF（0.5 mL）中的溶液中添加2-胺基- N-甲基-苯甲醯胺（114 μL，0.86 mmol），然後添加 N, N-二異丙基乙胺（0.34 mL，1.95 mmol）。在室溫下攪拌反應混合物過夜。將反應混合物用乙酸乙酯稀釋，用鹽水洗滌，經無水硫酸鈉乾燥，過濾，減壓濃縮並藉由矽膠柱層析法（用己烷中10%至70%的乙酸乙酯梯度洗脫）純化，得到呈固體的標題化合物，即本發明之化合物（86 mg）。 To rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxylic acid (i.e., the product of step B of Example 1) (100 mg, 0.78 mmol) and O -(7-Azabenzotriazol-1-yl) -N,N,N',N' -tetramethyluronium hexafluorophosphate (HATU) (326 mg, 0.86 mmol) in DMF (0.5 mL ) was added 2-amino- N -methyl-benzamide (114 μL, 0.86 mmol), followed by N , N -diisopropylethylamine (0.34 mL, 1.95 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure and purified by silica gel column chromatography (gradient elution with 10% to 70% ethyl acetate in hexane) Purification afforded the title compound, the compound of the invention (86 mg) as a solid.
1H NMR (丙酮- d 6 , 500 MHz) δ 11.84-11.61 (m, 1H), 8.64 - 8.53 (m, 1H), 8.13-7.88 (m, 1H), 7.78-7.69 (m, 1H), 7.50-7.40 (m, 1H), 7.11-7.01 (m, 1H), 4.16-3.97 (m, 2H), 3.67-3.55 (m, 1H), 2.96-2.92 (m, 3H), 2.19-2.12 (m, 3H), 2.01-1.98 (m, 1H)。 1 H NMR (acetone- d 6 , 500 MHz) δ 11.84-11.61 (m, 1H), 8.64 - 8.53 (m, 1H), 8.13-7.88 (m, 1H), 7.78-7.69 (m, 1H), 7.50 -7.40 (m, 1H), 7.11-7.01 (m, 1H), 4.16-3.97 (m, 2H), 3.67-3.55 (m, 1H), 2.96-2.92 (m, 3H), 2.19-2.12 (m, 3H), 2.01-1.98 (m, 1H).
實例5Example 5
rel-(1 R,5 R,6 R)- N-(5-氟-2-甲氧基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物222）的製備。 rel -(1 R ,5 R ,6 R ) -N- (5-fluoro-2-methoxyphenyl)-2-oxabicyclo[3.1.0]hexane-6-formamide (compound 222) preparation.
步驟A： rel-(1 R,5 R,6 R)-[2-氧雜二環[3.1.0]己烷-6-甲酸1,3-二側氧基異吲哚-2-基酯]的製備。 Step A: rel -(1 R ,5 R ,6 R )-[2-oxabicyclo[3.1.0]hexane-6-carboxylic acid 1,3-dioxoisoindol-2-yl ester ] preparation.
在乾燥氮氣氛下，向(乙腈)[2-(4,5-二氫-4,4-二甲基-2-㗁唑基-κ N 3)苯基-κ C][(1,2,3,4,5,6-η)-1-甲基-4-(1-甲基乙基)苯]-釕(1+)六氟磷酸鹽(1-)（1 : 1）（即CAS 1219034-15-7）（其製備參見 Organometallics[有機金屬化合物] 2010, 29, 1413-1420）（57 mg，0.096 mmol）中添加二氯甲烷（60 mL）和2,3-二氫呋喃（3.63 mL，48.0 mmol）並冷卻至0°C。將2-重氮基乙酸1,3-二側氧基異吲哚-2-基酯（其製備參見 Angew. Chem. Int. Ed. [應用化學國際版] 2019, 58, 5930）（2.22 g，9.60 mmol）在二氯甲烷（31 mL）中的溶液逐滴添加到混合物中並在0°C下攪拌30 min。將反應混合物減壓濃縮並藉由矽膠柱層析法（用己烷中10%至40%的乙酸乙酯梯度洗脫）純化，得到非鏡像異構物的10 : 1混合物（2.42 g），其含有作為主要非鏡像異構物的標題化合物。 Under dry nitrogen atmosphere, to (acetonitrile)[2-(4,5-dihydro-4,4-dimethyl-2-oxazolyl-κ N 3 )phenyl-κ C ][(1,2 ,3,4,5,6-η)-1-methyl-4-(1-methylethyl)benzene]-ruthenium (1+) hexafluorophosphate (1-) (1 : 1) (ie CAS 1219034-15-7) (see Organometallics [Organometallic Compounds] 2010 , 29 , 1413-1420 for its preparation) (57 mg, 0.096 mmol) was added dichloromethane (60 mL) and 2,3-dihydrofuran ( 3.63 mL, 48.0 mmol) and cooled to 0°C. 1,3-Dioxoisoindol-2-yl 2-diazoacetate (see Angew. Chem. Int. Ed . [International Edition of Applied Chemistry] 2019 , 58 , 5930 for its preparation) (2.22 g , 9.60 mmol) in dichloromethane (31 mL) was added dropwise to the mixture and stirred at 0 °C for 30 min. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (gradient elution with 10% to 40% ethyl acetate in hexanes) to give a 10:1 mixture of diastereomers (2.42 g), It contains the title compound as the major diastereomer.
1H NMR (CDCl 3, 500 MHz) δ 7.92-7.85 (m, 2H), 7.82-7.76 (m, 2H), 4.44 (dd, 1H), 4.19-4.11 (m, 1H), 3.61-3.52 (m, 1H), 2.46-2.41 (m, 1H), 2.32-2.15 (m, 3H)。 1 H NMR (CDCl 3 , 500 MHz) δ 7.92-7.85 (m, 2H), 7.82-7.76 (m, 2H), 4.44 (dd, 1H), 4.19-4.11 (m, 1H), 3.61-3.52 (m , 1H), 2.46-2.41 (m, 1H), 2.32-2.15 (m, 3H).
步驟B： rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物221）的製備。 Step B: Preparation of rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxamide (Compound 221).
在乾燥氮氣氛下向 rel-(1 R,5 R,6 R)-[2-氧雜二環[3.1.0]己烷-6-甲酸1,3-二側氧基異吲哚-2-基酯]（即，實例5步驟A的產物）（100 mg，0.36 mmol）中添加氨（0.4 M的四氫呋喃溶液，4.6 mL，1.83 mmol）並在室溫下攪拌過夜。將反應混合物藉由Celite ®矽藻土助濾劑過濾，用乙酸乙酯洗滌並減壓濃縮，得到呈固體的標題化合物（46 mg）。 Under a dry nitrogen atmosphere -yl ester] (ie, the product of Step A of Example 5) (100 mg, 0.36 mmol) was added ammonia (0.4 M in THF, 4.6 mL, 1.83 mmol) and stirred overnight at room temperature. The reaction mixture was filtered through Celite® filter aid, washed with ethyl acetate and concentrated under reduced pressure to give the title compound (46 mg) as a solid.
1H NMR (CDCl 3, 500 MHz) δ 5.66-5.11 (m, 2H), 4.23-4.18 (m, 1H), 4.13-4.04 (m, 1H), 3.55-3.45 (m, 1H), 2.27-2.14 (m, 2H), 2.10-1.98 (m, 1H), 1.74-1.68 (m, 1H)。 1 H NMR (CDCl 3 , 500 MHz) δ 5.66-5.11 (m, 2H), 4.23-4.18 (m, 1H), 4.13-4.04 (m, 1H), 3.55-3.45 (m, 1H), 2.27-2.14 (m, 2H), 2.10-1.98 (m, 1H), 1.74-1.68 (m, 1H).
步驟C： rel-(1 R,5 R,6 R)- N-(5-氟-2-甲氧基苯基)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物222）的製備。 Step C: rel -(1 R ,5 R ,6 R ) -N- (5-fluoro-2-methoxyphenyl)-2-oxabicyclo[3.1.0]hexane-6-formyl Preparation of Amine (Compound 222).
在乾燥氮氣氛下，向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（即，實例5步驟B的產物）（127 mg，1.0 mmol）、磷酸三鉀（297 mg，1.40 mmol）和烯丙基[2-(二三級丁基膦基)-2′,4′,6′-三異丙基-3,6-二甲氧基-1,1′-聯苯基)]三氟甲磺酸鈀(II)（即[(烯丙基)Pd(tBuBrettPhos)]OTf）（16 mg，0.02 mmol）中添加2-氯-4-氟-1-甲氧基苯（0.19 g，1.2 mmol），然後添加三級丁醇（2.0 mL），並在110°C下攪拌90分鐘。將反應混合物用二氯甲烷稀釋，減壓濃縮並藉由矽膠柱層析法（用己烷中10%至50%的乙酸乙酯梯度洗脫）純化，得到呈固體的標題化合物，即本發明之化合物（174 mg）。 Under a dry nitrogen atmosphere, rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxamide (i.e., the product of step B of Example 5) ( 127 mg, 1.0 mmol), tripotassium phosphate (297 mg, 1.40 mmol) and allyl[2-(ditertiary butylphosphino)-2′,4′,6′-triisopropyl-3, 6-Dimethoxy-1,1′-biphenyl)]palladium(II)trifluoromethanesulfonate (i.e. [(allyl)Pd(tBuBrettPhos)]OTf) (16 mg, 0.02 mmol) was added 2-Chloro-4-fluoro-1-methoxybenzene (0.19 g, 1.2 mmol), then added tert-butanol (2.0 mL), and stirred at 110 °C for 90 min. The reaction mixture was diluted with dichloromethane, concentrated under reduced pressure and purified by silica gel column chromatography (gradient elution with 10% to 50% ethyl acetate in hexane) to obtain the title compound as a solid, i.e. the present invention compound (174 mg).
1H NMR (CDCl 3, 500 MHz) δ 8.13 (dd, 7.89 (br s, 1H), 6.83-6.74 (m, 1H), 6.73-6.65 (m, 1H), 4.31-4.25 (m, 1H), 4.16-4.09 (m, 1H), 3.90-3.87 (m, 3H), 3.59-3.51 (m, 1H), 2.33 (d, J= 3.78 Hz, 1H), 2.29-2.20 (m, 1H), 2.11-2.05 (m, 1H), 1.86-1.82 (m, 1H)。 1 H NMR (CDCl 3 , 500 MHz) δ 8.13 (dd, 7.89 (br s, 1H), 6.83-6.74 (m, 1H), 6.73-6.65 (m, 1H), 4.31-4.25 (m, 1H), 4.16-4.09 (m, 1H), 3.90-3.87 (m, 3H), 3.59-3.51 (m, 1H), 2.33 (d, J = 3.78 Hz, 1H), 2.29-2.20 (m, 1H), 2.11- 2.05 (m, 1H), 1.86-1.82 (m, 1H).
LCMS: m/z: 252.2 [M+H] +。 LCMS: m/z: 252.2 [M+H] + .
實例6Example 6
rel-(1 R,5 R,6 R)- N-[5-氯-2-(甲基胺基甲醯基)苯基]-2-氧雜二環[3.1.0]己烷-6-甲醯胺（化合物173）的製備。 rel -(1 R ,5 R ,6 R ) -N -[5-chloro-2-(methylaminoformyl)phenyl]-2-oxabicyclo[3.1.0]hexane-6 - Preparation of formamide (compound 173).
在乾燥氮氣氛下，向 rel-(1 R,5 R,6 R)-2-氧雜二環[3.1.0]己烷-6-甲醯胺（即，實例5步驟B的產物）（75 mg，0.59 mmol）、4-氯-2-碘- N-甲基苯甲醯胺（145 mg，0.49 mmol）、磷酸三鉀（0.21 g，0.98 mmol）和碘化亞銅(I)（4.7 mg，0.025 mmol）中添加( 反式)- N, N′-二甲基-1,2-環己烷二胺（7.0 mg，0.049 mmol），然後添加 N, N-二甲基甲醯胺（0.49 mL），並在50°C下攪拌40 h。將反應混合物用乙酸乙酯稀釋，用水洗滌，經無水硫酸鎂乾燥，過濾，減壓濃縮並藉由矽膠柱層析法（用己烷中30%至80%的乙酸乙酯梯度洗脫）純化，得到呈固體的標題化合物，即本發明之化合物（56 mg）。 Under a dry nitrogen atmosphere, rel- ( 1R , 5R , 6R )-2-oxabicyclo[3.1.0]hexane-6-carboxamide (i.e., the product of step B of Example 5) ( 75 mg, 0.59 mmol), 4-chloro-2-iodo- N -methylbenzamide (145 mg, 0.49 mmol), tripotassium phosphate (0.21 g, 0.98 mmol) and cuprous(I) iodide ( (4.7 mg, 0.025 mmol) was added to ( trans ) -N , N′ -dimethyl-1,2-cyclohexanediamine (7.0 mg, 0.049 mmol), followed by the addition of N , N -dimethylformyl amine (0.49 mL) and stirred at 50 °C for 40 h. The reaction mixture was diluted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by silica gel column chromatography (gradient elution with 30% to 80% ethyl acetate in hexanes) , to give the title compound, the compound of the present invention (56 mg) as a solid.
1H NMR (CDCl 3, 500 MHz) δ 11.33 (br s, 1H), 8.68-8.63 (m, 1H), 7.36-7.33 (m, 1H), 7.03-6.98 (m, 1 H), 6.30-6.14 (m, 1H), 4.29-4.24 (m, 1H), 4.14-4.07 (m, 1H), 3.57-3.49 (m, 1H), 3.01 (d, 3H), 2.31-2.26 (m, 1H), 2.26-2.18 (m, 1H), 2.11-2.05 (m, 1H), 1.92-1.88 (m, 1H)。 1 H NMR (CDCl 3 , 500 MHz) δ 11.33 (br s, 1H), 8.68-8.63 (m, 1H), 7.36-7.33 (m, 1H), 7.03-6.98 (m, 1 H), 6.30-6.14 (m, 1H), 4.29-4.24 (m, 1H), 4.14-4.07 (m, 1H), 3.57-3.49 (m, 1H), 3.01 (d, 3H), 2.31-2.26 (m, 1H), 2.26 -2.18 (m, 1H), 2.11-2.05 (m, 1H), 1.92-1.88 (m, 1H).
LCMS: m/z: 252.2 [M-H] -。 LCMS: m/z: 252.2 [MH] - .
實例7Example 7
rel-(1 R,5 R,6 R)-[2-氧雜二環[3.1.0]己烷-6-甲酸1,3-二側氧基異吲哚-2-基酯]的單一鏡像異構物的手性製備。 rel- (1 R ,5 R ,6 R )-[2-oxabicyclo[3.1.0]hexane-6-carboxylic acid 1,3-dioxoisoindol-2-yl ester] Chiral Preparation of Mirror Isomers.
步驟A： [(對傘花烴)Ru(( S)-Pheox)(MeCN)]PF 6的製備。 Step A: Preparation of [(p-cymene)Ru(( S )-Pheox)(MeCN)]PF 6 .
在室溫下向(4 S)-4,5-二氫-2,4-二苯基㗁唑（0.5 g，2.2 mmol）在乙腈（50 mL）中的溶液中添加氫氧化鈉（1 M水溶液，90 mg，2.2 mmol）和六氟磷酸鉀（1.64 g，8.9 mmol）並用氮氣鼓泡10 min。將二氯(對傘花烴)釕(II)二聚體（683 mg，1.12 mmol）添加到反應混合物中，在80°C下攪拌16 h，減壓濃縮並且藉由矽膠柱層析法（用二氯甲烷中3%乙腈洗脫）純化，得到呈固體的標題化合物的異構物的混合物（0.3 g）。 To a solution of ( 4S )-4,5-dihydro-2,4-diphenyloxazole (0.5 g, 2.2 mmol) in acetonitrile (50 mL) was added sodium hydroxide (1 M aqueous solution, 90 mg, 2.2 mmol) and potassium hexafluorophosphate (1.64 g, 8.9 mmol) and bubbled with nitrogen for 10 min. Dichloro(p-cymene)ruthenium(II) dimer (683 mg, 1.12 mmol) was added to the reaction mixture, stirred at 80°C for 16 h, concentrated under reduced pressure and analyzed by silica gel column chromatography ( Purification (eluting with 3% acetonitrile in dichloromethane) gave a mixture of isomers of the title compound as a solid (0.3 g).
1H NMR (CDCl 3, 400 MHz) δ 8.02-7.95 (m, 1H), 7.61-7.31 (m, 6H), 7.30-7.22 (m, 1H), 7.15-7.09 (m, 1H), 5.77-5.68 (m, 1H), 5.55-5.40 (m, 2H), 5.30-5.12 (m, 2H), 4.80-4.70 (m, 1H), 4.62-4.60 (m, 0.5H), 4.22-4.20 (m, 0.5H), 2.35-2.20 (m, 1H), 2.28 (s, 1.5 H), 2.00 (s, 3H), 1.81 (s, 1.5 H), 1.00-0.70 (m, 6H)。 1 H NMR (CDCl 3 , 400 MHz) δ 8.02-7.95 (m, 1H), 7.61-7.31 (m, 6H), 7.30-7.22 (m, 1H), 7.15-7.09 (m, 1H), 5.77-5.68 (m, 1H), 5.55-5.40 (m, 2H), 5.30-5.12 (m, 2H), 4.80-4.70 (m, 1H), 4.62-4.60 (m, 0.5H), 4.22-4.20 (m, 0.5 H), 2.35-2.20 (m, 1H), 2.28 (s, 1.5H), 2.00 (s, 3H), 1.81 (s, 1.5H), 1.00-0.70 (m, 6H).
步驟B： rel-(1 R,5 R,6 R)-[2-氧雜二環[3.1.0]己烷-6-甲酸1,3-二側氧基異吲哚-2-基酯]的單一鏡像異構物的手性製備。 Step B: rel -(1 R ,5 R ,6 R )-[2-oxabicyclo[3.1.0]hexane-6-carboxylic acid 1,3-dioxoisoindol-2-yl ester ] chiral preparation of a single enantiomer.
在0°C下將2,3-二氫呋喃（0.758.6 g，10.822 mmol，5.0當量）在甲苯（20 mL）中的溶液用氮氣鼓泡10 min，然後添加[(對傘花烴)Ru(( S)-Pheox)(MeCN)]PF 6（即，實例7步驟A的產物）（28 mg，0.043 mmol）。在0°C下在50 min的時間段內添加甲苯（8 mL）中的2-重氮基乙酸1,3-二側氧基異吲哚-2-基酯（其製備參見 Angew. Chem. Int. Ed. [應用化學國際版] 2019, 58, 5930）（0.5 g，2.2 mmol），攪拌5 h。將所得混合物減壓濃縮並藉由矽膠柱層析法（用石油醚中15%的乙酸乙酯梯度洗脫）純化，得到呈固體的標題化合物的鏡像異構物（0.20 g），其具有62%的鏡像異構物過量。 A solution of 2,3-dihydrofuran (0.758.6 g, 10.822 mmol, 5.0 equiv) in toluene (20 mL) was bubbled with nitrogen for 10 min at 0 °C, then [(p-cymene) was added Ru(( S )-Pheox)(MeCN)] PF6 (ie, the product of Example 7, Step A) (28 mg, 0.043 mmol). 1,3-Dioxoisoindol-2-yl 2-diazoacetate (for its preparation see Angew. Chem. Int. Ed . [International Edition of Applied Chemistry] 2019 , 58 , 5930) (0.5 g, 2.2 mmol), stirred for 5 h. The resulting mixture was concentrated under reduced pressure and purified by silica gel column chromatography (gradient elution with 15% ethyl acetate in petroleum ether) to give the enantiomer of the title compound (0.20 g) as a solid with 62 % enantiomer excess.
1H NMR (CDCl 3, 400 MHz) δ 7.91-7.85 (m, 2H), 7.81-7.75 (m, 2H), 4.46-4.41 (m, 1H), 4.19-4.10 (m, 1H), 3.61-3.52 (m, 1H), 2.45-2.40 (m, 1H), 2.30-2.16 (m, 3H)。 1 H NMR (CDCl 3 , 400 MHz) δ 7.91-7.85 (m, 2H), 7.81-7.75 (m, 2H), 4.46-4.41 (m, 1H), 4.19-4.10 (m, 1H), 3.61-3.52 (m, 1H), 2.45-2.40 (m, 1H), 2.30-2.16 (m, 3H).
無需進一步詳盡說明，據信熟悉該項技術者使用前述說明可將本揭露利用至其最大程度。Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present disclosure to its fullest extent.
藉由本文所描述的程序與本領域已知之方法一起，可以製備表1至205中的下列化合物。以下縮寫用於隨後的表中：Me意指甲基，OMe意指甲氧基，Et意指乙基，OEt意指乙氧基， n-Pr意指正丙基， i-Pr意指異丙基， c-Pr意指環丙基， n-Bu意指正丁基， s-Bu意指二級丁基， t-Bu意指三級丁基， c-Bu意指環丁基，Ph意指苯基，並且CN意指氰基。在表1至205中，T具有以下如示例4中所定義的含義。值得注意的T值係其中T選自T-2和T-3。 The following compounds in Tables 1 to 205 could be prepared by the procedures described herein together with methods known in the art. The following abbreviations are used in the tables that follow: Me means methyl, OMe means methoxy, Et means ethyl, OEt means ethoxy, n -Pr means n-propyl, i -Pr means isopropyl , c -Pr means cyclopropyl, n -Bu means n-butyl, s -Bu means secondary butyl, t -Bu means tertiary butyl, c -Bu means cyclobutyl, Ph means phenyl , and CN means cyano. In Tables 1 to 205, T has the meaning as defined in Example 4 below. Notable T values are where T is selected from T-2 and T-3.
示例4
[表1]
本揭露還包括表2至10，除了表1中的行標題（即「T係T-1並且Y係H」）被替換為下文所示的相應行標題之外，每個表的構造與上表1相同。
[表11]
在表11中，在每端上帶有連接號的所列部分（即-CH
2CH
2CH
2CH
2-）表示下述環：其中R
17和R
18連同它們所附接的氮一起形成具有所述部分的環。
本揭露還包括表12至60，除了表11中的行標題（即「T係T-1、R
JC-A係H、R
JC-B係H、R
JC-C係H、R
JC-D係H並且Y係H。」）被替換為下文所示的相應行標題之外，每個表的構造與上表11相同。
[表61]
本揭露還包括表62至145，除了表61中的行標題（即「T係T-1、R
JC-A係H、R
JC-B係H、R
JC-C係H並且Y係H。」）被替換為下文所示的相應行標題之外，每個表的構造與上表61相同。
[表146]
本揭露還包括表147至155，除了表146中的行標題（即「T係T-1並且Y係H」）被替換為下文所示的相應行標題之外，每個表的構造與上表146相同。
[表156]
除了表146中的結構被替換為以上表156的結構外，表156的構造與表146相同。Table 156 is constructed identically to Table 146, except that the structure in Table 146 is replaced with that of Table 156 above.
表157至表165Form 157 to Form 165
除了表147中的結構被替換為以上表157的結構外，表157的構造與表147相同。表158至165以與表148至D-155相同的方式構造。Table 157 is constructed identically to Table 147, except that the structure in Table 147 is replaced with that of Table 157 above. Tables 158 to 165 are constructed in the same manner as Tables 148 to D-155.
[表166]
本揭露還包括表167至175，除了表166中的行標題（即「T係T-1並且Y係H」）被替換為下文所示的相應行標題之外，每個表的構造與上表166相同。
[表176]
除了表166中的結構被替換為以上表176的結構外，表176的構造與表166相同。Table 176 is constructed identically to Table 166, except that the structure in Table 166 is replaced with that of Table 176 above.
表177至表185Form 177 to Form 185
除了表167中的結構被替換為以上表177的結構外，表177的構造與表167相同。表178至185以與表168至175相同的方式構造。Table 177 is constructed identically to Table 167, except that the structure in Table 167 is replaced with that of Table 177 above. Tables 178 to 185 are constructed in the same manner as Tables 168 to 175.
表186
除了表166中的結構被替換為以上表186的結構外，表186的構造與表166相同。Table 186 is constructed identically to Table 166, except that the structure in Table 166 is replaced with that of Table 186 above.
表187至表195Form 187 to Form 195
除了表167中的結構被替換為以上表187的結構外，表187的構造與表167相同。表188至195以與表168至175相同的方式構造。Table 187 is constructed identically to Table 167, except that the structure in Table 167 is replaced with that of Table 187 above. Tables 188 to 195 are constructed in the same manner as Tables 168 to 175.
[表196]
本揭露還包括表197至205，除了表196中的行標題（即「T係T-1並且Y係H」）被替換為下文所示的相應行標題之外，每個表的構造與上表196相同。
製劑/實用性Formulation/Availability
本揭露之化合物一般將用作組成物（即製劑）中的無脊椎害蟲防治活性成分，其中至少一種選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組的附加組分，用作載體。選擇該製劑或組成物成分，以與活性成分的物理特性、施加模式和環境因素諸如土壤類型、水分和溫度一致。The compounds of the present disclosure will generally be used as active ingredients for controlling invertebrate pests in compositions (i.e. formulations), wherein at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, used as carrier. The formulation or composition ingredients are selected to be consistent with the physical characteristics of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
有用的製劑包括液體和固體組成物二者。液體組成物包括視需要可以被稠化成凝膠的溶液（包括可乳化的濃縮物）、懸浮液、乳液（包括微乳液、水包油乳液、可流動的濃縮物和/或懸浮乳液）等。水性液體組成物的一般類型為可溶性濃縮物、懸浮液濃縮物、膠囊懸浮液、濃縮乳液、微乳液、水包油乳液、可流動的濃縮物和懸浮乳液。非水性液體組成物的一般類型為可乳化的濃縮物、可微乳化的濃縮物、可分散的濃縮物和油分散體。Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions, oil-in-water emulsions, flowable concentrates and/or suspoemulsions), etc., which may optionally be thickened into gels. The general types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions, oil-in-water emulsions, flowable concentrates and suspoemulsions. The general types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsifiable concentrates, dispersible concentrates and oil dispersions.
固體組成物的一般類型為粉劑、粉末、顆粒劑、球劑、粒料、錠劑、片劑、填充膜（包括種子包衣）等，它們可以是水可分散的（「可潤濕的」）或水溶性的。由成膜溶液或可流動的懸浮液形成的膜和包衣特別可用於種子處理。活性成分可以被（微）包封並進一步形成為懸浮液或固體製劑；替代性地，活性成分的整個製劑可以被包封（或「包覆」）。包封可以控制或延遲活性成分的釋放。可乳化的顆粒劑結合了可乳化的濃縮物製劑和乾顆粒製劑兩者的優點。高強度組成物主要用作進一步製劑的中間體。The general types of solid compositions are dusts, powders, granules, pellets, pellets, lozenges, tablets, filled films (including seed coatings), etc., which may be water-dispersible ("wettable" ) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively, the entire formulation of the active ingredient can be encapsulated (or "coated"). Encapsulation can control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrate formulations and dry granule formulations. High-strength compositions are mainly used as intermediates for further formulations.
可噴霧的製劑典型地在噴霧之前分散在合適的介質中。此類液體和固體製劑被配製成在噴霧介質，通常為水，但偶爾係另一種合適介質像芳族烴或石蠟烴或植物油中易於稀釋的。噴霧容量的範圍可以為每公頃從約一升至幾千升，但更典型地為在每公頃從約十至幾百升的範圍內。可噴霧的製劑可在槽中與水或另一種合適的介質混合，用於藉由空氣或地面施加來進行葉處理，或用於施加到植株的生長介質中。液體和乾製劑可以直接計量加入滴灌系統中，或在種植期間計量加入壟溝中。液體和固體製劑可在種植之前作為種子處理施加到作物和其他期望的植被的種子，以藉由內吸吸收保護發育中的根和其他地面下的植株部分和/或葉子。Sprayable formulations are typically dispersed in a suitable medium prior to spraying. Such liquid and solid preparations are formulated so as to be readily diluted in a spray medium, usually water, but occasionally another suitable medium like an aromatic or paraffinic hydrocarbon or vegetable oil. Spray volumes may range from about one liter to several thousand liters per hectare, but more typically range from about ten to several hundred liters per hectare. Sprayable formulations may be tank mixed with water or another suitable medium for foliar treatment by air or ground application, or for application to the growing medium of plants. Liquid and dry formulations can be metered directly into drip irrigation systems, or into furrows during planting. Liquid and solid formulations can be applied as seed treatments to the seeds of crops and other desired vegetation prior to planting to protect developing roots and other subterranean plant parts and/or foliage by systemic uptake.
製劑典型地將含有總計達100重量百分比的在以下近似範圍內的有效量的活性成分、稀釋劑和表面活性劑。
固體稀釋劑包括，例如，黏土諸如膨潤土、蒙脫土、凹凸棒石和高嶺土、石膏、纖維素、二氧化鈦、氧化鋅、澱粉、糊精、糖（例如，乳糖、蔗糖）、二氧化矽、滑石、雲母、矽藻土、脲、碳酸鈣、碳酸鈉和碳酸氫鈉，以及硫酸鈉。典型的固體稀釋劑在Watkins等人, Handbook of Insecticide Dust Diluents and Carriers[殺昆蟲劑粉劑稀釋劑和載體手冊], 第2版, Dorland Books, Caldwell, New Jersey [考德威爾, 新澤西州]中有所描述。 Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (for example, lactose, sucrose), silicon dioxide, talc, Mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers , 2nd ed., Dorland Books, Caldwell, New Jersey [Caldwell, NJ] described.
液體稀釋劑包括例如水、 N, N-二甲基烷醯胺（例如， N, N-二甲基甲醯胺）、檸檬烯、二甲基亞碸、 N-烷基吡咯啶酮（例如， N-甲基吡咯啶酮）、磷酸烷基酯（例如，磷酸三乙酯）、乙二醇、三甘醇、丙二醇、二丙二醇、聚丙二醇、碳酸丙烯酯、碳酸丁烯酯、石蠟（例如白礦物油、正鏈烷烴、異鏈烷烴）、烷基苯、烷基萘、甘油、三乙酸甘油酯、山梨糖醇、芳烴、脫芳構化脂族化合物、烷基苯、烷基萘、酮（諸如環己酮、2-庚酮、異佛爾酮和4-羥基-4-甲基-2-戊酮）、乙酸酯（諸如乙酸異戊酯、乙酸己酯、乙酸庚酯、乙酸辛酯、乙酸壬酯、乙酸十三烷基酯和乙酸異冰片酯）、其他酯（諸如烷基化乳酸酯、二元酯、苯甲酸烷基和芳基酯）γ-丁內酯以及可以是直鏈、支鏈、飽和或不飽和的醇，諸如甲醇、乙醇、正丙醇、異丙醇、正丁醇、異丁醇、正己醇、2-乙基己醇、正辛醇、癸醇、異癸醇、異十八烷醇、鯨蠟醇、月桂醇、十三烷醇、油醇、環己醇、四氫糠醇、雙丙酮醇、甲酚和苄醇。液體稀釋劑還包括飽和的和不飽和的脂肪酸（典型地為C 6-C 22）的甘油酯，諸如植物種子和果實油（例如，橄欖油、蓖麻油、亞麻籽油、芝麻油、玉米油（玉蜀黍油）、花生油、葵花籽油、葡萄籽油、紅花油、棉籽油、大豆油、油菜籽油、椰子油和棕櫚仁油)，動物源脂肪（例如，牛脂、豬脂、豬油、魚肝油、魚油），以及其混合物。液體稀釋劑還包括烷基化（例如甲基化、乙基化、丁基化）脂肪酸，其中脂肪酸可以藉由來自植物和動物來源的甘油酯的水解獲得，並且可藉由蒸餾純化。典型的液體稀釋劑在Marsden, Solvents Guide[溶劑指南], 第2版, Interscience, New York [紐約], 1950中進行描述。 Liquid diluents include, for example, water, N , N -dimethylalkanamides (e.g., N , N -dimethylformamide), limonene, dimethylsulfoxide, N -alkylpyrrolidones (e.g., N -methylpyrrolidone), alkyl phosphates (e.g. triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g. white mineral oil, n-paraffin, isoparaffin), alkylbenzene, alkylnaphthalene, glycerin, triacetin, sorbitol, aromatic hydrocarbon, dearomatized aliphatic compound, alkylbenzene, alkylnaphthalene, 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 lactates, dibasic esters, alkyl and aryl benzoates) gamma-butyrolactone and alcohols which may be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol , Decyl Alcohol, Isodecyl Alcohol, Isostearyl Alcohol, Cetyl Alcohol, Lauryl Alcohol, Tridecyl Alcohol, Oley Alcohol, Cyclohexanol, Tetrahydrofurfuryl Alcohol, Diacetone Alcohol, Cresol, and Benzyl Alcohol. Liquid diluents also include glycerides of saturated and unsaturated fatty acids (typically C6 - C22 ), such as vegetable seed and fruit oils (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil ( corn oil), peanut oil, sunflower oil, grapeseed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil, and palm kernel oil), fats of animal origin (e.g., tallow, lard, lard, cod liver oil , fish oil), and mixtures thereof. Liquid diluents also include alkylated (eg, methylated, ethylated, butylated) fatty acids, which fatty acids can be obtained by hydrolysis of glycerides from vegetable and animal sources and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide , 2nd ed., Interscience, New York, 1950.
本揭露之固體和液體組成物經常包括一種或多種表面活性劑。當添加到液體中時，表面活性劑（surfactant，也稱為「表面活性劑（surface-active agent）」）通常改變、最經常地降低液體的表面張力。根據表面活性劑分子中的親水和親脂基團的性質，表面活性劑可用作潤濕劑、分散劑、乳化劑或消泡劑。The solid and liquid compositions of the present disclosure often include one or more surfactants. When added to a liquid, surfactants (also known as "surface-active agents") generally alter, most often lower, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, surfactants can act as wetting agents, dispersants, emulsifiers or defoamers.
表面活性劑可以分類為非離子的、陰離子的或陽離子的。可用於本發明組成物的非離子表面活性劑包括但不限於：醇烷氧基化物，諸如基於天然醇和合成醇（其可以是支鏈或直鏈的）並且由醇和環氧乙烷、環氧丙烷、環氧丁烷或其混合物製備的醇烷氧基化物；胺乙氧基化物、鏈烷醇醯胺和乙氧基化鏈烷醇醯胺；烷氧基化甘油三酯，諸如乙氧基化的大豆油、蓖麻油和油菜籽油；烷基酚烷氧基化物，諸如辛基酚乙氧基化物、壬基酚乙氧基化物、二壬基酚乙氧基化物和十二烷基酚乙氧基化物（由苯酚和環氧乙烷、環氧丙烷、環氧丁烷或其混合物製備）；由環氧乙烷或環氧丙烷製備的嵌段聚合物和其中末端嵌段由環氧丙烷製備的反式嵌段聚合物；乙氧基化脂肪酸；乙氧基化脂肪酯和油；乙氧基化甲酯；乙氧基化三苯乙烯基酚（包括由環氧乙烷、環氧丙烷、環氧丁烷或其混合物製備的那些）；脂肪酸酯、甘油酯、羊毛脂基衍生物、多乙氧基化酯（諸如多乙氧基化脫水山梨糖醇脂肪酸酯、多乙氧基化山梨糖醇脂肪酸酯和多乙氧基化甘油脂肪酸酯）；其他脫水山梨糖醇衍生物諸如脫水山梨糖醇酯；聚合物表面活性劑，諸如無規共聚物、嵌段共聚物、醇酸peg（聚乙二醇）樹脂、接枝或梳型聚合物以及星型聚合物；聚乙二醇（peg）；聚乙二醇脂肪酸酯；矽酮基表面活性劑；和糖衍生物，諸如蔗糖酯、烷基多糖苷和烷基多糖。Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful in the compositions of the present invention include, but are not limited to: alcohol alkoxylates, such as those based on natural alcohols and synthetic alcohols (which may be branched or linear) and composed of alcohols and ethylene oxide, epoxy Alcohol alkoxylates prepared from propane, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated oxylated soybean oil, castor oil and rapeseed oil; alkylphenol alkoxylates such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecane phenol ethoxylates (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and in which the end blocks are composed of Trans-block polymers prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including , propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerides, lanolin-based derivatives, polyethoxylated esters (such as polyethoxylated sorbitan fatty acid esters , polyethoxylated sorbitan fatty acid esters and polyethoxylated glycerol fatty acid esters); other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, Block copolymers, alkyd PEG (polyethylene glycol) resins, graft or comb polymers, and star polymers; polyethylene glycol (PEG); polyethylene glycol fatty acid esters; silicone-based surfactants agents; and sugar derivatives, such as sucrose esters, alkyl polyglycosides, and alkyl polysaccharides.
有用的陰離子表面活性劑包括但不限於：烷基芳基磺酸及其鹽；羧化的醇或烷基酚乙氧基化物；二苯基磺酸酯衍生物；木質素和木質素衍生物，諸如木質素磺酸鹽；馬來酸或琥珀酸或它們的酸酐；烯烴磺酸酯；磷酸酯，諸如醇烷氧基化物的磷酸酯，烷基酚烷氧基化物的磷酸酯和苯乙烯基酚乙氧基化物的磷酸酯；蛋白質基表面活性劑；肌胺酸衍生物；苯乙烯基酚醚硫酸鹽；油和脂肪酸的硫酸鹽和磺酸鹽；乙氧基化烷基酚的硫酸鹽和磺酸鹽；醇的硫酸鹽；乙氧基化醇的硫酸鹽；胺和醯胺的磺酸鹽，諸如 N, N-烷基牛磺酸鹽；苯、異丙苯、甲苯、二甲苯以及十二烷基苯和十三烷基苯的磺酸鹽；縮聚萘的磺酸鹽；萘和烷基萘的磺酸鹽；石油級份的磺酸鹽；磺基琥珀醯胺酸鹽；以及磺基琥珀酸鹽和它們的衍生物，諸如二烷基磺基琥珀酸鹽。 Useful anionic surfactants include, but are not limited to: alkylarylsulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenylsulfonate derivatives; lignin and lignin derivatives , such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphoric esters, such as phosphates of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and styrene Phosphate esters of alkylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates of ethoxylated alkylphenols Salts and sulfonates; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N , N -alkyl taurates; benzene, cumene, toluene, di Toluene and sulfonates of dodecylbenzene and tridecylbenzene; sulfonates of polycondensed naphthalene; sulfonates of naphthalene and alkylnaphthalene; sulfonates of petroleum fractions; sulfosuccinamate and sulfosuccinates and their derivatives, such as dialkylsulfosuccinates.
有用的陽離子表面活性劑包括但不限於：醯胺和乙氧基化醯胺；胺諸如 N-烷基丙二胺、三伸丙基三胺和二伸丙基四胺，和乙氧基化胺、乙氧基化二胺以及丙氧基化胺（由胺和環氧乙烷、環氧丙烷、環氧丁烷或其混合物製備）；胺鹽諸如乙酸銨和二胺鹽；季銨鹽諸如季鹽、乙氧基化季鹽和二季鹽；以及胺氧化物，諸如烷基二甲基胺氧化物和雙-(2-羥乙基)-烷基胺氧化物。 Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; Amines, ethoxylated diamines and propoxylated amines (prepared from amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as ammonium acetate and diamine salts; quaternary ammonium salts Such as quaternary salts, ethoxylated quaternary salts, and diquaternary salts; and amine oxides, such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
還可用於本發明組成物的是非離子表面活性劑和陰離子表面活性劑的混合物、或非離子表面活性劑和陽離子表面活性劑的混合物。非離子表面活性劑、陰離子表面活性劑和陽離子表面活性劑以及它們的推薦用途揭露於多個已公佈的參考文獻中，包括由Manufacturing Confectioner出版公司的McCutcheon’s Division出版的 McCutcheon’s Emulsifiers and Detergents[McCutcheon的乳化劑和清潔劑], annual American and International Editions[美國和國際年度版]；Sisely和Wood, Encyclopedia of Surface Active Agents[表面活性劑百科全書], Chemical Publ.Co., Inc. [化學出版有限公司], 紐約, 1964；以及A. S. Davidson和B. Milwidsky, Synthetic Detergents[合成洗滌劑], 第七版, John Wiley and Sons [約翰威利父子公司], 紐約, 1987。 Also useful in the compositions of the present invention are mixtures of nonionic and anionic surfactants, or mixtures of nonionic and cationic surfactants. Nonionic, anionic, and cationic surfactants and their recommended uses are disclosed in various published references, including McCutcheon's Emulsifiers and Detergents [McCutcheon's Emulsifiers and Detergents ] published by McCutcheon's Division of Manufacturing Confectioner Publishing Company. Agents and Detergents], annual American and International Editions; Sisely and Wood, Encyclopedia of Surface Active Agents [Encyclopedia of Surface Active Agents], Chemical Publ.Co., Inc. [Chemical Publishing Co., Ltd.] , New York, 1964; and AS Davidson and B. Milwidsky, Synthetic Detergents , Seventh Edition, John Wiley and Sons, New York, 1987.
本揭露之組成物還可包含熟悉該項技術者已知為製劑輔助的製劑助劑和添加劑（其中一些也可被認為係起到固體稀釋劑、液體稀釋劑或表面活性劑作用）。此類製劑助劑和添加劑可控制：pH（緩衝劑）、加工過程中的起泡（消泡劑，諸如聚有機矽氧烷）、活性成分的沈降（懸浮劑）、黏度（觸變增稠劑）、容器內的微生物生長（抗微生物劑）、產品冷凍（防凍劑）、顏色（染料/顏料分散體）、洗脫（成膜劑或黏著劑）、蒸發（蒸發阻滯劑）以及其他製劑屬性。成膜劑包括例如聚乙酸乙烯酯、聚乙酸乙烯酯共聚物、聚乙烯吡咯啶酮-乙酸乙烯酯共聚物、聚乙烯醇、聚乙烯醇共聚物和蠟。製劑助劑和添加劑的實例包括以下中列出的那些：由Manufacturing Confectioner出版公司的McCutcheon’s Division出版的 McCutcheon’s Volume 2: Functional Materials[McCutcheon的第2卷：功能材料], annual International and North American editions [國際和北美年度版]；和PCT公佈WO 03/024222。 The compositions of the present disclosure may also contain formulation adjuvants and additives known to those skilled in the art as formulation aids (some of which may also be considered to act as solid diluents, liquid diluents or surfactants). Such formulation aids and additives control: pH (buffers), foaming during processing (defoamers, such as polyorganosiloxanes), settling of active ingredients (suspension agents), viscosity (thixotropic thickening agents), microbial growth in containers (antimicrobials), product freezing (antifreeze), color (dye/pigment dispersions), elution (film formers or adhesives), evaporation (evaporation retardants), and others formulation properties. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and additives include those listed in: McCutcheon's Volume 2: Functional Materials [McCutcheon's Volume 2: Functional Materials], annual International and North American editions [International and North American Annual Edition]; and PCT Publication WO 03/024222.
典型地藉由將活性成分溶於溶劑中或者藉由在液體或乾稀釋劑中研磨將式 1的化合物和任何其他活性成分摻入本發明組成物中。可藉由簡單地混合該等成分來製備包括可乳化的濃縮物的溶液。如果旨在用作可乳化的濃縮物的液體組成物的溶劑係與水不混溶的，典型地加入乳化劑以使含有活性成分的溶劑在用水稀釋時乳化。粒徑多達2,000 μm的活性成分漿料可以使用介質研磨機進行濕法研磨，以得到平均粒徑低於3 μm的顆粒。水性漿液可以製成成品懸浮液濃縮物（參見，例如，U.S. 3,060,084）或藉由噴霧乾燥進一步加工以形成水可分散的顆粒劑。乾製劑通常需要乾研磨過程，產生在2 μm至10 μm範圍內的平均粒徑。粉劑和粉末可以藉由共混並且通常藉由研磨（例如用錘磨機或流能磨）來製備。可以藉由將活性物質噴霧在預成形的顆粒劑載體上或者藉由附聚技術來製備顆粒劑和球劑。參見，Browning，「Agglomeration [附聚]」, Chemical Engineering[化學工程], 1967年12月4日, 第147-48頁； Perry’s Chemical Engineer’s Handbook[佩里化學工程師手冊], 第4版, McGraw-Hill [麥格勞希爾集團], 紐約, 1963, 第8-57頁及其後頁，以及WO 91/13546。球劑可以如U.S. 4,172,714中所述製備。水可分散的和水溶性的顆粒劑可如在U.S. 4,144,050、U.S. 3,920,442和DE 3,246,493中傳授的來製備。片劑可以如在U.S. 5,180,587、U.S. 5,232,701和U.S. 5,208,030中所傳授的來製備。膜可以如在GB 2,095,558和U.S. 3,299,566中所傳授的來製備。 The compound of Formula 1 and any other active ingredient are typically incorporated into the compositions of the invention by dissolving the active ingredient in a solvent or by triturating in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of the liquid composition intended to be used as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the solvent containing the active ingredient upon dilution with water. Active ingredient slurries with particle sizes up to 2,000 μm can be wet ground using a media mill to obtain particles with an average particle size below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, eg, US 3,060,084) or processed further by spray drying to form water-dispersible granules. Dry formulations typically require a dry milling process, yielding average particle sizes in the range of 2 μm to 10 μm. Dusts and powders can be prepared by blending and usually by grinding, for example with a hammer mill or a fluid energy mill. Granules and pellets can be prepared by spraying the active substance onto preformed granule carriers or by agglomeration techniques. See, Browning, "Agglomeration," Chemical Engineering , Dec. 4, 1967, pp. 147-48; Perry's Chemical Engineer's Handbook , 4th ed., McGraw- Hill [McGraw-Hill Group], New York, 1963, pp. 8-57 ff., 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 may be prepared as taught in US 5,180,587, US 5,232,701 and US 5,208,030. Membranes can be prepared as taught in GB 2,095,558 and US 3,299,566.
關於製劑領域的進一步資訊，參見T. S. Woods, Pesticide Chemistry and Bioscience, The Food–Environment Challenge[農藥化學與生物科學，食品與環境挑戰]中的「The Formulator’s Toolbox – Product Forms for Modern Agriculture [製劑工具箱 - 現代農業產品形式]」, T. Brooks和T. R. Roberts編輯, Proceedings of the 9th International Congress on Pesticide Chemistry [第九屆農藥化學國際會議論文集]，The Royal Society of Chemistry [皇家化學學會], Cambridge [劍橋], 1999, 第120-133頁。還可參見U.S.3,235,361，第6欄，第16行至第7欄，第19行和實例10-41；U.S 3,309,192，第5欄，第43行至第7欄，第62行和實例8、12、15、39、41、52、53、58、132、138-140、162-164、166、167和169-182；U.S.2,891,855，第3欄，第66行至第5欄，第17行和實例1-4；Klingman, Weed Control as a Science[雜草控制科學]，John Wiley and Sons, Inc.[約翰威利父子公司], 紐約, 1961, 第81–96頁；Hance等人, Weed Control Handbook[雜草控制手冊], 第8版, Blackwell Scientific Publications [布萊克威爾科學出版社], 牛津, 1989；和 Developments in formulation technology[製劑技術的發展], PJB Publications [PJB出版公司], 里士滿, UK, 2000。 For further information on the field of formulation, see "The Formulator's Toolbox – Product Forms for Modern Agriculture" in TS Woods, Pesticide Chemistry and Bioscience, The Food–Environment Challenge . Modern Agricultural Product Forms]”, edited by T. Brooks and TR Roberts, Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge ], 1999, pp. 120-133. See also US 3,235,361, column 6, lines 16 to 7, line 19 and examples 10-41; US 3,309,192, column 5, lines 43 to 7, line 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167, and 169-182; US 2,891,855, column 3, line 66 to column 5, line 17 Rows and Examples 1-4; Klingman, Weed Control as a Science , John Wiley and Sons, Inc., New York, 1961, pp. 81–96; Hance et al., Weed Control Handbook [Weed Control Handbook], 8th Edition, Blackwell Scientific Publications [Blackwell Science Press], Oxford, 1989; and Developments in formulation technology [Development of Formulation Technology], PJB Publications [PJB Publishing Company], Richmond, UK, 2000.
在以下實例中，所有制劑均以常規的方式製備。化合物編號係指索引表A至索引表F中的化合物。無需進一步詳盡說明，據信熟悉該項技術者使用前述說明可將本揭露利用至其最大程度。因此，以下實例應被解釋為僅是說明性的，並且不以任何方式限制本揭露。除非另外指明，否則百分比按重量計。In the following examples, all formulations were prepared in conventional manner. Compound numbers refer to compounds in Index Table A to Index Table F. Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present disclosure to its fullest extent. Accordingly, the following examples should be construed as merely illustrative, and not limiting of the present disclosure in any way. Percentages are by weight unless otherwise indicated.
實例A
實例B
實例C
實例D
實例E
實例F
實例G
實例H
實例I
實例J
實例K
實例L
本揭露之化合物表現出針對廣譜的無脊椎害蟲的活性。該等害蟲包括棲息在各種環境中的無脊椎動物，該等環境例如像植株的葉子、根、土壤、收穫的作物或其他食品、建築結構或動物皮膚（integument）。該等害蟲包括，例如，以葉子（包括葉、莖、花和果實）、種子、木材、紡織纖維或動物血液或組織為食並因此對例如生長中或儲存的農學作物、森林、溫室作物、觀賞植物、苗圃作物、儲存食品和纖維產品、或房屋或其他結構或它們的內容物造成傷害或損害，或對動物健康或公共健康有害的無脊椎動物。熟悉該項技術者將理解，並不是所有的化合物對所有害蟲的所有生長階段皆為同等有效的。The compounds of the present disclosure exhibit activity against a broad spectrum of invertebrate pests. Such pests include invertebrates that inhabit various environments such as leaves of plants, roots, soil, harvested crops or other food, building structures or animal integument. Such pests include, for example, feed on foliage (including foliage, stems, flowers and fruit), seeds, wood, textile fibers or animal blood or tissue and are therefore harmful to, for example, growing or stored agronomic crops, forestry, greenhouse crops, Invertebrates that cause injury or damage to ornamental plants, nursery crops, stored food and fiber products, or houses or other structures or their contents, or are detrimental to animal health or public health. Those skilled in the art will understand that not all compounds are equally effective against all growth stages of all pests.
因此，該等本發明之化合物和組成物在農學上可用於保護大田作物免受植食性無脊椎害蟲的侵害，並且在非農學上也可用於保護其他園藝作物和植株免受植食性無脊椎害蟲的侵害。該效用包括保護含有藉由遺傳工程（即轉基因）引入或藉由誘變改性的遺傳物質的作物和其他植株（即，農學和非農學的），以提供有利性狀。此類性狀的實例包括對除草劑耐受、對植食性害蟲（例如，昆蟲、蟎蟲、蚜蟲、蜘蛛、線蟲、蝸牛、植物病原真菌、細菌和病毒）具有抗性、植株生長得到改善、對不利生長條件（諸如高溫或低溫、低土壤水分或高土壤水分、和高鹽度）的耐受性增加、開花或結果增加、收穫產量更大、成熟更快、收穫產品的品質和/或營養價值更高、或收穫產品的儲存或加工特性得到改善。轉基因植物可被改性以表現多種性狀。含有由遺傳工程或誘變提供的性狀的植物的實例包括表現蘇力菌殺昆蟲毒素的玉米、棉花、大豆和馬鈴薯品種，諸如YIELD GARD ®、KNOCKOUT ®、STARLINK ®、BOLLGARD ®、NuCOTN ®和NEWLEAF ®、INVICTA RR2 PRO TM，和耐除草劑的玉米、棉花、大豆和菜籽品種，諸如ROUNDUP READY ®、LIBERTY LINK ®、IMI ®、STS ®和CLEARFIELD ®，以及表現 N-乙醯轉移酶（GAT）以提供對草甘膦除草劑的抗性的作物、或含有提供對抑制乙醯乳酸合成酶（ALS）的除草劑的抗性的HRA基因的作物。本發明之化合物和組成物可表現出藉由遺傳工程引入或藉由誘變改性的性狀的增強效應，從而增強性狀的表型表現或有效性，或增加本發明化合物和組成物的無脊椎害蟲防治有效性。特別地，本發明之化合物和組成物可表現出蛋白質或對無脊椎害蟲有毒的其他天然產品的表型表現的增強效應，以提供對該等害蟲的大於加性的防治。 Accordingly, the compounds and compositions of the present invention are useful agronomically for the protection of field crops from phytophagous invertebrate pests and non-agronomically for the protection of other horticultural crops and plants from phytophagous invertebrate pests infringement. This utility includes the protection of crops and other plants (ie, agronomic and non-agronomic) containing genetic material introduced by genetic engineering (ie, transgenes) or modified by mutagenesis to provide beneficial traits. Examples of such traits include herbicide tolerance, resistance to herbivorous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, phytopathogenic fungi, bacteria and viruses), improved plant growth, adverse Increased tolerance of growing conditions (such as high or low temperature, low or high soil moisture, and high salinity), increased flowering or fruiting, greater harvest yield, faster ripening, quality and/or nutritional value of harvested product Taller, or improved storage or processing characteristics of the harvested product. Transgenic plants can be modified to exhibit a variety of traits. Examples of plants containing traits conferred by genetic engineering or mutagenesis include maize, cotton, soybean, and potato varieties expressing Thulein insecticidal toxins, such as YIELD GARD ® , KNOCKOUT ® , STARLINK ® , BOLLGARD ® , NuCOTN ® and NEWLEAF ® , INVICTA RR2 PRO TM , and herbicide-tolerant corn, cotton, soybean, and rapeseed varieties such as ROUNDUP READY ® , LIBERTY LINK ® , IMI ® , STS ® and CLEARFIELD ® , and N -acetyltransferase (GAT ) to provide crops resistant to glyphosate herbicides, or crops containing HRA genes that provide resistance to herbicides that inhibit acetyl lactate synthase (ALS). The compounds and compositions of the invention may exhibit enhancement of traits introduced by genetic engineering or modified by mutagenesis, thereby enhancing the phenotypic expression or effectiveness of the traits, or increasing the invertebrate activity of the compounds and compositions of the invention. Effectiveness of pest control. In particular, the compounds and compositions of the invention may exhibit enhancing effects on the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide more than additive control of such pests.
本揭露之組成物還可視需要包含植物營養素，例如，肥料組成物，該肥料組成物包含至少一種選自氮、磷、鉀、硫、鈣、鎂、鐵、銅、硼、錳、鋅和鉬的植物營養素。值得注意的是包含至少一種肥料組成物的組成物，該至少一種肥料組成物包含至少一種選自氮、磷、鉀、硫、鈣和鎂的植物營養素。進一步包含至少一種植物營養素的本揭露組成物可以呈液體或固體的形式。值得注意的是呈顆粒劑、棒或片劑形式的固體製劑。可藉由將本揭露之化合物或組成物與肥料組成物以及製劑成分混合，並且然後藉由諸如造粒或擠壓之方法製備製劑來製備包含肥料組成物的固體製劑。替代性地，可藉由將本揭露之化合物或組成物在揮發性溶劑中的溶液或懸浮液噴霧在先前製備的呈尺寸穩定的混合物（例如，顆粒劑、棒或片劑）形式的肥料組成物上，並且然後將溶劑蒸發來製備固體製劑。The composition of the present disclosure may also include plant nutrients as desired, for example, a fertilizer composition comprising at least one compound selected from the group consisting of nitrogen, phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc and molybdenum. of phytonutrients. Of note are compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulphur, calcium and magnesium. Compositions of the present disclosure further comprising at least one phytonutrient may be in liquid or solid form. Of note are solid formulations in the form of granules, sticks or tablets. A solid formulation comprising a fertilizer composition can be prepared by mixing a compound or composition of the present disclosure with a fertilizer composition and formulation ingredients, and then preparing a formulation by a method such as granulation or extrusion. Alternatively, the fertilizer may be formed by spraying a solution or suspension of a compound or composition of the present disclosure in a volatile solvent onto a previously prepared fertilizer in the form of a dimensionally stable mixture (e.g., granules, sticks or tablets). material, and then the solvent was evaporated to prepare a solid formulation.
非農學用途係指在作物植株大田以外的區域中的無脊椎害蟲防治。本發明之化合物和組成物的非農學用途包括在儲存的穀物、豆類和其他食品以及紡織品諸如衣服和地毯中的無脊椎害蟲防治。本發明之化合物和組成物的非農學用途還包括在觀賞植物、森林、庭院、路邊和鐵路用地以及草皮諸如草坪、高爾夫球場和牧場中的無脊椎害蟲防治。本發明之化合物和組成物的非農學用途還包括在房屋和可能被人類和/或伴侶動物、農場動物、牧場動物、動物園動物或其他動物佔據的其他建築物中的無脊椎害蟲防治。本發明之化合物和組成物的非農學用途還包括可能損害建築物中使用的木材或其他結構材料的害蟲諸如白蟻的防治。Non-agronomic use refers to invertebrate pest control in areas other than fields of crop plants. Non-agronomic uses of the compounds and compositions of the invention include invertebrate pest control in stored grains, legumes and other food products, and textiles such as clothing and carpets. Non-agronomic uses of the compounds and compositions of this invention also include invertebrate pest control in ornamentals, forests, gardens, roadsides and railroad fields, and turf such as lawns, golf courses and pastures. Non-agronomic uses of the compounds and compositions of the present invention also include invertebrate pest control in houses and other structures that may be occupied by humans and/or companion, farm, ranch, zoo or other animals. Non-agronomic uses of the compounds and compositions of the invention also include the control of pests, such as termites, which may damage wood or other structural materials used in buildings.
本發明之化合物和組成物的非農學用途還包括藉由防治寄生的或傳播感染性疾病的無脊椎害蟲來保護人類和動物健康。對動物寄生蟲的防治包括防治寄生在宿主動物身體表面（例如，肩部、腋窩、腹部、大腿內側）的外部寄生蟲和寄生在宿主動物身體內部（例如，胃、腸、肺、靜脈、皮下、淋巴組織）的內部寄生蟲。外部寄生的或傳播疾病的害蟲包括，例如，恙蟎（chigger）、蜱蟲（tick）、虱、蚊子、蠅、蟎蟲和跳蚤。內部寄生蟲包括心絲蟲、鉤蟲和蠕蟲。本揭露之化合物和組成物適用於全身性和/或非全身性防治動物上寄生蟲的侵害或感染。本揭露之化合物和組成物特別適用於對抗外部寄生的或傳播疾病的害蟲。本揭露之化合物和組成物適用於對抗侵害以下動物的寄生蟲：農業工作動物，諸如牛、羊、山羊、馬、豬、驢、駱駝、水牛、兔子、母雞、火雞、鴨子、鵝和蜜蜂；寵物動物和家養動物，諸如狗、貓、寵物鳥和水族館魚類；以及所謂的實驗動物，諸如倉鼠、豚鼠、大鼠和小鼠。藉由對抗該等寄生蟲，降低了死亡率和性能下降（在肉、奶、羊毛、毛皮、蛋、蜂蜜等方面），因此施加包含本揭露之化合物的組成物允許更經濟且簡單的動物飼養。Non-agronomic uses of the compounds and compositions of the invention also include the protection of human and animal health by controlling parasitic or infectious disease-transmitting invertebrate pests. Control of animal parasites includes control of ectoparasites that live on the host animal's body surface (eg, shoulders, armpits, abdomen, inner thighs) and internal host animals (eg, stomach, intestines, lungs, veins, subcutaneous , lymphoid tissue) internal parasites. Externally parasitic or disease-transmitting pests include, for example, chiggers, ticks, lice, mosquitoes, flies, mites, and fleas. Internal parasites include heartworms, hookworms, and worms. The disclosed compounds and compositions are suitable for systemic and/or non-systemic control of parasitic infestation or infection in animals. The compounds and compositions of the present disclosure are particularly useful in combating ectoparasitic or disease-transmitting pests. The compounds and compositions of the present disclosure are useful in combating parasites that attack agricultural working animals such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, hens, turkeys, ducks, geese and Bees; pet and domestic animals such as dogs, cats, pet birds and aquarium fish; and so-called laboratory animals such as hamsters, guinea pigs, rats and mice. By combating these parasites, mortality and performance degradation (in meat, milk, wool, fur, eggs, honey, etc.) is reduced, thus applying compositions comprising compounds of the present disclosure allows for more economical and simple animal husbandry .
農學或非農學無脊椎害蟲的實例包括鱗翅目（Lepidoptera）的卵、幼蟲和成蟲，諸如夜蛾科（Noctuidae）的黏蟲（armyworm）、切根蟲（cutworm）、尺蠖（looper）和實夜蛾亞科（heliothine）（例如，大螟（ Sesamia inferensWalker）、玉米螟（ Sesamia nonagrioidesLefebvre）、南方黏蟲（ Spodoptera eridaniaCramer）、秋黏蟲（ Spodoptera frugiperdaJ. E. Smith）、甜菜夜蛾（ Spodoptera exiguaHübner）、棉葉蟲 Spodoptera littoralisBoisduval）、黃帶黏蟲（ Spodoptera ornithogalliGuenée）、小地老虎（ Agrotis ipsilonHufnagel）、藜豆夜蛾（ Anticarsia gemmatalisHübner）、綠果夜蛾（ Lithophane antennataWalker）、甘藍夜蛾（ Barathra brassicaeLinnaeus）、大豆夜蛾（ Pseudoplusia includensWalker）、粉紋夜蛾（ Trichoplusia niHübner）、煙青蟲（ Heliothis virescensFabricius））；來自螟蛾科（Pyralidae）的螟蟲（borer）、鞘蛾（casebearer）、結網蟲（webworm）、毬果蟲（coneworm）、甘藍蟲（cabbageworm）和雕葉蟲（skeletonizer）（例如，歐洲玉米螟（ Ostrinia nubilalisHübner）、臍橙螟（ Amyelois transitellaWalker）、玉米根結網蟲（ Crambus caliginosellusClemens）、草地螟（螟蛾科：草螟亞科（ Crambinae）），諸如稻切葉野螟（ Herpetogramma licarsisalis Walker）、甘蔗二點螟（ Chilo infuscatellus Snellen）、番茄小鑽蛀蟲（ Neoleucinodes elegantalisGuenée）、稻縱卷葉螟（ Cnaphalocrocis medinalis）、葡萄卷葉蟲（ Desmia funeralisHübner）、甜瓜野螟（ Diaphania nitidalisStoll）、甘藍芯蠐螬（ Helluala hydralisGuenée）、三化螟（ Scirpophaga incertulasWalker）、早期嫩梢蛀蟲（ Scirpophaga infuscatellusSnellen）、白二化螟（ Scirpophaga innotataWalker）、頂部嫩梢蛀蟲（ Scirpophaga nivellaFabricius）、黑頭稻螟（ Chilo polychrysusMeyrick）、二化螟（ Chilo suppressalisWalker）、大菜螟（ Crocidolomia binotalisEnglish）；卷蛾科（Tortricidae）的卷葉蟲（leafroller）、蚜蟲（budworm）、種子蠕蟲（seed worm）和果實蠕蟲（fruit worm）（例如，蘋果蠹蛾（ Cydia pomonellaLinnaeus）、葡萄漿果蛾（ Endopiza viteanaClemens）、梨小食心蟲（ Grapholita molestaBusck）、蘋果異形小卷蛾（ Cryptophlebia leucotretaMeyrick）、柑橘天牛（ Ecdytolopha aurantianaLima）、紅帶卷蛾（ Argyrotaenia velutinanaWalker）、薔薇斜條卷葉蛾（ Choristoneura rosaceanaHarris）、蘋果淺褐卷葉蛾（ Epiphyas postvittanaWalker）、女貞細卷蛾（ Eupoecilia ambiguellaHübner）、蘋果頂芽卷葉蛾（ Pandemis pyrusanaKearfott）、雜食卷葉蛾（ Platynota stultanaWalsingham）、葡萄褐卷蛾（ Pandemis cerasanaHübner）、蘋果褐卷蛾（ Pandemis heparanaDenis & Schiffermüller））；和許多其他經濟上重要的鱗翅目（例如，小菜蛾（ Plutella xylostellaLinnaeus）、棉紅鈴蟲（ Pectinophora gossypiella Saunders）、舞毒蛾（ Lymantria disparLinnaeus）、桃小食心蟲（ Carposina niponensisWalsingham）、桃條麥蛾（ Anarsia lineatellaZeller）、馬鈴薯塊莖蛾（ Phthorimaea operculellaZeller）、（斑幕潛葉蛾（ Lithocolletis blancardellaFabricius）、蘋果金紋細蛾（ Lithocolletis ringoniellaMatsumura）、稻縱卷葉螟（ Lerodea eufalaEdwards）、旋紋潛葉蛾（ Leucoptera scitellaZeller））；蜚蠊目（Blattodea）的卵、若蟲和成蟲，包括來自姬蜚蠊科（Blattellidae）和蜚蠊科（Blattidae）的蟑螂（例如，東方蟑螂（ Blatta orientalisLinnaeus）、亞洲蟑螂（ Blatella asahinaiMizukubo）、德國蟑螂（ Blattella germanicaLinnaeus）、棕帶蟑螂（ Supella longipalpaFabricius）、美洲蟑螂（ Periplaneta americanaLinnaeus）、褐色蟑螂（ Periplaneta brunneaBurmeister）、馬德拉蟑螂（Madeira cockroach）（ Leucophaea maderaeFabricius）、黑胸蟑螂（ Periplaneta fuliginosaService）、澳洲蟑螂（ Periplaneta australasiaeFabr.）、龍蝦蟑螂（ Nauphoeta cinereaOlivier）和光滑蟑螂（ Symploce pallensStephens））；鞘翅目（Coleoptera）的卵、取食葉、取食果實、取食根、取食種子和取食囊泡組織的幼蟲和成蟲，包括來自長角象蟲科（Anthribidae）、豆象科（Bruchidae）和象蟲科 （Curculionidae）的象鼻蟲（weevil）（例如，棉籽象鼻蟲（ Anthonomus grandisBoheman）、稻水象甲（ Lissorhoptrus oryzophilusKuschel）、穀象（ Sitophilus granariusLinnaeus）、米象（ Sitophilus oryzaeLinnaeus）、早熟禾象鼻蟲（ Listronotus maculicollisDietz）、早熟禾穀象（ Sphenophorus parvulusGyllenhal）、獵食穀象（ Sphenophorus venatus vestitus）、丹佛穀象（ Sphenophorus cicatristriatusFahraeus））；葉甲科（Chrysomelidae）的跳甲（flea beetle）、黃守瓜（cucumber beetle）、根蟲（rootworm）、葉甲（leaf beetle）、馬鈴薯甲蟲（potato beetle）和潛葉蟲（leafminer）（例如，科羅拉多馬鈴薯甲蟲（ Leptinotarsa decemlineataSay）、西方玉米根蟲（ Diabrotica virgifera virgiferaLeConte））；來自金龜子科（Scarabaeidae）的金龜子和其他甲蟲（例如，日本麗金龜（ Popillia japonicaNewman）、東方麗金龜（ Anomala orientalisWaterhouse， Exomala orientalis(Waterhouse) Baraud）、北方獨角仙（ Cyclocephala borealisArrow）、南方獨角仙（ Cyclocephala immaculataOlivier或 C. luridaBland）、蜣螂（dung beetle）和蠐螬（white grub）（蜉金龜屬（ Aphodius）物種）、黑色草坪金龜（ Ataenius spretulusHaldeman）、綠色六月金龜（ Cotinis nitidaLinnaeus）、亞洲花園金龜（ Maladera castaneaArrow）、五月/六月金龜（鰓角金龜屬（ Phyllophaga）物種）和歐洲金龜子（ Rhizotrogus majalisRazoumowsky））；來自皮蠹科（Dermestidae）的紅緣皮蠹（carpet beetle）；來自叩甲科（Elateridae）的金針蟲（wireworm）；來自棘脛小蠹科（Scolytidae）的小蠹（bark beetle）和來自擬步甲科（Tenebrionidae）的麵粉甲蟲（flour beetle）。 Examples of agronomic or non-agronomic invertebrate pests include eggs, larvae, and adults of the order Lepidoptera, such as armyworms, cutworms, loopers, and seedworms of the family Noctuidae. Heliothine (e.g. Sesamia inferens Walker, Sesamia nonagrioides Lefebvre, Spodoptera eridania Cramer, Spodoptera frugiperda J. E. Smith, Spodoptera exigua Hübner), Spodoptera littoralis Boisduval), Spodoptera ornithogalli Guenée, Agrotis ipsilon Hufnagel, Anticarsia gemmatalis Hübner, Lithophane antennata Walker, Cabbage moth ( Barathra brassicae Linnaeus), soybean moth ( Pseudoplusia includesens Walker), trichoplusia ni Hübner, tobacco budworm ( Heliothis virescens Fabricius); borer from the family Pyralidae , casebearer, webworm, coneworm, cabbageworm, and skeletonizer (e.g., Ostrinia nubilalis Hübner, Amyelois transitella Walker ), corn root knot worm ( Crambus caliginosellus Clemens ), meadow borer (Boreridae: Crambinae ), such as rice leaf-cutting borer ( Herpetogramma licarsisalis Walker ), sugarcane two point borer ( Chilo infuscatellus Snellen ), Tomato borer ( Neoleucinodes elegantis Guenée), rice leaf roller ( Cnaphalocrocis medinalis ), grape leaf roller ( Desmia funeralis Hübner), melon borer ( Diaphania nitidalis Stoll), cabbage core grub ( Helluala hydralis Guenée), rice stem borer ( Scirpophaga incertulas Walker), early shoot borer ( Scirpophaga infuscatellus Snellen), white Chilophaga innotata Walker, Scirpophaga nivella Fabricius, Chilo polychrysus Meyrick, Chilo suppressalis Walker, Crocidolomia binotalis English; Tortricidae ), aphids (budworm), seed worms and fruit worms (e.g. Cydia pomonella Linnaeus, grape berry moth ( Endopiza viteana Clemens), Pear borer moth ( Grapholita molesta Busck), apple borer moth ( Cryptophlebia leucotreta Meyrick), citrus beetle ( Ecdytolopha aurantiana Lima), red banded moth ( Argyrotaenia velutinana Walker), rose oblique leaf tortrix ( Choristoneura rosaceana Harris) , Epiphyas postvittana Walker, Eupoecilia ambiguella Hübner, Pandemis pyrusana Kearfott, Platynota stultana Walsingham, Grape Brown ( Pandemis cerasana Hübner), apple brown bollworm ( Pandemis heparana Denis &Schiffermüller)); and many other economically important Lepidoptera (e.g. diamondback moth ( Plutella xylostella Linnaeus), cotton pink bollworm ( Pectinophora gos sypiella Saunders ), Lymantria dispar Linnaeus, Carposina niponensis Walsingham, Anarsia lineatella Zeller, Phthorimaea operculella Zeller, Lithocolletis blancardella Fabricius ), apple golden leaf miner ( Lithocolletis ringoniella Matsumura), rice leaf roller ( Lerodea eufala Edwards), spin leafminer ( Leucoptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea, including those from Cockroaches of the families Blattellidae and Blattidae (e.g., Oriental cockroach ( Blatta orientalis Linnaeus), Asian cockroach ( Blatella asahinai Mizukubo), German cockroach ( Blattella germanica Linnaeus), brown-banded cockroach ( Supella longipalpa Fabricius ), American cockroach ( Periplaneta americana Linnaeus), brown cockroach ( Periplaneta brunnea Burmeister), Madeira cockroach ( Leucophaea maderae Fabricius), black-breasted cockroach ( Periplaneta fuliginosa Service), Australian cockroach ( Periplaneta australasiae Fabr.), Lobster cockroaches ( Nauphoeta cinerea Olivier) and smooth cockroaches ( Symploce pallens Stephens)); egg-feeding, leaf-feeding, fruit-feeding, root-feeding, seed-feeding, and vesicle-feeding larvae and adults of the order Coleoptera , including weevils from the families Anthribidae, Bruchidae, and Curculionidae (e.g., Anthonomus grandis Boheman, rice water weevil ( Lissorhoptrus oryzophilus Kuschel ), Sitophilus granarius Linnaeus, Sitophilus oryzae Linnaeus, Listronotus maculicollis Dietz, Sphenophorus parvulus Gyllenhal, Sphenophorus venatus vestitus , Denver Grain elephant ( Sphenophorus cicatristriatus Fahraeus); flea beetle, cucumber beetle, rootworm, leaf beetle, potato beetle and latent Leafminers (e.g., Colorado potato beetle ( Leptinotarsa decemlineata Say), western corn rootworm ( Diabrotica virgifera virgifera LeConte)); scarabs and other beetles from the family Scarabaeidae (e.g., Popillia japonica Newman ), Oriental beetle ( Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northern unicorn ( Cyclocephala borealis Arrow), southern unicorn ( Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and White grub ( Aphodius species), black lawn beetle ( Ataenius spretulus Haldeman), green June beetle ( Cotinis nitida Linnaeus), Asian garden beetle ( Maladera castanea Arrow), May/June beetle ( species of the genus Phyllophaga ) and the European scarab ( Rhizotrogus majalis Razoumowsky); the carpet beetle from the family Dermestidae; the wireworm from the family Elateridae; From the family Scolytidae ) and the flour beetle from the family Tenebrionidae.
另外，農學和非農學害蟲包括：革翅目（Dermaptera）的卵、成蟲和幼蟲，包括來自蠼螋科（Forficulidae）的蠼螋（earwig）（例如，歐洲蠼螋（ Forficula auriculariaLinnaeus）、黑蠼螋（ Chelisoches morioFabricius））；半翅目（Hemiptera）的卵、幼蟲、成蟲和若蟲，諸如來自盲蝽科（Miridae）的盲蝽（plant bug）、來自蟬科（Cicadidae）的蟬（cicada）、來自大葉蟬科（Cicadellidae）的葉蟬（leafhopper）（例如，小綠葉蟬屬（ Empoasca）物種）、來自臭蟲科（Cimicidae）的臭蟲（bed bug）（例如，溫帶臭蟲（ Cimex lectulariusLinnaeus））、來自蠟蟬科（Fulgoridae）和飛虱科（Delphacidae）的飛虱（planthopper）、來自角蟬科（Membracidae）的角蟬（treehopper）、來自扁木虱科（Liviidae）、木虱科（Psyllidae）和個木虱科（Triozidae）的木虱（psyllid）、來自粉虱科（Aleyrodidae）的粉虱（whiteflies）、來自蚜科（Aphididae）的蚜蟲、來自根瘤蚜科（Phylloxeridae）的根瘤蚜（phylloxera）、來自粉蚧科（Pseudococcidae）的粉蚧（mealybug）、來自蚧科（Coccidae）、盾蚧科（Diaspididae）和綿蚧科（Margarodidae）的介殼蟲（scale）、來自網蝽科（Tingidae）的網蝽（lace bug）、來自蝽科（Pentatomidae）的蝽象（stink bug）、來自長蝽科（Lygaeidae）的長蝽（chinch bug）（例如，毛長蝽（ Blissus leucopterus hirtusMontandon）和南部長蝽（ Blissus insularisBarber））和其他來自長蝽科的籽長蝽（seed bug）、來自沫蟬科（Cercopidae）的沫蟬（spittlebug）、來自緣蝽科（Coreidae）的緣蝽（squash bug）以及來自紅蝽科（Pyrrhocoridae）的紅蝽（red bug）和棉紅蝽（cotton stainer）。 Additionally, agronomic and non-agronomic pests include: eggs, adults and larvae of the order Dermaptera, including earwigs from the family Forficulidae (eg, Forficula auricularia Linnaeus, black earwig Fly ( Chelisoches morio Fabricius); eggs, larvae, adults, and nymphs of the order Hemiptera, such as plant bugs from the family Miridae, cicadas from the family Cicadidae , leafhoppers from the family Cicadellidae (e.g., Empoasca species), bed bugs from the family Cimicidae (e.g., Cimex lectularius Linnaeus) , Planthoppers from Fulgoridae and Delphacidae, treehoppers from Membracidae, Liviidae, Psyllidae ) and psyllids from the family Triozidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae ( phylloxera), mealybugs from the family Pseudococcidae, scales from the families Coccidae, Diaspididae and Margarodidae, scales from the family Tingidae ), stink bugs from the family Pentatomidae, chinch bugs from the family Lygaeidae (for example, Blissus leucopterus hirtus Montandon and Southern longbug ( Blissus insulatingis Barber) and other seed bugs from the family Cyridae, spittlebug from Cercopidae, squash from Coreidae bug) and the red bug and cotton stainer from the family Pyrrhocoridae ).
農學和非農學害蟲還包括：蜱蟎目（Acari）（蟎蟲）的卵、幼蟲、若蟲和成蟲，諸如葉蟎科（Tetranychidae）的葉蟎（spider mite）和紅蟎（red mite）（例如，歐洲紅蟎（ Panonychus ulmiKoch）、二斑葉蟎（ Tetranychus urticaeKoch）、邁葉蟎（ Tetranychus mcdanieliMcGregor））；細須蟎科（Tenuipalpidae）的短須蟎（flat mite）（例如，桔短須蟎（ Brevipalpus lewisiMcGregor））；癭蟎科（Eriophyidae）的鏽蟎（rust mite）和芽蟎（bud mite）以及其他取食葉的蟎蟲和在人類和動物健康方面重要的蟎蟲，即表皮蟎科（Epidermoptidae）的塵蟎、蠕形蟎科（Demodicidae）的毛囊蟎、食甜蟎科（Glycyphagidae）的穀蟎；硬蜱科（Ixodidae）的蜱蟲，通常稱為硬蜱（例如，鹿蜱（ Ixodes scapularisSay）、澳大利亞麻痹蜱（ Ixodes holocyclusNeumann）、美洲犬蜱（ Dermacentor variabilisSay）、孤星蜱（ Amblyomma americanumLinnaeus））和軟蜱科（Argasidae）的蜱蟲，通常稱為軟蜱（例如，回歸熱蜱（ Ornithodoros turicata）、常見雞蜱（ Argas radiatus））；癢蟎科（Psoroptidae）、蒲蟎科（Pyemotidae）和疥蟎科（Sarcoptidae）的疥蟎（scab mite）和癢蟎（itch mite）；直翅目（Orthoptera）的卵、成蟲和幼蟲，包括蚱蜢、蝗蟲和蟋蟀（例如，遷徙蚱蜢（migratory grasshoppers）（例如，血黑蝗（ Melanoplus sanguinipesFabricius）、殊種蝗（ M. differentialisThomas）、美洲蚱蜢（American grasshoppers）（例如美洲沙漠蝗（ Schistocerca americanaDrury））、沙漠蝗（ Schistocerca gregariaForskal）、飛蝗（ Locusta migratoriaLinnaeus）、灌木蝗（bush locust）（腺蝗屬（ Zonocerus）物種）、家蟋蟀（ Acheta domesticusLinnaeus）、螻蛄（mole crickets）（例如，黃褐色螻蛄（ Scapteriscus vicinusScudder）和南美螻蛄（ Scapteriscus borelliiGiglio-Tos））；雙翅目（Diptera）的卵、成蟲和幼蟲，包括潛葉蟲（例如，斑潛蠅屬（ Liriomyza）物種，諸如蔬菜斑潛蠅（ Liriomyza sativaeBlanchard））、蠓、果蠅（實蠅科（Tephritidae））、麥稈蠅（例如，瑞典麥稈蠅（ Oscinella fritLinnaeus））、土壤蛆（soil maggots）、家蠅（例如，家蠅（ Musca domesticaLinnaeus））、小家蠅（例如，夏廁蠅（ Fannia canicularisLinnaeus）、小舍蠅（ F. femoralisStein））、廄螯蠅（stable flies）（例如，廄螯蠅（ Stomoxys calcitransLinnaeus））、秋家蠅（face flies）、角蠅（horn flies）、麗蠅（blow flies）（例如，金蠅屬（ Chrysomya）物種、伏蠅屬（ Phormia）物種）以及其他蠅類（muscoid fly）害蟲、馬蠅（horse flies）（例如，虻屬（ Tabanus）物種）、膚蠅（bot flies）（例如，胃蠅屬（ Gastrophilus）物種、狂蠅屬（ Oestrus）物種、紋皮蠅（cattle grubs）（例如，牛皮蠅屬（ Hypoderma）物種）、鹿虻（deer flies）（例如，斑虻屬（ Chrysops）物種）、羊蜱蠅（keds）（例如，綿羊虱蠅（ Melophagus ovinusLinnaeus））以及其他短角亞目（Brachycera）、蚊子（例如，伊蚊屬（ Aedes）物種、按蚊屬（ Anopheles）物種、庫蚊屬（ Culex）物種）、蚋（black flies）（例如，原蚋屬（ Prosimulium）物種、蚋屬（ Simulium）物種）、叮咬蠓（biting midges）、沙蠅（sand flies）、眼菌蚊（sciarids）和其他長角亞目（Nematocera）；纓翅目（Thysanoptera）的卵、成蟲、和幼蟲，包括洋蔥薊馬（ Thrips tabaciLindeman）、花薊馬（花薊馬屬（ Frankliniella）物種）以及其他取食葉子的薊馬；膜翅目（Hymenoptera）的昆蟲害蟲，包括蟻科（Formicidae）的螞蟻，包括佛羅里達木蟻（ Camponotus floridanusBuckley）、紅木蟻（ Camponotus ferrugineusFabricius）、黑木蟻（ Camponotus pennsylvanicusDe Geer）、白足蟻（ Technomyrmex albipesfr. Smith）、大頭蟻（大頭蟻屬（ Pheidole）物種）、幽靈蟻（ Tapinoma melanocephalumFabricius）；法老蟻（ Monomorium pharaonisLinnaeus）、小火蟻（ Wasmannia auropunctataRoger）、火蟻（ Solenopsis geminataFabricius）、紅火蟻（ Solenopsis invictaBuren）、阿根廷蟻（， Iridomyrmex humilisMayr）、瘋蟻（ Paratrechina longicornisLatreille）、鋪道蟻（ Tetramorium caespitumLinnaeus）、玉米田蟻（ Lasius alienusFörster）和香家蟻（ Tapinoma sessileSay）。其他膜翅目（Hymenoptera），包括蜂（包括木蜂（carpenter bees））、大黃蜂（hornets）、小黃蜂（yellow jackets）、胡蜂（wasps）和葉蜂（sawflies）（新松葉蜂屬（ Neodiprion）物種；莖蜂屬（ Cephus）物種）；等翅目（Isoptera）的昆蟲害蟲，包括白蟻科（Termitidae）（例如，大白蟻屬（ Macrotermes）物種、土白蟻（ Odontotermes obesusRambur））、木白蟻科（Kalotermitidae）（例如，堆砂白蟻屬（ Cryptotermes）物種）、以及鼻白蟻科（Rhinotermitidae）（例如，散白蟻屬（ Reticulitermes）物種、乳白蟻屬（ Coptotermes）物種、鼻異白蟻（ Heterotermes tenuisHagen））的白蟻，東部地下白蟻（ Reticulitermes flavipes Kollar）、西部地下白蟻（ Reticulitermes hesperusBank）、台灣乳白蟻（ Coptotermes formosanusShiraki）、西印度乾木白蟻（ Incisitermesimmigrans Snyder）、粉白蟻（ Cryptotermes brevisWalker）、乾木白蟻（ Incisitermes snyderiLight）、東南部地下白蟻（ Reticulitermes virginicusBanks）、西部乾木白蟻（ Incisitermes minorHagen）、樹棲白蟻（arboreal termites）諸如象白蟻屬（ Nasutitermes）物種，以及其他具有經濟重要性的白蟻；纓尾目（Thysanura）的昆蟲害蟲，諸如蠹蟲（ Lepisma saccharinaLinnaeus）和家衣魚（ Thermobia domesticaPackard）；食毛目（Mallophaga）的昆蟲害蟲，包括頭蝨（ Pediculus humanus capitisDe Geer）、體虱（ Pediculus humanusLinnaeus）、雞體虱（ Menacanthus stramineusNitszch）、狗齧毛虱（ Trichodectes canisDe Geer）、絨毛虱（ Goniocotes gallinae De Geer）、羊體虱（ Bovicolaovis Schrank）、短鼻牛虱（ Haematopinus eurysternusNitzsch）、長鼻牛虱（ Linognathus vituliLinnaeus）以及其他攻擊人和動物的吸吮和嚼咬型寄生虱；蚤目（Siphonoptera）的昆蟲害蟲，包括東方鼠蚤（ Xenopsylla cheopisRothschild）、貓蚤（ Ctenocephalides felisBouche）、犬蚤（ Ctenocephalides canis Curtis）、雞蚤（ Ceratophyllus gallinae Schrank）、吸著蚤（ Echidnophaga gallinaceaWestwood）、人蚤（ Pulex irritansLinnaeus）以及其他困擾哺乳動物和禽類的跳蚤。所覆蓋的另外節肢動物害蟲包括：蜘蛛目（Araneae）的蜘蛛，諸如棕色遁蛛（ Loxosceles reclusaGertsch & Mulaik）和黑寡婦毒蛛（ Latrodectus mactansFabricius），以及蚰蜒目（Scutigeromorpha）的蜈蚣，諸如蚰蜒（ Scutigera coleoptrataLinnaeus）。 Agronomic and non-agronomic pests also include: eggs, larvae, nymphs and adults of the order Acari (mites), such as spider mites and red mites of the family Tetranychidae (e.g., European red mite ( Panonychus ulmi Koch , Tetranychus urticae Koch , Tetranychus mcdanieli McGregor ); flat mites of the family Tenuipalpidae (e.g., Mites ( Brevipalpus lewisi McGregor); rust mite and bud mite of the family Eriophyidae and other leaf-feeding mites and mites important in human and animal health, i.e. Epidermophyidae Dust mites (Epidermoptidae), hair follicle mites (Demodicidae), grain mites (Glycyphagidae); ticks, Ixodidae, commonly called hard ticks (eg, deer ticks ( Ixodes scapularis Say), Australian paralytic ticks ( Ixodes holocyclus Neumann), American dog ticks ( Dermacentor variabilis Say), lone star ticks ( Amblyomma americanum Linnaeus)) and ticks of the family Argasidae, commonly called soft ticks (eg , recurrent heat tick ( Ornithodoros turicata ), common chicken tick ( Argas radiatus ); scab mite and itch mite of the families Psoroptidae, Pyemotidae and Sarcoptidae mite); eggs, adults, and larvae of the order Orthoptera, including grasshoppers, locusts, and crickets (e.g., migratory grasshoppers (e.g., Melanoplus sanguinipes Fabricius), M. differentialis Thomas), American grasshoppers (such as Schistocerca americana Drury), desert locust ( Schistocerca gregaria Forskal), migratory locust ( Locusta migratoria Linnaeus) , bush locust ( Zonocerus species), house cricket ( Acheta domesticus Linnaeus), mole crickets (for example, Scapteriscus vicinus Scudder) and South American mole cricket ( Scapteriscus borellii Giglio-Tos )); eggs, adults and larvae of the order Diptera, including leaf miners (e.g. Liriomyza species such as Liriomyza sativae Blanchard), midges, fruit flies (L. Tephritidae), straw flies (e.g. Oscinella frit Linnaeus), soil maggots, houseflies (e.g. Musca domestica Linnaeus), houseflies (e.g. , Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (eg, Stomoxys calcitrans Linnaeus), face flies, horned Horn flies, blow flies (e.g. Chrysomya species, Phormia species) and other muscoid fly pests, horse flies (e.g., Tabanus species), bot flies (e.g., Gastrophilus species, Oestrus species, cattle grubs (e.g., Hypoderma species ), deer flies (e.g., species of the genus Chrysops ), keds (e.g., Melophagus ovinus Linnaeus ) and other Brachycera suborders, mosquitoes ( eg, Aedes species, Anopheles species, Culex species), black flies (eg, Prosimulium species, Simulium species) , biting midges, sand flies, sc iarids) and other Nematocera; eggs, adults, and larvae of Thysanoptera, including Thrips tabaci Lindeman, flower thrips ( Frankliniella species), and Other leaf-feeding thrips; insect pests of the order Hymenoptera, including ants of the family Formicidae, including Camponotus floridanus Buckley, Camponotus ferrugineus Fabricius, Camponotus pennsylvanicus De Geer), white-footed ant ( Technomyrmex albipes fr. Smith), bighead ant ( Pheidole species), ghost ant ( Tapinoma melanocephalum Fabricius); pharaoh ant ( Monomorium pharaonis Linnaeus), small fire ant ( Wasmannia auropunctata Roger), Fire Ant ( Solenopsis geminata Fabricius), Red Fire Ant ( Solenopsis invicta Buren), Argentine Ant ( Iridomyrmex humilis Mayr), Mad Ant ( Paratrechina longicornis Latreille), Pavement Ant ( Tetramorium caespitum Linnaeus), Corn Field Ant ( Lasius alienus Förster) and the sweet house ant ( Tapinoma sessile Say). Other Hymenoptera, including wasps (including carpenter bees), hornets, yellow jackets, wasps, and sawflies ( Neodiprion ) species; Cephus species); insect pests of the order Isoptera, including Termitidae (e.g., Macrotermes species, Odontotermes obesus Rambur), wood termites Kalotermitidae (e.g., Cryptotermes species), and Rhinotermitidae (e.g., Reticulitermes species, Coptotermes species, Heterotermes tenuis Hagen )), eastern underground termites ( Reticulitermes flavipes Kollar ), western underground termites ( Reticulitermes hesperus Bank), Taiwanese milk termites ( Coptotermes formosanus Shiraki), western Indian drywood termites ( Incisitermesimmigrans Snyder ), pink termites ( Cryptotermes brevis Walker), Drywood termites ( Incisitermes snyderi Light), southeastern subterranean termites ( Reticulitermes virginicus Banks), western drywood termites ( Incisitermes minor Hagen), arboreal termites such as Nasutitermes species, and other economically important insect pests of the order Thysanura, such as silverfish ( Lepisma saccharina Linnaeus) and housefish ( Thermobia domestica Packard); insect pests of the order Mallophaga, including head lice ( Pediculus humanus capitis De Geer) , body lice ( Pediculus humanus Linnaeus ), chicken body lice ( Menacanthus stramineus Nitszch ), dog gnawing hair lice ( Trichodectes c anis De Geer), wool lice ( Goniocotes gallinae De Geer ), sheep body lice ( Bovicolaovis Schrank ), short-nosed cattle lice ( Haematopinus eurysternus Nitzsch), long-nosed cattle lice ( Linognathus vituli Linnaeus) and other sucking and Biting parasitic lice; insect pests of the order Siphonoptera, including Eastern mouse flea ( Xenopsylla cheopis Rothschild ), cat flea ( Ctenocephalides felis Bouche ), dog flea ( Ctenocephalides canis Curtis ), chicken flea ( Ceratophyllus gallinae Schrank ), sucker flea ( Ceratophyllus gallinae Schrank ), fleas ( Echidnophaga gallinacea Westwood), human fleas ( Pulex irritans Linnaeus), and other fleas that plague mammals and birds. Additional arthropod pests covered include: spiders of the order Araneae such as brown recluse spiders ( Loxosceles reclusa Gertsch & Mulaik) and black widow spiders ( Latrodectus mactans Fabricius), and centipedes of the order Scutigeromorpha such as ( Scutigera coleoptrata Linnaeus).
儲存穀物的無脊椎害蟲的實例包括平截長蠹（ Prostephanus truncatus）、小穀蠹（ Rhyzopertha dominica）、米象（ Stiophilus oryzae）、玉米象（ Stiophilus zeamais）、豆象（ Callosobruchus maculatus）、赤擬穀盜（ Tribolium castaneum）、穀象（ Stiophilus granarius）、印度穀螟（ Plodia interpunctella）、地中海麵粉甲蟲（ Ephestia kuhniella）和長角扁穀盜或鏽扁穀盜（ Cryptolestis ferrugineus）。 Examples of invertebrate pests of stored grain include the truncated beetle ( Prostephanus truncatus ), small grain beetle ( Rhyzopertha dominica ), rice weevil ( Stiophilus oryzae ), corn weevil ( Stiophilus zeamais ), bean weevil ( Callosobruchus maculatus ), Tribolium castaneum , grain elephant ( Stiophilus granarius ), Indian meal moth ( Plodia interpunctella ), Mediterranean flour beetle ( Ephestia kuhniella ) and long-horned or rusty flat beetle ( Cryptolestis ferrugineus ).
本揭露之化合物還具有針對線蟲綱（Nematoda）、絛蟲綱（Cestoda）、吸蟲綱和棘頭綱（Acanthocephala）的成員的活性，包括經濟上重要的圓線蟲目（Strongylida）、蛔目（Ascaridida）、尖尾目（Oxyurida）、小桿目（Rhabditida）、旋尾目（Spirurida）和嘴刺目（Enoplida）的成員，諸如但不限於經濟上重要的農業害蟲（即，根結線蟲屬（ Meloidogyne）中的根結線蟲、短體線蟲屬（ Pratylenchus）中的根腐線蟲（lesion nematodes）、毛刺線蟲屬（ Trichodorus）中的粗短根線蟲（stubby root nematodes）等）以及動物和人類健康害蟲（即，所有經濟上重要的吸蟲、絛蟲和蛔蟲，諸如馬中的尋常圓線蟲（ Strongylus vulgaris）、犬中的犬弓蛔蟲（ Toxocara canis）、羊中的撚轉血矛線蟲（ Haemonchus contortus）、犬中的犬惡絲蟲（ Dirofilaria immitis Leidy）、馬中的葉狀裸頭絛蟲（ Anoplocephala perfoliata）、反芻動物中的肝片吸蟲（ Fasciola hepatica Linnaeus）等）。 The compounds of the present disclosure are also active against members of the classes Nematoda, Cestoda, Trematodes and Acanthocephala, including the economically important Strongylida, Ascaridida ), members of the orders Oxyurida, Rhabditida, Spirurida and Enoplida, such as but not limited to economically important agricultural pests (i.e., Meloidogyne root-knot nematodes, lesion nematodes in the genus Pratylenchus , stubby root nematodes in the genus Trichodorus, etc.) as well as animal and human health pests (ie, All economically important flukes, tapeworms and roundworms such as Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Dirofilaria immitis Leidy in , Anoplocephala perfoliata in horses, Fasciola hepatica Linnaeus in ruminants, etc.).
本揭露之化合物顯示出針對鱗翅目中的害蟲的特別高的活性（例如，棉葉波紋夜蛾（ Alabama argillaceaHübner）（棉葉蟲）、果樹黃卷蛾（ Archips argyrospilaWalker）（果樹卷葉蛾）、 A. rosanaLinnaeus（歐洲卷葉蛾）以及其他黃卷蛾屬（ Archips）物種、二化螟（ Chilo suppressalisWalker）（稻螟）、稻縱卷葉螟（ Cnaphalocrosis medinalisGuenée，rice leaf roller）、玉米根草螟（ Crambus caliginosellusClemens）（玉米根結網蟲）、早熟禾草螟（ Crambus teterrellusZincken，bluegrass webworm）、蘋果蠹蛾（ Cydia pomonellaLinnaeus，codling moth）、棉斑實蛾（ Earias insulanaBoisduval）（多刺螟蛉蟲）、翠紋鑽夜蛾（ Earias vittellaFabricius）（斑點螟蛉蟲）、棉鈴蟲（ Helicoverpa armigeraHübner）（美洲棉鈴蟲）、穀實夜蛾（ Helicoverpa zeaBoddie）（玉米穗蟲）、煙芽夜蛾（ Heliothis virescensFabricius）（煙青蟲）、草地螟（ Herpetogramma licarsisalisWalker，sod webworm）、葡萄花翅小卷蛾（ Lobesia botranaDenis & Schiffermüller）（葡萄卷葉蛾）、棉紅鈴蟲（ Pectinophora gossypiellaSaunders，pink bollworm）、柑橘潛葉蛾（ Phyllocnistis citrellaStainton，citrus leafminer）、大菜粉蝶（ Pieris brassicaeLinnaeus）（大白粉蝶）、小菜粉蝶（ Pieris rapaeLinnaeus）（小白粉蝶）、小菜蛾（ Plutella xylostellaLinnaeus，diamondback moth）、甜菜夜蛾（ Spodoptera exiguaHübner，beet armyworm）、斜紋夜蛾（ Spodoptera lituraFabricius，tobacco cutworm，cluster caterpillar）、草地貪夜蛾（ Spodoptera frugiperdaJ. E. Smith）（秋夜蛾）、粉紋夜蛾（ Trichoplusia niHübner，cabbage looper）和番茄潛葉蛾（ T uta absolutaMeyrick，tomato leafminer）。 The compounds of the present disclosure show particularly high activity against pests in the order Lepidoptera (for example, Alabama argillacea Hübner (cotton leafworm), Archips argyrospila Walker (fruit tree leaf tortrix) ), A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice borer), Cnaphalocrosis medinalis Guenée, rice leaf roller , Crambus caliginosellus Clemens (corn root-knot worm), Crambus teterrellus Zincken, bluegrass webworm, Cydia pomonella Linnaeus, codling moth, Earias insulana Boisduval ) (spiny bollworm), Earias vittella Fabricius (spotted bollworm), cotton bollworm ( Helicoverpa armigera Hübner) (American bollworm), corn bollworm ( Helicoverpa zea Boddie) (corn earworm ), tobacco bud moth ( Heliothis virescens Fabricius) (tobacco caterpillar), meadow moth ( Herpetogramma licarsisalis Walker, sod webworm), grape leaf tortrix ( Lobesia botrana Denis & Schiffermüller) (vine leaf tortrix), cotton red Pectinophora gossypiella Saunders (pink bollworm), Citrus Leafminer ( Phyllocnistis citrella Stainton, citrus leafminer), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), cabbage moth ( Plutella xylostella Linnaeus, diamondback moth), beet armyworm ( Spodoptera exigua Hübner, beet armyworm ) , armyworm (Spodoptera exigua Hübner, beet armyworm), doptera litura Fabricius, tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J. E. Smith (fall armyworm), Trichoplusia ni Hübner, cabbage looper and tomato leafminer ( T uta absoluta Meyrick, tomato leaf miner).
本揭露之化合物還對來自半翅目的成員具有顯著的活性，該等成員包括：豌豆蚜（ Acyrthosiphon pisumHarris）、豇豆蚜（ Aphis craccivoraKoch）、蠶豆蚜（ Aphis fabaeScopoli）、棉蚜（ Aphis gossypiiGlover）、蘋果蚜（ Aphis pomiDe Geer）、繡線菊蚜（ Aphis spiraecolaPatch）、毛地黃蚜（ Aulacorthum solaniKaltenbach）、草莓蚜（ Chaetosiphon fragaefoliiCockerell）、俄羅斯小麥蚜（ Diuraphis noxiaKurdjumov/Mordvilko）、車前圓尾蚜（ Dysaphis plantagineaPasserini）、蘋果綿蚜（ Eriosoma lanigerumHausmann）、桃大尾蚜（ Hyalopterus pruniGeoffroy）、蘿蔔蚜（ Lipaphis pseudobrassicaeDavis）、麥蚜（ Metopolophium dirhodumWalker）、馬鈴薯蚜（ Macrosiphum euphorbiaeThomas）、桃蚜（ Myzus persicaeSulzer）、萵苣蚜（ Nasonovia ribisnigriMosley）、癭綿蚜屬（ Pemphigus）物種（根蚜（root aphids）和倍蚜（gallaphids））、玉米蚜（ Rhopalosiphum maidisFitch）、禾穀縊管蚜（ Rhopalosiphum padiLinnaeus）、麥二叉蚜（ Schizaphis graminumRondani）、麥長管蚜（ Sitobion avenaeFabricius）、苜蓿斑蚜（ Therioaphis maculataBuckton）、橘二叉蚜（ Toxoptera aurantiiBoyer de Fonscolombe）和褐色橘蚜（ Toxoptera citricidusKirkaldy）；球蚜屬（ Adelges）物種（球蚜（adelgids））；山核桃根瘤蚜（ Phylloxera devastatrixPergande）；煙粉虱、甘薯粉虱（ Bemisia tabaciGennadius）、銀葉粉虱（ Bemisia argentifoliiBellows & Perring）、柑橘粉虱（ Dialeurodes citriAshmead）和溫室粉虱（ Trialeurodes vaporariorumWestwood）；馬鈴薯葉蟬（ Empoasca fabaeHarris）、小褐飛虱（ Laodelphax striatellusFallen）、二點葉蟬（ Macrosteles quadrilineatusForbes）、稻黑尾葉蟬（ Nephotettix cincticepsUhler）、黑尾葉蟬（ Nephotettix nigropictusStål）、褐飛虱（ Nilaparvata lugensStål）、玉米飛虱（ Peregrinus maidisAshmead）、白背飛虱（ Sogatella furciferaHorvath）、稻飛蝨（ Tagosodes orizicolusMuir）、蘋果白葉蟬（ Typhlocyba pomariaMcAtee）、葡萄斑葉蟬屬（Erythroneura）物種（葡萄葉蟬（grape leafhoppers））；週期蟬（ Magicidada septendecimLinnaeus）；吹綿蚧（ Icerya purchasiMaskell）、梨圓蚧（ Quadraspidiotus perniciosusComstock）；柑桔粉蚧（ Planococcus citriRisso）；粉蚧屬（ Pseudococcus）物種（其他粉蚧系群）；梨木虱（ Cacopsylla pyricolaFoerster）、柿木虱（ Trioza diospyriAshmead）。 The disclosed compounds also have significant activity against members from the order Hemiptera, including: pea aphid ( Acyrthosiphon pisum Harris), cowpea aphid ( Aphis craccivora Koch), faba bean aphid ( Aphis fabae Scopoli), cotton aphid ( Aphis gossypii Glover), apple aphid ( Aphis pomi De Geer), spirea aphid ( Aphis spiraecola Patch), foxglove aphid ( Aulacorthum solani Kaltenbach), strawberry aphid ( Chaetosiphon fragaefolii Cockerell), Russian wheat aphid ( Diuraphis noxia Kurdjumov/Mordvilko) , Dysaphis plantaginea Passerini, Eriosoma lanigerum Hausmann, Hyalopterus pruni Geoffroy, Lipaphis pseudobrassicae Davis, Metopolophium dirhodum Walker, and Macrosiphum euphorbiae Thomas), green peach aphid ( Myzus persicae Sulzer), lettuce aphid ( Nasonovia ribisnigri Mosley), pemphigus species (root aphids and gallaphids), corn aphid ( Rhopalosiphum maidis Fitch) , Rhopalosiphum padi Linnaeus, Schizaphis graminum Rondani, Sitobion avenae Fabricius, Therioaphis maculata Buckton, Toxoptera aurantii Boyer de Fonscolombe) and brown orange aphid ( Toxoptera citricidus Kirkaldy); Adelges species (adelgids); hickory phylloxera ( Phylloxera devastatrix Pergande); whitefly, sweet potato whitefly ( Bemisia tabaci Gennadius), silverleaf whitefly ( Bemisia argentifolii Bellows & Perring), citrus whitefly ( Dialeurodes citri Ashmead) and greenhouse whitefly ( Trialeurodes vaporariorum Westwood); potato leafhopper ( Empoasca fabae Harris), small brown planthopper ( Laodelphax striatellus Fallen), two-point leafhopper ( Macrosteles quadrilineatus Forbes), rice black-tailed leafhopper ( Nephotettix cincticeps Uhler), black-tailed leafhopper ( Nephotettix nigropictus Stål), brown planthopper ( Nilaparvata lugens Stål), corn planthopper ( Peregrinus maidis Ashmead ), white-backed planthopper ( Sogatella furcifera Horvath), rice planthopper ( Tagosodes orizicolus Muir), apple leafhopper ( Typhlocyba pomaria McAtee), grape leafhopper (Erythroneura) species (grape leafhoppers); cycle Cicada ( Magicidada septendecim Linnaeus); Icerya purchasi Maskell, Quadraspidiotus perniciosus Comstock; Citrus mealybug ( Planococcus citri Risso); Pseudococcus species (other mealybug lineages); Pear psyllid ( Cacopsylla pyricola Foerster), persimmon psyllid ( Trioza diospyri Ashmead).
本揭露之化合物還對來自半翅目的成員具有活性，該等成員包括：稻綠蝽（ Acrosternum hilareSay）、南瓜緣蝽（ Anasa tristisDe Geer）、麥長蝽（ Blissus leucopterus leucopterusSay）、溫帶臭蟲（ Cimex lectulariusLinnaeus）、棉網蝽（ Corythuca gossypiiFabricius）、番茄蝽（ Cyrtopeltis modestaDistant）、棉紅蝽（ Dysdercus suturellusHerrich-Schäffer）、褐臭蝽（ Euchistus servusSay）、單斑蝽（ Euchistus variolariusPalisot de Beauvois）、 Graptosthetus屬物種（長蝽系群）、茶翅蝽（ Halymorpha halysStål）、松葉根蝽（ Leptoglossus corculusSay）、美國牧草盲蝽（ Lygus lineolarisPalisot de Beauvois）、南方綠蝽（ Nezara viridulaLinnaeus）、稻褐蝽（ Oebalus pugnaxFabricius）、大馬利筋長蝽（ Oncopeltus fasciatusDallas）、棉盲蝽（ Pseudatomoscelis seriatusReuter）。由本揭露之化合物防治的其他昆蟲目包括纓翅目（例如，西花薊馬（ Frankliniella occidentalisPergande）、柑橘薊馬（ Scirthothrips citriMoulton）、大豆薊馬（ Sericothrips variabilisBeach）和洋蔥薊馬；以及鞘翅目（例如，科羅拉多馬鈴薯甲蟲、墨西哥豆瓢蟲（ Epilachna varivestisMulsant）以及叩甲屬（ Agriotes）、 Athous屬或丘胸叩甲屬（ Limonius）的金針蟲）。 The compounds of the present disclosure are also active against members from the order Hemiptera, including: Acrosternum hilare Say, Anasa tristis De Geer, Blissus leucopterus leucopterus Say, temperate bedbugs ( Cimex lectularius Linnaeus), Corythuca gossypii Fabricius, Cyrtopeltis modesta Distant, Dysdercus suturellus Herrich-Schäffer, Euchistus servus Say, Euchistus variolarius Palisot de Beauvois), Graptosthetus species (Long bug lineage), tea-winged bug ( Halymorpha halys Stål), pine leaf root bug ( Leptoglossus corculus Say), American grass bug ( Lygus lineolaris Palisot de Beauvois), southern green bug ( Nezara viridula Linnaeus), rice brown bug ( Oebalus pugnax Fabricius), large milkweed bug ( Oncopeltus fasciatus Dallas), cotton bug ( Pseudatomoscelis seriatus Reuter). Other insect orders controlled by the compounds of the present disclosure include Thysanoptera (e.g., Frankliniella occidentalis Pergande, Scirthothrips citri Moulton, Soybean Thrips ( Sericothrips variabilis Beach) and Onion Thrips; and Elytra order (e.g., Colorado potato beetle, Mexican bean beetle ( Epilachna varivestis Mulsant), and needle beetles of the genera Agriotes , Athous , or Limonius ).
值得注意的是本揭露之化合物用於防治銀葉粉虱（ Bemisia argentifolii）的用途。值得注意的是本揭露之化合物用於防治棉蚜( Aphis gossypii)的用途。值得注意的是本揭露之化合物用於防治桃蚜的用途。值得注意的是本揭露之化合物用於防治小菜蛾（ Plutella xylostella）的用途。 Of note is the use of the disclosed compounds for controlling whitefly ( Bemisia argentifolii ). Of note is the use of the disclosed compounds for controlling cotton aphids ( Aphis gossypii ). Of note is the use of the disclosed compounds for controlling green peach aphids. Noteworthy is the use of the disclosed compounds for controlling diamondback moth ( Plutella xylostella ).
本揭露之化合物還可用於增加作物植株的活力。該方法包括使作物植株（例如，葉子、花、果實或根）或生長出作物植株的種子與足以實現期望的植株活力效果的量（即生物學有效量）式 1的化合物接觸。典型地，式 1的化合物以配製的組成物施加。儘管式 1的化合物通常直接施加於作物植株或其種子，但該等化合物也可施加於作物植株的所在地，即作物植株的環境，特別是足夠接近以允許式 1的化合物遷移到作物植株的環境部分。與該方法相關的所在地最通常包括生長介質（即為植株提供營養素的介質），典型地是其中生長植株的土壤。因此，為了增加作物植株的活力對作物植株的處理包括使作物植株、生長出作物植株的種子或作物植株的所在地與生物學有效量的式 1的化合物接觸。 The compounds of the present disclosure can also be used to increase the vigor of crop plants. The method comprises contacting a crop plant (eg, leaves, flowers, fruit or roots) or seeds from which a crop plant has grown with an amount of a compound of Formula 1 sufficient to achieve the desired plant vigor effect (ie, a biologically effective amount). Typically, the compound of formula 1 is applied as a formulated composition. Although the compounds of formula 1 are usually applied directly to the crop plants or their seeds, the compounds may also be applied to the locus of the crop plants, i.e. the environment of the crop plants, especially an environment close enough to allow the compound of formula 1 to migrate to the crop plants part. The locus associated with the method most often includes a growing medium (ie, a medium that provides nutrients to the plants), typically soil in which the plants are grown. Thus, the treatment of crop plants to increase the vigor of the crop plants comprises contacting the crop plants, the seeds from which the crop plants grew or the locus of the crop plants with a biologically effective amount of a compound of formula 1 .
增加作物活力可導致以下觀察到的效果中的一項或多項：(a) 如藉由優異的種子發芽、作物出苗和作物密度（stand）展示的最佳作物栽培（establishment）；(b) 如藉由快速且健壯的葉生長（例如，藉由葉面積指數測量）、植株高度、分蘗數（例如，對於稻）、根群和作物的營養體的總乾重展示的增強的作物生長；(c) 如藉由開花時間、開花持續時間、花的數目、總生物量積聚（即產量）和/或果實或穀物的產品等級可銷售性（即產品質）展示的改善的作物產量；(d) 增強的作物耐受或預防植物病害感染和節肢動物、線蟲或軟體動物害蟲侵害的能力；以及 (e) 增加的作物耐受環境脅迫（諸如暴露於極端熱量、次最佳水分或植物性毒素化學品）的能力。Increased crop vigor may result in one or more of the following observed effects: (a) optimal crop establishment as demonstrated by superior seed germination, crop emergence and crop stand; (b) as demonstrated by superior seed germination, crop emergence and crop stand; Enhanced crop growth demonstrated by rapid and robust leaf growth (e.g., as measured by leaf area index), plant height, tiller number (e.g., for rice), root mass, and total dry weight of the plant's vegetative body;( c) improved crop yield as demonstrated by flowering time, flowering duration, number of flowers, total biomass accumulation (i.e. yield) and/or product grade marketability of fruit or grain (i.e. product quality); (d ) increased crop resistance to or protection against plant disease infection and arthropod, nematode or mollusc pest infestation; and (e) increased crop tolerance to environmental stresses such as exposure to extreme heat, sub-optimal moisture, or phytotoxins chemicals) capabilities.
與未經處理的植株相比，本揭露之化合物可藉由殺死植食性無脊椎害蟲或以其他方式防止植食性無脊椎害蟲在植株環境中的取食來增加經處理的植株的活力。在不存在植食性無脊椎害蟲的此類防治的情況下，害蟲藉由消耗植物組織或汁液，或傳播植物病原體諸如病毒來降低植株活力。甚至在不存在植食性無脊椎害蟲的情況下，本揭露之化合物可藉由改變植株的代謝來增加植株活力。通常，如果植株生長在非理想的環境中，即包含一個或多個不利於植株實現其在理想環境中應表現出的完全遺傳潛力的方面的環境中，那麼作物植株的活力將藉由用本揭露之化合物處理該植株最顯著地增加。Compounds of the present disclosure can increase the vigor of treated plants compared to untreated plants by killing or otherwise preventing feeding of phytophagous invertebrate pests in the plant environment. In the absence of such control by phytophagous invertebrate pests, the pests reduce plant vigor by consuming plant tissue or sap, or spreading plant pathogens such as viruses. Even in the absence of phytophagous invertebrate pests, compounds of the present disclosure can increase plant vigor by altering plant metabolism. Generally, if a plant is grown in a non-ideal environment, that is, an environment that contains one or more aspects that are not conducive to the plant achieving its full genetic potential that it should exhibit in an ideal environment, the vigor of the crop plant will be improved by using this Treatment of the plants with the disclosed compounds resulted in the most significant increase.
值得注意的是用於增加作物植株活力的本發明之方法，其中該作物植株在包括植食性無脊椎害蟲的環境中生長。還值得注意的是用於增加作物植株活力的本發明之方法，其中該作物植株在不包括植食性無脊椎害蟲的環境中生長。還值得注意的是用於增加作物植株活力的本發明之方法，其中該作物植株在包括少於支持作物植株生長的理想水分量的水分量的環境中生長。值得注意的是用於增加作物植株活力的本發明之方法，其中該作物係稻。還值得注意的是用於增加作物植株活力的本發明之方法，其中該作物係玉蜀黍（玉米）。還值得注意的是用於增加作物植株活力的本發明之方法，其中該作物係大豆。Of note are the methods of the invention for increasing the vigor of crop plants grown in an environment that includes herbivorous invertebrate pests. Also of note is the method of the present invention for increasing the vigor of crop plants, wherein the crop plants are grown in an environment that does not include herbivorous invertebrate pests. Also of note are the methods of the invention for increasing the vigor of crop plants, wherein the crop plants are grown in an environment comprising less than the ideal amount of moisture to support the growth of the crop plants. Of note is the method of the present invention for increasing plant vigor of a crop, wherein the crop is rice. Also of note is the method of the present invention for increasing plant vigor of a crop, wherein the crop is maize (maize). Also of note is the method of the present invention for increasing plant vigor of a crop, wherein the crop is soybean.
本揭露之化合物還可與一種或多種其他生物學活性化合物或藥劑混合以形成多組分殺害蟲劑，從而賦予甚至更廣譜的農學和非農學效用，該等生物學活性化合物或藥劑包括殺昆蟲劑、殺真菌劑、殺線蟲劑、殺菌劑、殺蟎劑、除草劑、除草劑安全劑、生長調節劑諸如昆蟲蛻皮抑制劑和生根刺激劑、化學不育劑、化學資訊素、驅蟲劑、引誘劑、資訊素、取食刺激劑、其他生物學活性化合物或昆蟲病原細菌、病毒或真菌。因此，本揭露還關於包含生物學有效量的式 1的化合物、至少一種附加組分和至少一種附加生物學活性化合物或藥劑的組成物，該至少一種附加組分選自由表面活性劑、固體稀釋劑和液體稀釋劑組成之群組。對於本揭露之混合物，可將其他生物學活性化合物或藥劑與本發明化合物（包括式 1的化合物）一起配製以形成預混物，或者其他生物學活性化合物或藥劑可與本發明化合物（包括式 1的化合物）分開配製，並且在施加前將這兩種製劑組合在一起（例如，在噴霧槽中），或替代性地，將這兩種製劑依次施加。 Compounds of the present disclosure may also be mixed with one or more other biologically active compounds or agents, including Insecticides, fungicides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molt inhibitors and rooting stimulators, chemical sterilants, chemical semiochemicals, insect repellants agents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, viruses or fungi. Accordingly, the present disclosure also relates to compositions comprising a biologically effective amount of a compound of formula 1 , at least one additional component selected from the group consisting of surfactants, solid diluents, and at least one additional biologically active compound or agent. The group consisting of a liquid diluent and a liquid diluent. For the mixtures of the present disclosure, other biologically active compounds or agents may be formulated with compounds of the present invention (including compounds of formula 1 ) to form a premix, or other biologically active compounds or agents may be combined with compounds of the present invention (including compounds of formula 1) 1 ) separately and the two formulations are combined (eg, in a spray tank) prior to application, or alternatively, the two formulations are applied sequentially.
可與本揭露之化合物一起配製的此類生物學活性化合物或藥劑的實例係殺昆蟲劑，諸如阿巴汀、乙醯甲胺磷、滅蟎醌、啶蟲脒、氟丙菊酯、阿克那比（acynonapyr）、雙丙環蟲酯（[(3 S,4 R,4a R,6 S,6a S,12 R,12a S,12b S)-3-[(環丙基羰基)氧基]-1,3,4,4a,5,6,6a,12,12a,12b-十氫-6,12-二羥基-4,6a,12b-三甲基-11-側氧基-9-(3-吡啶基)-2 H,11 H-萘并[2,1- b]哌喃并[3,4- e]哌喃-4-基]甲基環丙烷甲酸酯）、磺胺蟎酯、雙甲脒、阿維菌素、印楝素、保棉磷、丙硫克百威、殺蟲磺、苯吡氧嘧啶（benzpyrimoxan）、聯苯菊酯、κ-聯苯菊酯、聯苯肼酯、雙三氟蟲脲、硼酸鹽、溴蟲氟苯雙醯胺（broflanilide）、噻𠯤酮、硫線磷、甲萘威、克百威、殺螟丹、伐蟲脒、氯蟲苯甲醯胺、溴蟲腈、氟啶脲、氯丙炔菊酯（chloroprallethrin）、毒死蜱、毒死蜱-e（chlorpyrifos-e）、甲基毒死蜱、環蟲醯肼、四蟎𠯤、右旋反式氯丙炔菊酯（chloroprallethrin）、噻蟲胺、溴氰蟲醯胺（3-溴-1-(3-氯-2-吡啶基)- N-[4-氰基-2-甲基-6-[(甲基胺基)羰基]苯基]-1 H-吡唑-5-甲醯胺）、環溴蟲醯胺（3-溴- N-[2-溴-4-氯-6-[[(1-環丙基乙基)胺基]羰基]苯基]-1-(3-氯-2-吡啶基)-1 H-吡唑-5-甲醯胺）、乙氰菊酯、環氧蟲啶（(5 S,8 R)-1-[(6-氯-3-吡啶基)甲基]-2,3,5,6,7,8-六氫-9-硝基-5,8-環氧基-1 H-咪唑并[1,2- a]氮呯）、腈吡蟎酯、丁氟蟎酯、氟氯氰菊酯、高效氟氯氰菊、氯氟氰蟲醯胺、三氟氯氰菊酯、精高效氯氟氰菊酯、高效氯氟氰菊酯、氯氰菊酯、順式氯氰菊酯、ζ-氯氰菊酯、滅蠅胺、溴氰菊酯、丁醚脲、二𠯤磷、敵克美施（dicloromesotiaz）、狄氏劑、除蟲脲、四氟甲醚菊酯、殺蟲雙、樂果、𠯤蟲唑醯胺、呋蟲胺、苯蟲醚、甲胺基阿維菌素、甲胺基阿維菌素苯甲酸鹽、硫丹、高氰戊菊酯、乙蟲腈、醚菊酯、ε-甲氧苄氟菊酯、乙蟎唑、苯丁錫、殺螟硫磷、苯硫威、苯氧威、甲氰菊酯、氰戊菊酯、氟蟲腈、氟麥托醌（2-乙基-3,7-二甲基-6-[4-(三氟甲氧基)苯氧基]-4-喹啉基甲基碳酸酯）、氟啶蟲醯胺、三氟咪啶醯胺、氟蟲雙醯胺、氟氰戊菊酯、嘧蟲胺、氟蟲脲、氟菌蟎酯（(α E)-2-[[2-氯-4-(三氟甲基)苯氧基]甲基]-α-(甲氧基亞甲基)苯乙酸甲酯）、氟速芬（5-氯-2-[(3,4,4-三氟-3-丁烯-1-基)磺醯基]噻唑）、氟己芬、氟吡菌醯胺、丁蟲腈（flupiprole）（1-[2,6-二氯-4-(三氟甲基)苯基]-5-[(2-甲基-2-丙烯-1-基)胺基]-4-[(三氟甲基)亞磺醯基]-1 H-吡唑-3-甲腈）、氟吡呋喃酮（4-[[(6-氯-3-吡啶基)甲基](2,2-二氟乙基)胺基]-2(5 H)-呋喃酮）、氟必靈（flupyrimin）、氟胺氰菊酯、氟胺氰戊菊酯、氟㗁唑醯胺、地蟲硫磷、伐蟲脒、噻唑膦、精高效氯氟氰菊酯、氯蟲醯肼、七氟甲醚菊酯（[2,3,5,6-四氟-4-(甲氧基甲基)苯基]甲基 2,2-二甲基-3-[(1 Z)-3,3,3-三氟-1-丙烯-1-基]環丙烷羧酸酯）、氟鈴脲、噻蟎酮、氟蟻腙、吡蟲啉、茚蟲威、殺蟲肥皂、異丙胺磷、異㗁唑蟲醯胺、κ-七氟菊酯、高效氯氟氰菊酯、虱蟎脲、馬拉硫磷、氯氟醚菊酯（[2,3,5,6-四氟-4-(甲氧基甲基)苯基]甲基 (1 R,3 S)-3-(2,2-二氯乙烯基)-2,2-二甲基環丙烷羧酸酯）、氰氟蟲腙、四聚乙醛、甲胺磷、殺撲磷、甲硫威、滅多威、烯蟲酯、甲氧滴滴涕、甲氧苄氟菊酯、甲氧蟲醯肼、ε-甲氧苄氟菊酯、ε-氟氯氰菊酯（momfluorothrin）、久效磷、單氟菊酯（[2,3,5,6-四氟-4-(甲氧基甲基)苯基]甲基 3-(2-氰基-1-丙烯-1-基)-2,2-二甲基環丙烷羧酸酯）、菸鹼、烯啶蟲胺、硝蟲噻𠯤、氟醯脲、多氟脲、殺線威、苯并㗁唑（oxazosulfyl）、對硫磷、甲基對硫磷、氯菊酯、甲拌磷、伏殺硫磷、亞胺硫磷、磷胺、抗蚜威、丙溴磷、丙氟菊酯、炔蟎特、丙苯烴菊酯、吡氟丁醯胺（1,3,5-三甲基- N-(2-甲基-1-氧丙基)- N-[3-(2-甲基丙基)-4-[2,2,2-三氟-1-甲氧基-1-(三氟甲基)乙基]苯基]-1 H-吡唑-4-甲醯胺）、吡蚜酮、啶吡唑蟲胺、除蟲菊素、噠蟎靈、啶蟲丙醚、吡氟喹蟲唑、嘧蟎胺（(α E)-2-[[[2-[(2,4-二氯苯基)胺基]-6-(三氟甲基)-4-嘧啶基]氧基]甲基]-α-(甲氧基亞甲基)苯乙酸甲酯）、吡唑蟲啶、吡丙醚、魚藤酮、蘭尼鹼、氟矽菊酯、乙基多殺菌素、多殺菌素、螺蟎酯、螺甲蟎酯、甲氧哌啶乙酯（spiropidion）、螺蟲乙酯、硫丙磷、氟啶蟲胺腈（ N-[甲基氧化物[1-[6-(三氟甲基)-3-吡啶基]乙基]-λ 4-亞磺胺基]氰胺）、蟲醯肼、吡蟎胺、氟苯脲、七氟菊酯、κ-七氟菊酯、特丁硫磷、四氯蟲醯胺、殺蟲畏、胺菊酯、四氟醚菊酯（[2,3,5,6-四氟-4-(甲氧基甲基)苯基]甲基 2,2,3,3-四甲基環丙烷羧酸酯）、四唑蟲醯胺、噻蟲啉、噻蟲𠯤、硫雙威、殺蟲雙、噻唑沙芬（3-苯基-5-(2-噻吩基)-1,2,4-㗁二唑）、唑蟲醯胺、四溴菊酯、唑蚜威、敵百蟲、三氟苯嘧啶（2,4-二側氧基-1-(5-嘧啶基甲基)-3-[3-(三氟甲基)苯基]-2 H-吡啶并[1,2- a]嘧啶內鹽）、殺鈴脲、替環吡唑弗（tyclopyrazoflor）、高效氯氰菊酯、蘇力菌δ-內毒素、昆蟲病原細菌、昆蟲病原病毒或昆蟲病原真菌。 Examples of such biologically active compounds or agents that may be formulated with the compounds of the present disclosure are insecticides such as abatine, acephate, acequinone, acetamiprid, fluprothrin, acetamiprid, That than (acynonapyr), dipropteride ([(3 S ,4 R ,4a R ,6 S ,6a S ,12 R ,12a S ,12b S )-3-[(cyclopropylcarbonyl)oxy ]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9- (3-pyridyl)-2 H ,11 H -naphtho[2,1- b ]pyrano[3,4- e ]pyran-4-yl]methylcyclopropanecarboxylate), sulfamethasone ester, amitraz, abamectin, azadirachtin, acetophos, carbosulfan, benzpyrimoxan, benzpyrimoxan, bifenthrin, kappa-bifenthrin, bifenthrin Phenylhydrazinate, bistrififluben, borate, broflanilide, thiophene, sulfaphos, carbaryl, carbofuran, cartap, fenfenprid, chlorantraniliprole Benzamide, chlorfenapyr, chlorfluazuron, chloroprallethrin, chlorpyrifos, chlorpyrifos-e (chlorpyrifos-e), chlorpyrifos-methyl, chlorpyrifos-e, tetramite, dextrotrans Chloroprallethrin, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridyl) -N- [4-cyano-2-methyl-6 -[(methylamino)carbonyl]phenyl]-1 H -pyrazole-5-formamide), cyclobromide (3-bromo- N- [2-bromo-4-chloro-6- [[(1-cyclopropylethyl)amino]carbonyl]phenyl]-1-(3-chloro-2-pyridyl)-1 H -pyrazole-5-carboxamide), promethrin , Cyclopyrid ((5 S ,8 R )-1-[(6-chloro-3-pyridyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro -5,8-epoxy-1 H -imidazo[1,2- a ]azepam), cyfenpyrid, cyflufen, cyfluthrin, beta-cyfluthrin, chlorofluorocytraniliprole , cyhalothrin, refined high-efficiency cyhalothrin, high-efficiency cyhalothrin, cypermethrin, cis-cypermethrin, ζ-cypermethrin, cyromazine, deltamethrin, diafenthiuron, bis-cypermethrin, dicromethrin (diclomesotiaz), dieldrin, diflubenzuron, perfluthrin, dimehypo, dimethoate, chlorpyramid, dinotefuran, diphenoxyfen, emamectin, methylamine Abamectin benzoate, endosulfan, esfenvalerate, ethiprole, etofenproxil, ε-methoxyfluthrin, etoxazole, fenbutatin, fenitrothion, benzene Thiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flumetorquinone (2-ethyl-3,7-dimethyl-6-[4-(trifluoromethoxy )phenoxy]-4-quinolylmethyl carbonate), sulfonicamid, triflumimid, sulfflubendiamide, flucyvalerate, pyrimidamid, flubenzuron, Flufenofen ((α E )-2-[[2-chloro-4-(trifluoromethyl)phenoxy]methyl]-α-(methoxymethylene)phenylacetic acid methyl ester), Fluprofen (5-Chloro-2-[(3,4,4-Trifluoro-3-buten-1-yl)sulfonyl]thiazole), Fluprofen, Fluopyram, Tepronil (flupiprole)(1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methyl-2-propen-1-yl)amino]-4-[ (trifluoromethyl)sulfinyl]-1 H -pyrazole-3-carbonitrile), fluoropyrfurone (4-[[(6-chloro-3-pyridyl)methyl](2,2 -difluoroethyl)amino]-2(5 H )-furanone), flupyrimin, fluvalinate, fluvalinate, fluoxazolamide, tefenthion , Falamiprid, Thiazophosphine, Beta-cyhalothrin, Chlorantraniliprozine, Sefluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)benzene base]methyl 2,2-dimethyl-3-[(1 Z )-3,3,3-trifluoro-1-propen-1-yl]cyclopropanecarboxylate), hexaflumuron, thiazide Ketone, hydrazone, imidacloprid, indoxacarb, insecticidal soap, isopropylphos, isofenpyrid, kappa-tefluthrin, lambda-cyhalothrin, lufenuron, malathion, Fluofethrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl(1 R ,3 S )-3-(2,2-dichloroethylene base)-2,2-dimethylcyclopropane carboxylate), metaflumizone, metaldehyde, methamidophos, methafos, methiocarb, methomyl, methoprene, methoxychlor, Methofluthrin, methoxyfluid, ε-methoxyfluthrin, ε-cyfluthrin (momfluorothrin), monocrotophos, monofluthrin ([2,3,5,6-tetrafluoro -4-(methoxymethyl)phenyl]methyl 3-(2-cyano-1-propen-1-yl)-2,2-dimethylcyclopropanecarboxylate), nicotine, alkene Acetamid, nitrocarburate, fluorinated urea, polyflururon, oxazocarb, oxazosulfyl, parathion, methyl parathion, permethrin, phorate, sulfoxasulfur Phosphorus, imophos, phosphamide, pirimicarb, profenofos, profluthrin, propargate, profenthrin, pyrflubutamide (1,3,5-trimethyl- N -(2-methyl-1-oxypropyl) -N- [3-(2-methylpropyl)-4-[2,2,2-trifluoro-1-methoxy-1-(tri Fluoromethyl) ethyl] phenyl] -1 H -pyrazole-4-carboxamide), pymetrozine, pyrethrin, pyrethrin, pyridaben, pyridalate, pyridoxine Fenconazole, pyrimidinyl ((α E )-2-[[[2-[(2,4-dichlorophenyl)amino]-6-(trifluoromethyl)-4-pyrimidinyl]oxy Base] methyl]-α-(methoxy Methylene) methyl phenylacetate), pyraclopyr, pyriproxyfen, rotenone, ryanodine, flusalthrin, spinosad, spinosad, spirodiclofen, spiromethin, formazan Oxypiperidine ethyl ester (spiropidion), spirotetramat, thioprofos, sulfoxaflor ( N- [methyl oxide [1-[6-(trifluoromethyl)-3-pyridyl]B base]-λ 4 -sulfinylamino]cyanamide), tebufenhydrazine, tebufenpyrad, hexafenuron, tefluthrin, κ-tefluthrin, terbufos, tetraclofenamide, Tetramethrin, tetramethrin, perfluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 2,2,3,3-tetramethyl Cyclopropane carboxylate), Tetrazolomid, Thiacloprid, Thiacolopyrid, Thiodicarb, Dimehypo, Thiazoliferin (3-phenyl-5-(2-thienyl)-1,2 ,4-Oxadiazole), Fenpyridam, Perbromethrin, Furamicarb, Trichlorfon, Trifluoropyrimidine (2,4-Dioxo-1-(5-Pyrimidinylmethyl) -3-[3-(trifluoromethyl)phenyl] -2H -pyrido[1,2- a ]pyrimidine inner salt), triflumuron, tyclopyrazoflor, beta-cypermethrin, threo Bacteria delta-endotoxin, entomopathogenic bacteria, entomopathogenic viruses or entomopathogenic fungi.
值得注意的是殺昆蟲劑，諸如阿巴汀（abamectin）、啶蟲脒（acetamiprid）、氟丙菊酯（acrinathrin）、阿克那比（acynonapyr）、雙丙環蟲酯（afidopyropen）、雙甲脒（amitraz）、阿維菌素（avermectin）、印楝素（azadirachtin）、丙硫克百威（benfuracarb）、殺蟲磺（bensultap）、聯苯菊酯（bifenthrin）、噻𠯤酮（buprofezin）、溴蟲氟苯雙醯胺（broflanilide）、硫線磷（cadusafos）、甲萘威（carbaryl）、殺螟丹（cartap）、氯蟲苯甲醯胺（chlorantraniliprole）、右旋反式氯丙炔菊酯（chloroprallethrin）、溴蟲腈（chlorfenapyr）、毒死蜱（chlorpyrifos）、噻蟲胺（clothianidin）、溴氰蟲醯胺（cyantraniliprole）、環溴蟲醯胺（cyclaniliprole）、乙氰菊酯（cycloprothrin）、氟氯氰菊酯（cyfluthrin）、高效氟氯氰菊（beta-cyfluthrin）、三氟氯氰菊酯（cyhalothrin）、精高效氯氟氰菊酯（gamma-cyhalothrin）、高效氯氟氰菊酯（lambda-cyhalothrin）、氯氰菊酯（cypermethrin）、順式氯氰菊酯（alpha-cypermethrin）、ζ-氯氰菊酯（zeta-cypermethrin）、滅蠅胺（cyromazine）、溴氰菊酯（deltamethrin）、狄氏劑（dieldrin）、呋蟲胺（dinotefuran）、苯蟲醚（diofenolan）、甲胺基阿維菌素（emamectin）、硫丹（endosulfan）、ε-甲氧苄氟菊酯（epsilon-metofluthrin）、高氰戊菊酯（esfenvalerate）、乙蟲腈（ethiprole）、醚菊酯（etofenprox）、乙蟎唑（etoxazole）、殺螟硫磷（fenitrothion）、苯硫威（fenothiocarb）、苯氧威（fenoxycarb）、氰戊菊酯（fenvalerate）、氟蟲腈（fipronil）、氟麥托醌（flometoquin）、氟㗁唑醯胺（fluxametamide）、氟啶蟲醯胺（flonicamid）、氟蟲雙醯胺（flubendiamide）、氟噻蟲碸（fluensulfone）、氟蟲脲（flufenoxuron）、氟菌蟎酯（flufenoxystrobin）、聯氟碸（flufensulfone）、丁蟲腈（flupiprole）、氟必靈（flupyrimin）、氟吡呋喃酮（flupyradifurone）、氟胺氰菊酯（fluvalinate）、伐蟲脒（formetanate）、噻唑膦（fosthiazate）、精高效氯氟氰菊酯（gamma-cyhalothrin）、七氟甲醚菊酯（heptafluthrin）、氟鈴脲（hexaflumuron）、氟蟻腙（hydramethylnon）、吡蟲啉（imidacloprid）、茚蟲威（indoxacarb）、異㗁唑蟲醯胺（isocycloseram）、κ-七氟菊酯（kappa-tefluthrin）、高效氯氟氰菊酯（lambda-cyhalothrin）、虱蟎脲（lufenuron）、氯氟醚菊酯（meperfluthrin）、氰氟蟲腙（metaflumizone）、甲硫威（methiodicarb）、滅多威（methomyl）、烯蟲酯（methoprene）、甲氧蟲醯肼（methoxyfenozide）、甲氧苄氟菊酯（metofluthrin）、單氟菊酯（monofluorothrin）、烯啶蟲胺（nitenpyram）、硝蟲噻𠯤（nithiazine）、氟醯脲（novaluron）、殺線威（oxamyl）、吡氟丁醯胺（pyflubumide）、吡蚜酮（pymetrozine）、除蟲菊素（pyrethrin）、噠蟎靈（pyridaben）、啶蟲丙醚（pyridalyl）、嘧蟎胺（pyriminostrobin）、吡丙醚（pyriproxyfen）、蘭尼鹼（ryanodine）、乙基多殺菌素（spinetoram）、多殺菌素（spinosad）、螺蟎酯（spirodiclofen）、螺甲蟎酯（spiromesifen）、螺蟲乙酯（spirotetramat）、氟啶蟲胺腈（sulfoxaflor）、蟲醯肼（tebufenozide）、胺菊酯（tetramethrin）、四氟醚菊酯（tetramethylfluthrin）、噻蟲啉（thiacloprid）、噻蟲𠯤（thiamethoxam）、硫雙威（thiodicarb）、殺蟲雙（thiosultap-sodium）、四溴菊酯（tralomethrin）、唑蚜威（triazamate）、三氟苯嘧啶（triflumezopyrim）、殺鈴脲（triflumuron）、替環吡唑弗（tyclopyrazoflor）、ζ-氯氰菊酯（zeta-cypermethrin）、蘇力菌δ-內毒素、蘇力菌的所有菌株和核多角體病毒的所有毒株。Of note are insecticides such as abamectin, acetamiprid, acrinathrin, acynonapyr, afidopyropen, bimethyl Amitraz, avermectin, azadirachtin, benfuracarb, bensultap, bifenthrin, buprofezin , broflanilide, cadusafos, carbaryl, cartap, chlorantraniliprole, dextro-trans chlorpropyne Chloroprallethrin, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cycloprothrin , cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran ), diofenolan, emamectin, endosulfan, epsilon-metofluthrin, esfenvalerate, B Ethiprole, etofenprox, etoxazole, fenitrothion, fenothiocarb, fenoxycarb, fenvalerate, Fipronil, flometoquin, fluxametamide, flonicamid , flubendiamide, fluensulfone, flufenoxuron, flufenoxystrobin, flufensulfone, flupiprole, flubiline (flupyrimin), flupyradifurone, fluvalinate, formetanate, fosthiazate, gamma-cyhalothrin, heptafluoromethyl Heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, isocycloseram, kappa-tefluthrin ( kappa-tefluthrin), lambda-cyhalothrin, lufenuron, meperfluthrin, metaflumizone, methiodicarb, methomyl (methomyl), methoprene, methoxyfenozide, metofluthrin, monofluorothrin, nitenpyram, nitrate (nithiazine), novaluron, oxamyl, pyflubumide, pymetrozine, pyrethrin, pyridaben, pyrethrin Pyridalyl, pyriminostrobin, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen , spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiophene thiacloprid, thiamethoxam, thiodicarb, Thiosultap-sodium, tralomethrin, triazamate, triflumezopyrim, triflumuron, tyclopyrazoflor, ζ-cypermethrin (zeta-cypermethrin), S. thaliana delta-endotoxin, all strains of S. thaliana and all strains of nuclear polyhedrosis virus.
用於與本揭露之化合物混合的生物劑的一個實施方式包括昆蟲病原細菌，諸如蘇力菌，以及藉由CellCap ®製程製備的蘇力菌的包封δ-內毒素，諸如MVP ®和MVPII ®生物殺昆蟲劑（CellCap ®、MVP ®和MVPII ®係Mycogen Corporation, Indianapolis, Indiana, USA [麥可根公司, 印弟安納波里斯，印第安那州，USA]的商標）；昆蟲病原真菌，諸如綠僵菌（green muscardine fungus）；和昆蟲病原（自然存在的和遺傳改性的）病毒，包括桿狀病毒、核多角體病毒（NPV），諸如穀實夜蛾核多角體病毒（HzNPV）、芹菜夜蛾核多角體病毒（ Anagrapha falciferanucleopolyhedrovirus，AfNPV）；以及顆粒體病毒（GV），諸如蘋果蠹蛾顆粒體病毒（ Cydia pomonellagranulosis virus，CpGV）。 One embodiment of a biological agent for use in admixture with a compound of the present disclosure includes entomopathogenic bacteria, such as B. thaliana, and encapsulated delta-endotoxins of B. thaliana prepared by the CellCap® process, such as MVP® and MVPII® Bioinsecticides (CellCap ® , MVP ® and MVPII ® are trademarks of Mycogen Corporation, Indianapolis, Indiana, USA); entomopathogenic fungi such as Metarhizium anisopliae fungus (green muscardine fungus); and entomopathogenic (naturally occurring and genetically modified) viruses, including baculoviruses, nuclear polyhedrosis viruses (NPV), such as Helicoverpa zea nucleopolyhedrosis virus (HzNPV), celery nightworm Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granular viruses (GV) such as Cydia pomonella granulosis virus (CpGV).
用於與本揭露之化合物混合的生物劑的一個實施方式包括以下中的一個或組合：(i) 放線菌（ Actinomycetes）屬、農桿菌（ Agrobacterium）屬、節桿菌（ Arthrobacter）屬、產鹼桿菌（Alcaligenes）屬、金桿菌（Aureobacterium）屬、固氮菌（Azobacter）屬、桿菌（Bacillus）屬、拜葉林克氏菌（Beijerinckia）屬、慢生根瘤菌（Bradyrhizobium）屬、短芽孢桿菌（Brevibacillus）屬、伯克霍爾德（Burkholderia）屬、色桿菌（Chromobacterium）屬、梭菌（Clostridium）屬、棍狀桿菌（Clavibacter）屬、叢毛單胞菌（Comamonas）屬、棒狀桿菌（Corynebacterium）屬、短小桿菌（Curtobacterium）屬、腸桿菌（Enterobacter）屬、黃桿菌（Flavobacterium）屬、葡萄糖酸桿菌（Gluconobacter）屬、氫噬胞菌（Hydrogenophaga）屬、克雷伯氏菌（Klebsiella）屬、甲基桿菌（Methylobacterium）屬、類芽孢桿菌（Paenibacillus）屬、巴斯德氏菌（Pasteuria）屬、發光桿菌（Photorhabdus）屬、葉桿菌（Phyllobacterium）屬、假單胞菌（Pseudomonas）屬、根瘤菌（Rhizobium）屬、沙雷氏菌（Serratia）屬、鞘胺醇桿菌（Sphingobacterium）屬、寡養單胞菌（Stenotrophomonas）屬、鏈黴菌（Streptomyces）屬、貪噬菌（Variovorax）屬或致病桿菌（Xenorhabdus）屬細菌，例如解澱粉芽孢桿菌（Bacillus amyloliquefaciens）、蠟樣芽孢桿菌（Bacillus cereus）、堅強芽孢桿菌（Bacillus firmus）、地衣芽孢桿菌（Bacillus licheniformis）、短小芽孢桿菌（Bacillus pumilus）、球形芽孢桿菌（Bacillus sphaericus）、枯草芽孢桿菌（Bacillus subtilis）、蘇力菌、大豆慢生根瘤菌（Bradyrhizobium japonicum）、活性紫色細菌（Chromobacterium subtsugae）、凱撒巴斯德氏菌（Pasteuria nishizawae）、穿刺巴斯德氏菌（Pasteuria penetrans）、有用巴斯德氏菌（Pasteuria usage）、螢光假單胞菌（Pseudomonas fluorescens）和利迪鏈黴菌（Streptomyces lydicus）細菌；(ii) 真菌，諸如綠僵菌；(iii) 病毒，包括桿狀病毒、核多角體病毒，諸如穀實夜蛾核多角體病毒、芹菜夜蛾核多角體病毒；顆粒體病毒，諸如蘋果蠹蛾顆粒體病毒。 One embodiment of a biological agent for mixing with a compound of the present disclosure includes one or a combination of: (i) Actinomycetes , Agrobacterium , Arthrobacter , Alcaligenes (Alcaligenes), Aureobacterium, Azobacter, Bacillus, Beijerinckia, Bradyrhizobium, Brevibacillus ), Burkholderia, Chromobacterium, Clostridium, Clavibacter, Comamonas, Corynebacterium ), Curtobacterium, Enterobacter, Flavobacterium, Gluconobacter, Hydrogenophaga, Klebsiella , Methylobacterium, Paenibacillus, Pasteuria, Photorhabdus, Phyllobacterium, Pseudomonas, Rhizobium, Serratia, Sphingobacterium, Stenotrophomonas, Streptomyces, Variovorax or Bacteria of the genus Xenorhabdus, such as Bacillus amyloliquefaciens, Bacillus cereus, Bacillus firmus, Bacillus licheniformis, Bacillus pumilus ), Bacillus sphaericus, Bacillus subtilis, Thule, Bradyrhizobium japonicum, Chromoba cterium subtsugae), Pasteuria nishizawae, Pasteuria penetrans, Pasteuria usage, Pseudomonas fluorescens and Liddy Streptomyces lydicus bacteria; (ii) fungi, such as Metarhizium anisopliae; (iii) viruses, including baculoviruses, nucleopolyhedrosis viruses, such as Helicoptera lydicus nucleopolyhedrosis virus, Spodoptera erythra nucleopolyhedrosis virus ; Granular viruses, such as codling moth granular virus.
特別值得注意的是其中另一無脊椎害蟲防治活性成分屬於與式 1的化合物不同的化學類別或具有與式 1的化合物不同的作用位點的這種組合。在某些情況下，與至少一種具有相似防治譜但是不同作用位點的其他無脊椎害蟲防治活性成分的組合對於抗性管理將是特別有利的。因此，本揭露之組成物可以進一步包含生物學有效量的至少一種附加無脊椎害蟲防治活性成分，該活性成分具有相似的防治譜但是屬於不同的化學類別或具有不同的作用位點。該等附加生物學活性化合物或藥劑包括但不限於乙醯膽鹼酯酶（AChE）抑制劑，諸如胺基甲酸酯類滅多威、殺線威、硫雙威、唑蚜威以及有機磷類毒死蜱；GABA門控氯離子通道拮抗劑，諸如環二烯類狄氏劑和硫丹，以及苯吡唑類乙蟲腈和氟蟲腈；鈉通道調節劑，諸如擬除蟲菊酯類聯苯菊酯、氟氯氰菊酯、高效氟氯氰菊、三氟氯氰菊酯、高效三氟氯氰菊酯、氯氰菊酯、溴氰菊酯、四氟甲醚菊酯、高氰戊菊酯、甲氧苄氟菊酯和丙氟菊酯；菸鹼型乙醯膽鹼受體（nAChR）促効劑，諸如新菸鹼類啶蟲脒、噻蟲胺、呋蟲胺、吡蟲啉、烯啶蟲胺、硝蟲噻𠯤、噻蟲啉和噻蟲𠯤、及氟啶蟲胺腈；菸鹼型乙醯膽鹼受體（nAChR）變構活化劑，諸如多殺菌素類（spinosyns）乙基多殺菌素和多殺菌素；氯通道活化劑，諸如阿維菌素、阿巴汀和甲胺基阿維菌素；保幼激素類似物（juvenile hormone mimics），諸如苯蟲醚、烯蟲酯、苯氧威和吡丙醚；選擇性同翅目進食阻斷劑，諸如吡蚜酮和氟啶蟲醯胺；蟎蟲生長抑制劑，諸如乙蟎唑；粒線體ATP合成酶抑制劑，諸如炔蟎特；經由破壞質子梯度的氧化磷酸化的解偶合劑，諸如溴蟲腈；菸鹼型乙醯膽鹼受體（nAChR）通道阻斷劑，諸如沙蠶毒素類似物（nereistoxin analog）殺螟丹；甲殼素生物合成抑制劑，諸如苯甲醯脲類氟蟲脲、氟鈴脲、虱蟎脲、氟醯脲、多氟脲和殺鈴脲以及噻𠯤酮；雙翅目蛻皮干擾劑（moulting disrupter），諸如滅蠅胺；蛻皮激素受體促効劑，諸如二芳甲醯基肼類甲氧蟲醯肼和蟲醯肼；章魚胺受體促効劑，諸如雙甲脒；粒線體複合物III電子傳輸抑制劑，諸如氟蟻腙；粒線體複合物I電子傳輸抑制劑，諸如噠蟎靈；電壓依賴性鈉通道阻斷劑，諸如茚蟲威；乙醯輔酶A羧化酶抑制劑，諸如季酮酸類和特特拉姆酸類（tetramic acids）螺蟎酯、螺甲蟎酯和螺蟲乙酯；粒線體複合物II電子傳輸抑制劑，諸如β-酮腈類腈吡蟎酯和丁氟蟎酯；蘭尼鹼受體調節劑，諸如胺茴酸二醯胺（anthranilic diamides）氯蟲苯甲醯胺、溴氰蟲醯胺和溴氰蟲醯胺，二醯胺類，諸如氟蟲二醯胺，以及蘭尼鹼受體配位基，諸如蘭尼鹼；其中負責生物學活性的靶位點未知或未表徵的化合物，諸如印楝素、聯苯肼酯、啶蟲丙醚、吡氟喹蟲唑和三氟苯嘧啶；昆蟲中腸膜的微生物干擾劑，諸如蘇力菌及其產生的δ-內毒素以及球形芽孢桿菌；以及生物製劑，包括核多角體病毒（NPV）和其他天然存在的或經遺傳修飾的殺昆蟲病毒。 Of particular note are such combinations wherein the other invertebrate pest control active ingredient belongs to a different chemical class or has a different site of action than the compound of Formula 1 . Combination with at least one other invertebrate pest control active ingredient having a similar control spectrum but a different site of action will be particularly advantageous for resistance management in certain cases. Accordingly, the compositions of the present disclosure may further comprise a biologically effective amount of at least one additional invertebrate pest control active ingredient having a similar control spectrum but belonging to a different chemical class or having a different site of action. Such additional biologically active compounds or agents include, but are not limited to, acetylcholinesterase (AChE) inhibitors such as the carbamates methomyl, methomyl, thiodicarb, thiamicarb, and the organophosphate chlorpyrifos ; GABA-gated chloride channel antagonists, such as the cyclodienes dieldrin and endosulfan, and the phenylpyrazoles ethiprole and fipronil; sodium channel modulators, such as the pyrethroids bifenthrin beta-cyhalothrin, cyfluthrin, lambda-cyhalothrin, cyhalothrin, beta-cyhalothrin, cypermethrin, deltamethrin, perfluthrin, esfenvalerate, metofluthrin and profluthrin Esters; nicotinic acetylcholine receptor (nAChR) agonists such as the neonicotinoids acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiazoprid, thiacloprid and clothianidin, and sulfoxaflor; nicotinic acetylcholine receptor (nAChR) allosteric activators such as spinosyns (spinosyns) spinosyn and spinosyn; chloride channel activation agents, such as abamectin, abatine, and emamectin; juvenile hormone mimics, such as aphenoxyfen, methoprene, fenoxycarb, and pyriproxyfen; selective Homopteran feeding blockers, such as pymetrozine and flunicamid; mite growth inhibitors, such as etoxazole; mitochondrial ATP synthase inhibitors, such as propargid; oxidized phosphoric acid via disruption of the proton gradient decouplers such as chlorfenapyr; nicotinic acetylcholine receptor (nAChR) channel blockers such as nereistoxin analogs (nereistoxin analog) cartap; chitin biosynthesis inhibitors such as Benzoylureas Fluflubenuron, hexaflumuron, lufenuron, flufenuron, polyfluxuron, and thiflumuron, and thiazoxone; dipteran moulting disruptors such as cyromazine; moulting Hormone receptor agonists, such as the diarylhydrazines methoxyfluzide and tebufenyl; octopamine receptor agonists, such as amitraz; mitochondrial complex III electron transport inhibitors, such as Hydrazone; mitochondrial complex I electron transport inhibitors, such as pyridaben; voltage-dependent sodium channel blockers, such as indoxacarb; acetyl-CoA carboxylase inhibitors, such as tetronic acids and tetronic acids Tetramic acids (tetramic acids) spirodiclofen, spirofen and spirotetramat; mitochondrial complex II electron transport inhibitors such as β-ketonitriles pyrifen and cyflufen; Nitrin receptor modulators, such as anthranilic diamides, chlorantraniliprole, cyantraniliprole, and cyantraniliprole, diamides, such as sulfluramid, and ryanodine receptor ligands, such as ryanodine; compounds in which the target site responsible for the biological activity is unknown or uncharacterized, such as azadirachtin, bifenazate, pyridalipr, pyrifluquinazole and trifluopyrim; microbial disruptors of insect midgut membranes, such as Bacillus thaliana and its delta-endotoxin produced, and Bacillus sphaericus; and biological agents, including nuclear polyhedrosis virus (N PV) and other naturally occurring or genetically modified insecticidal viruses.
可與本揭露化合物一起配製的生物學活性化合物或藥劑的其他實例係：殺真菌劑，諸如苯并噻二唑、二甲基𠰌啉、唑嘧菌胺、aminopyrifen、吲唑磺菌胺、敵菌靈、阿紮康唑、嘧菌酯、苯霜靈（benalaxyl，包括精苯霜靈（benalaxyl-M））、麥鏽靈、苯菌靈、苯噻菌胺（benthiavalicarb，包括苯噻菌胺（benthiavalicarb-isopropyl）、苯并烯氟菌唑、bethoxazin、樂殺蟎、聯苯、聯苯三唑醇、聯苯吡菌胺、滅瘟素（blasticidin-S）、啶醯菌胺（boscalid）、糠菌唑、乙嘧酚磺酸酯（bupirimate）、丁硫啶、萎鏽靈、環丙醯亞胺、敵菌丹、克菌丹、多菌靈、地茂散（chloroneb）、百菌清、乙菌利（chlozolinate）、氫氧化銅、王銅、硫酸銅、丁香菌酯、賽座滅（cyazofamid）、環氟菌胺、霜脲氰、環唑醇、嘧菌環胺、dichlobentiazox、抑菌靈、雙氯氰菌胺（diclocymet）、噠菌酮（diclomezine）、氯硝胺（dicloran）、乙黴威（diethofencarb）、苯醚甲環唑、氟嘧菌胺（diflumetorim）、甲菌定（dimethirimol）、烯醯𠰌啉、醚菌胺、烯唑醇（diniconazole，包括高效烯唑醇（diniconazole-M））、敵蟎普、dipymetitrone、二噻農（dithianon）、二噻茂烷、十二環𠰌啉、多果定、益康唑、乙環唑、克瘟散、烯肟菌酯（enoxastrobin，也稱為烯肟菌酯（enestroburin））、氟環唑、噻唑菌胺（ethaboxam）、乙菌定（ethirimol）、土菌靈（etridiazole）、㗁唑菌酮、咪唑菌酮（fenamidone）、烯肟菌胺、氯苯嘧啶醇、腈苯唑、甲呋醯胺、環醯菌胺（fenhexamide）、稻瘟醯胺（fenoxanil）、拌種咯、苯吡克咪徳（fenpicoxamid）、苯鏽啶（fenpropidine）、丁苯𠰌啉、胺苯吡菌酮、三苯基乙酸錫、三苯基氫氧化錫、福美鐵、嘧菌腙（ferimzone）、氟麥托醌、florylpicoxamid、氟醚菌醯胺、氟啶胺（fluazinam）、氟苯醚醯胺（flubeneteram）、咯菌腈、氟菌蟎酯、fluindapyr、氟𠰌啉、氟吡菌胺（fluopicolide）、氟吡菌醯胺、fluoxapiprolin、氟嘧菌酯、氟喹唑、氟矽唑、磺菌胺（flusulfamide）、氟噻唑菌腈、氟醯胺（flutolanil）、粉唑醇、氟唑菌醯胺、滅菌丹、稻瘟酞（fthalide，也稱為苯酞（phthalide）、麥穗寧、呋霜靈（furalaxyl）、呋吡菌胺、己唑醇、土菌消（hymexazole）、雙胍辛鹽（guazatine）、抑黴唑、亞胺唑、烷苯磺酸鹽（iminoctadine albesilate）、雙胍辛胺乙酸鹽（iminoctadine triacetate）、inpyrfluxam、硫雙威、種菌唑、ipfentrifluconazole、ipflufenoquin、異丙噻菌胺、異稻瘟淨（iprobenfos）、異菌脲、丙森鋅、isoflucypram、稻瘟靈（isoprothiolane）、吡唑萘菌胺（isopyrazam）、異噻菌胺、春雷黴素、醚菌酯、lancotrione、代森錳鋅、雙炔醯菌胺（mandipropamid）、曼德斯賓（mandestrobin）、代森錳、mapanipyrin、氯氟醚菌唑、滅鏽胺、消蟎多（meptyldinocap）、甲霜靈（包括高效甲霜靈（metalaxyl-M）/精甲霜靈（mefenoxam））、葉菌唑、磺菌威（methasulfocarb）、代森聯、苯氧菌胺、metyltetraprole、苯菌酮、腈菌唑、萘替芬（naftitine）、甲胂鐵銨（甲基胂酸鐵（ferric methanearsonate））、氟苯嘧啶醇、辛噻酮、呋醯胺、肟醚菌胺、惡霜靈（oxadixyl）、噻哌菌靈（oxathiapiprolin）、奧索利酸、㗁咪唑（oxpoconazole）、氧化萎鏽靈、土黴素、戊菌唑、戊菌隆（pencycuron）、氟唑菌苯胺、吡噻菌胺（penthiopyrad）、稻痕酯（perfurazoate）、亞磷酸（包括其鹽，例如，乙磷鋁（fosetyl-aluminm））、啶氧菌酯、哌丙靈（piperalin）、多氧黴素（polyoxin）、噻菌靈、咪鮮胺、腐黴利（procymidone）、霜黴威（propamocarb）、丙環唑、甲基代森鋅、碘喹唑酮（proquinazid）、硫菌威（prothiocarb）、丙硫菌唑、氟唑菌醯羥胺（Adepidyn®）、唑菌胺酯、唑胺菌酯、pyrapropoyne、唑菌酯、pyraziflumid、吡菌磷、吡菌苯威、pyributacarb、pyridachlometyl、啶斑肟（pyrifenox）、苯啶菌酮（pyriofenone）、perisoxazole、嘧黴胺（pyrimethanil）、啶斑肟、硝吡咯菌素（pyrrolnitrin）、咯喹酮（pyroquilon）、氟喹唑、滅蟎猛（quinmethionate）、quinofumelin、喹氧靈、五氯硝基苯、矽噻菌胺（silthiofam）、氟唑環菌胺（sedaxane）、矽氟唑（simeconazole）、螺環菌胺、鏈黴素、硫、戊唑醇、異丁乙氧喹啉、teclofthalam、葉枯酞、四氯硝基苯、特比萘芬、氟醚唑、噻苯達唑、噻呋醯胺、托布津、甲基托布津、塞侖、噻醯菌胺、甲基立枯磷、三氟甲氧威（tolprocarb）、甲苯氟磺胺、三唑酮、三唑醇、嘧菌醇、咪唑𠯤（triazoxide）、鹼式硫酸銅（tribasic copper sulfate）、氯啶菌酯、十三𠰌啉、肟菌酯、氟菌唑、三莫嘧三環唑（trimoprhamide tricyclazole）、肟菌酯、𠯤胺靈、滅菌唑、烯效唑（uniconazole）、有效黴素、纈菌胺（valifenalate，也稱為纈菌胺（valifenal））、乙烯菌核利（vinclozoline）、代森鋅、福美鋅、苯醯菌胺（zoxamide）和1-[4-[4-[5-(2,6-二氟苯基)-4,5-二氫-3-異㗁唑基]-2-噻唑基]-1-哌啶基]-2-[5-甲基-3-(三氟甲基)-1 H-吡唑-1-基]乙酮；殺線蟲劑，諸如氟吡菌醯胺、螺蟲乙酯、硫雙威、噻唑膦、阿巴汀、異菌脲、聯氟碸、二甲基二硫化物、噻唑沙芬、1,3-二氯丙烯（1,3-D）、威百畝（鈉和鉀）、棉隆、氯化苦、苯線磷（fenamiphos）、滅線磷、硫線磷（cadusaphos）、特丁硫磷、咪唑環磷（imicyafos）、殺線威、克百威、tioxazafen、堅強芽孢桿菌和凱撒巴斯德氏菌；殺菌劑，諸如鏈黴素；殺蟎劑，諸如雙甲脒、滅蟎猛、乙酯殺蟎醇、三環錫（cyhexatin）、三氯殺蟎醇、除蟎靈、乙蟎唑、喹蟎醚、苯丁錫、甲氰菊酯、唑蟎酯、噻蟎酮、克蟎特、噠蟎靈和吡蟎胺。 Other examples of biologically active compounds or agents that may be formulated with the compounds of the present disclosure are: fungicides such as benzothiadiazoles, dimethylsulphine, pyramethazone, aminopyrifen, indazolesulfin, dimethoxam Bactendazim, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M), micazolin, benomyl, benthiavalicarb (including benalaxyl (benthiavalicarb-isopropyl), benzovinfluconazole, bethoxazin, Lexa, biphenyl, bifentriazole, bixafen, blasticidin-S, boscalid , furfurazole, pyrimethrin sulfonate (bupirimate), buthiridine, wiltion, cyclopropanimide, captafol, captan, carbendazim, chloroneb, chlorothalon Qing, Chlozolinate, Copper Hydroxide, Copper King, Copper Sulfate, Syringstrobin, Cyazofamid, Cyflufenamide, Cymoxanil, Cycloconazole, Cyprodinil, Dichlobentiazox, Difenazol, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, Dimethirimol, dimethirimol, krasastrobin, diniconazole (including diniconazole-M), dimethirimol, dipymetitrone, dithianon, dithianoxane, Dodecycline, Dodine, Econazole, Etoconazole, Kemensan, Enoxastrobin (also known as Enestroburin), Econazole, Ethaboxam ), ethirimol, etridiazole, fenamidone, fenamidone, enoxastrobin, chlorpyrimidol, carbendazole, methiramide, cyclamate Amine (fenhexamide), rice blastamide (fenoxanil), seed dressing, fenpicoxamid (fenpicoxamid), fenpropidine (fenpropidine), butadiene, fenoxanil, triphenyltin acetate, Triphenyltin hydroxide, ferbam, ferrimzone (ferimzone), flumethorquinone, florylpicoxamid, fluoxetinamide, fluazinam, flubeneteram, fludioxonil, Fluprofen, fluindapyr, fluopicoline, fluopicolide, fluopicolide Amine, fluoxapiprolin, fluoxastrobin, fluquinazole, flusilazole, flusulfamide, fluthiazolin, flutolanil, fuconazole, flucloxam, folpet, rice Fthalide (also known as phthalide, wheat suingin, furalaxyl, furamet, hexaconazole, hymexazole, biguanide octyl salt (guazatine), antifungal Azole, iminoxazole, iminoctadine albesilate, iminoctadine triacetate, inpyrfluxam, thiodicarb, bacconazole, ipfentrifluconazole, ipflufenoquin, iprothicarb, isopyrflux ( iprobenfos), iprodione, zinc, isoflucypram, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, lancotrione, mancozeb, bis Mandipropamid, mandestrobin, maneb, mapanipyrin, chlorofluconazole, propazam, meptyldinocap, metalaxyl (including metalaxyl -M)/mefenoxam), metconazole, methasulfocarb, methasulfone, fenoxystrobin, metyltetraprole, mefenone, myclobutanil, naftitine, Ferric ammonium arsenate (ferric methanearsonate), flumecilidine, octhilone, furamide, oryzastrobin, oxadixyl, oxathiapiprolin, Solic acid, oxpoconazole, oxidized carboxyl, oxytetracycline, penconazole, pencycuron, flufenadine, penthiopyrad, perfurazoate, Phosphorous acid (including its salts, eg, fosetyl-aluminm), picoxystrobin, piperalin, polyoxin, thiabendazole, prochloraz, procymidone (procymidone), propamocarb, propiconazole, zinc-methyl, iodoquinazolone (proquinazid), thiocarb (prothiocarb), prothioconazole, flucloxacin (Adepidyn®) , pyraclostrobin, pyraclostrobin, pyrapropoyne , pyraclostrobin, pyraziflumid, pyrafos, pyribencarb, pyributacarb, pyridachlometyl, pyrifenox, pyriofenone, perisoxazole, pyrimethanil, pyridoxine, nitropyrrole Pyrrolnitrin, pyroquilon, fluquinazole, quinmethionate, quinofumelin, quinoxyphen, pentachloronitrobenzene, silthiofam, fluxazone ( sedaxane), simeconazole, spirulina, streptomycin, sulfur, tebuconazole, ibuethoxyquinoline, teclofthalam, tecloftalm, tetrachloronitrobenzene, terbinafine, fluoride Epoxazole, thiabendazole, thiafuramide, thiophanate, thiophanate-methyl, thiaren, thiazamide, tolclofos-methyl, tolprocarb, tolflusulfonamide, triazole Ketone, Triadimenol, Azoxystrobin, Triazoxide, Tribasic Copper Sulfate, Chloroprexate, Tridetrizoline, Trifloxystrobin, Fluclopyr, Tricyclazole (trimoprhamide tricyclazole), trifloxystrobin, tricyclazole, fenconazole, uniconazole, validamycin, valifenalate (also known as valifenal), vinclozoline ), Zinc, Zoxam, Zoxamide and 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-iso㗁Azolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl) -1H -pyrazol-1-yl]ethanone; nematicide , such as fluopyram, spirotetramat, thiodicarb, thiazophos, abatine, iprodione, bifluridine, dimethyl disulfide, thiazoxafin, 1,3-dichloropropene (1,3-D), metabam (sodium and potassium), dacememe, chloropicrin, fenamiphos, fenamiphos, cadusaphos, terbufos, imidazocycline (imicyafos), oxacarb, carbofuran, tioxazafen, Bacillus firmus, and Pasteurella ceesar; fungicides, such as streptomycin; acaricides, such as amitraz, acefuran, ethyl ester acaricide Alcohol, cyhexatin, dicofol, fenpyr, etoxazole, fenazaquin, fenbutatin, fenpropathrin, fenpyroximate, hexyzafen, clofenac, pyridaben, and pyridaben amine.
在某些情況下，本揭露之化合物與其他生物學活性（特別是無脊椎害蟲防治）化合物或藥劑（即活性成分）的組合可導致增強的效應。降低釋放在環境中的活性成分的量，同時確保有效的害蟲防治一直係人們所期望的。當增強的無脊椎害蟲防治以獲得農學上令人滿意的無脊椎害蟲防治水平的施加量出現時，此類組合可有利地用於降低作物生產成本並且減少環境負荷。In certain instances, combinations of compounds of the present disclosure with other biologically active (particularly invertebrate pest control) compounds or agents (ie, active ingredients) may result in enhanced effects. It would be desirable to reduce the amount of active ingredient released in the environment while ensuring effective pest control. Such combinations can be advantageously used to reduce crop production costs and reduce environmental load when enhanced invertebrate pest control is present at application rates to achieve agronomically satisfactory levels of invertebrate pest control.
可以將本揭露之化合物及其組成物施加於經遺傳轉化以表現對無脊椎害蟲有毒的蛋白質（諸如蘇力菌δ-內毒素）的植物。此種施加可提供更廣譜的植物保護，並且對於抗性管理係有利的。本揭露之外源性施加的無脊椎害蟲防治化合物與表現的毒素蛋白質組合可提供增強的效應。Compounds of the present disclosure and compositions thereof can be applied to plants genetically transformed to express proteins that are toxic to invertebrate pests, such as B. thuringiensis delta-endotoxin. Such application can provide broader spectrum plant protection and is advantageous for resistance management lines. Combinations of exogenously applied invertebrate pest control compounds and expressed toxin proteins of the present disclosure can provide enhanced effects.
該等農用保護劑（即殺昆蟲劑、殺真菌劑、殺線蟲劑、殺蟎劑、除草劑和生物劑）的一般參考文獻包括 The Pesticide Manual[農藥手冊], 第13版, C.D. S. Tomlin編輯, British Crop Protection Council [英國作物保護委員會], Farnham, Surrey, U.K. [英國薩里法納姆], 2003和 The BioPesticide Manual[生物農藥手冊], 第 2 版, L. G. Copping編輯,英國作物保護委員會, 英國薩里法納姆, 2001。 General references to such agricultural protective agents (i.e., insecticides, fungicides, nematicides, acaricides, herbicides, and biological agents) include The Pesticide Manual , 13th edition, edited by CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2003 and The BioPesticide Manual , 2nd Edition , edited by LG Copping, UK Crop Protection Council , UK Surrey Farnham, 2001.
本揭露之化合物可與多核苷酸組合或一起配製，該等多核苷酸包括但不限於DNA、RNA和/或化學修飾的核苷酸，該等核苷酸藉由減量調節、干擾、抑制或緘默呈現殺昆蟲效果的遺傳衍生的轉錄物來影響特定靶的量。Compounds of the present disclosure may be combined or formulated with polynucleotides including, but not limited to, DNA, RNA, and/or chemically modified nucleotides that are modified by downregulation, interference, inhibition, or Silencing exhibits insecticidal effects on the amount of genetically derived transcripts to affect specific targets.
對於其中使用該等不同混合組分中的一種或多種的實施方式，該等不同混合組分（總量）與式 1的化合物的重量比典型地在約1:3000與約3000:1之間。值得注意的是在約1:300與約300:1之間的重量比（例如在約1:30與約30:1之間的比率）。熟悉該項技術者可以藉由簡單的實驗容易地確定期望的生物活性譜所必需的活性成分的生物有效量。將明顯的是，包含該等附加組分可使無脊椎害蟲防治譜擴展超出由單獨的式 1的化合物的防治譜。 For embodiments wherein one or more of the different mixing components are used, the weight ratio of the different mixing components (in total) to the compound of Formula 1 is typically between about 1:3000 and about 3000:1 . Of note are weight ratios between about 1:300 and about 300:1 (eg, ratios between about 1:30 and about 30:1). A person skilled in the art can readily determine by simple experimentation the biologically effective amount of the active ingredient necessary for the desired profile of biological activity. It will be apparent that inclusion of such additional components extends the spectrum of invertebrate pest control beyond that achieved by the compound of Formula 1 alone.
在農學和非農學應用中，藉由將生物學有效量的一種或多種典型地呈組成物形式的本揭露之化合物施加到害蟲環境，包括侵害的農學和/或非農學所在地，施加到待保護的區域，或直接施加到待防治的害蟲，來防治無脊椎害蟲。In agronomic and non-agronomic applications, by applying a biologically effective amount of one or more compounds of the present disclosure, typically in composition form, to the pest environment, including the agronomic and/or non-agronomic locus of infestation, the for the control of invertebrate pests, or by applying directly to the pest to be controlled.
因此，本揭露包括一種用於在農學和/或非農業應用中防治無脊椎害蟲之方法，該方法包括使無脊椎害蟲或其環境與生物學有效量的一種或多種本揭露之化合物或與包含至少一種這樣的化合物的組成物或包含至少一種這樣的化合物和生物學有效量的至少一種附加生物學活性化合物或藥劑的組成物接觸。包含本揭露之化合物和生物學有效量的至少一種附加生物學活性化合物或藥劑的合適組成物的實例包括顆粒狀組成物，其中該附加活性化合物存在於與本揭露之化合物相同的顆粒劑上或存在於與本揭露之化合物的那些顆粒劑分開的顆粒劑上。Accordingly, the present disclosure includes a method for controlling invertebrate pests in agronomic and/or non-agricultural applications, the method comprising administering to the invertebrate pest or an environmentally and biologically effective amount thereof one or more compounds of the present disclosure or in combination with A composition of at least one such compound or a composition comprising at least one such compound is contacted with a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the present disclosure and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions wherein the additional active compound is present on the same granule as the compound of the present disclosure or present on granules separate from those of the compounds of the present disclosure.
為實現與本揭露之化合物或組成物接觸以保護大田作物免受無脊椎害蟲的侵害，典型地在種植之前將該化合物或組成物施加到作物種子，施加到作物植株的葉子（例如，葉、莖、花、果實），或在種植作物之前或之後施加到土壤或其他生長介質。To effect protection of field crops from invertebrate pests in contact with a compound or composition of the present disclosure, the compound or composition is typically applied to the crop seeds, to the foliage (e.g., leaves, stems, flowers, fruits), or applied to soil or other growing media before or after planting the crop.
接觸方法的一個實施方式係藉由噴霧。替代性地，包含本揭露之化合物的顆粒狀組成物可以施加到植物葉子或土壤。也可以藉由使植株與作為液體製劑的土壤浸液、到土壤中的顆粒狀製劑、育苗箱處理物或移植浸漬液施加的包含本揭露之化合物的組成物接觸來藉由植物吸收有效地遞送本揭露之化合物。值得注意的是呈土壤浸液液體製劑形式的本揭露之組成物。還值得注意的是用於防治無脊椎害蟲之方法，該方法包括使無脊椎害蟲或其環境與生物學有效量的本揭露之化合物或與包含生物學有效量的本揭露之化合物的組成物接觸。進一步值得注意的是這種方法，其中環境係土壤並且組成物作為土壤浸液製劑施加到土壤。進一步值得注意的是本揭露之化合物藉由局部施加到侵害的所在地也是有效的。其他接觸方法包括藉由直接噴霧和滯留噴霧、空氣噴霧、凝膠、種子包衣、微膠囊化、內吸吸收、誘餌、耳標、大丸藥、噴霧器、熏劑、氣溶膠、粉劑以及許多其他方法來施加本揭露之化合物或組成物。接觸方法的一個實施方式係包含本揭露之化合物或組成物的尺寸上穩定的肥料顆粒劑、棒或片劑。本揭露之化合物還可浸漬到用於製造無脊椎害蟲防治裝置（例如，防昆蟲網）的材料中。One embodiment of the contacting method is by spraying. Alternatively, granular compositions comprising compounds of the present disclosure may be applied to plant foliage or soil. Effective delivery by plant uptake may also be achieved by contacting the plant with a composition comprising a compound of the present disclosure applied as a liquid formulation as a soil drench, a granular formulation into the soil, a nursery box treatment, or a transplant dip. Compounds of the present disclosure. Of note are the compositions of the present disclosure in the form of soil drench liquid formulations. Also of note are methods for controlling invertebrate pests comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of the present disclosure or with a composition comprising a biologically effective amount of a compound of the present disclosure . Of further note is the method wherein the environment is the soil and the composition is applied to the soil as a soil drench formulation. It is further worth noting that the compounds of the present disclosure are also effective by topical application to the locus of infestation. Other methods of exposure include via direct and residual sprays, air sprays, gels, seed coatings, microencapsulation, systemic absorption, baits, ear tags, boluses, nebulizers, fumigants, aerosols, powders, and many others Methods to apply the compounds or compositions of the present disclosure. One embodiment of the contacting method is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the present disclosure. The compounds of the present disclosure may also be impregnated into materials used in the manufacture of invertebrate pest control devices such as insect nets.
本揭露之化合物可用於處理所有植株、植株部分和種子。植株和種子品種和栽培品系可藉由常規的繁殖和育種方法或藉由遺傳工程方法獲得。經遺傳修飾的植株或種子（轉基因植物或種子）係其中異源性基因（轉基因）已被穩定整合進植株或種子基因組中的那些。由轉基因在植株基因組中的特定位置所限定的轉基因被稱為轉化或轉基因事件。The compounds of the present disclosure can be used to treat all plants, plant parts and seeds. Plant and seed varieties and cultivars can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a heterologous gene (transgene) has been stably integrated into the genome of the plant or seed. A transgene defined by a specific position of the transgene in the plant genome is called a transformation or transgenic event.
可根據本揭露處理的經遺傳修飾的植株和種子栽培品系包括抵抗一種或多種生物脅迫（害蟲，諸如線蟲、昆蟲、蟎蟲、真菌等）或非生物脅迫（乾旱、低溫、土壤鹽化等）的那些栽培品系，或包含其他期望的特徵的那些栽培品系。植株和種子可經遺傳修飾以表現出以下性狀，例如除草劑耐受性、昆蟲抗性、改性的油特徵或耐旱性。包括單個基因轉化事件或轉化事件的組合的有用的經遺傳修飾的植株和種子列出於表Z中。對於表Z中列出的遺傳修飾的附加資訊可獲自以下資料庫： OECD BioTrack產品資料庫（OECD BioTrack Product Database）[線上資料庫]。使用互聯網＜https://biotrackproductdatabase.oecd.org/byidentifier.aspx＞從經濟合作與發展組織（OECD）檢索 美國農業部動植物衛生檢驗署（USDA Animal and Plant Health Inspection Service）[線上資料庫]。使用互聯網＜http://www.aphis.usda.gov＞從美國農業部（US Department of Agriculture）檢索 轉基因生物的有意釋放和向歐盟市場的投放-轉基因生物註冊（Deliberate Release and Placing on the EU Market of GMOs - GMO Register）[線上資料庫]。使用互聯網＜http://gmoinfo.jrc.ec.europa.eu＞從歐洲委員會聯合研究中心（European Commission Joint Research Centre）檢索 以下縮寫用於隨後的表Z中：tol.為耐受性，res.為抗性，SU為磺醯脲類，ALS為乙醯乳酸合酶，HPPD為4-羥基苯丙酮酸雙加氧酶，NA為不可用。 Genetically modified plants and seed cultivars that can be treated in accordance with the present disclosure include those resistant to one or more biotic stresses (pests such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, low temperature, soil salinization, etc.) Those cultivars, or those cultivars comprising other desirable characteristics. Plants and seeds can be genetically modified to exhibit traits such as herbicide tolerance, insect resistance, modified oil characteristics, or drought tolerance. Useful genetically modified plants and seeds comprising single gene transformation events or combinations of transformation events are listed in Table Z. Additional information for the genetic modifications listed in Table Z can be obtained from the following databases: OECD BioTrack Product Database [online database]. Retrieved from the Organization for Economic Co-operation and Development (OECD) using the Internet <https://biotrackproductdatabase.oecd.org/byidentifier.aspx> USDA Animal and Plant Health Inspection Service [online database]. Retrieved from the US Department of Agriculture using the Internet <http://www.aphis.usda.gov> Deliberate Release and Placing on the EU Market of GMOs - GMO Register [online database]. Retrieved from the European Commission Joint Research Center using the Internet <http://gmoinfo.jrc.ec.europa.eu> The following abbreviations are used in the following Table Z: tol. for tolerance, res. for resistance, SU for sulfonylureas, ALS for acetyl lactate synthase, HPPD for 4-hydroxyphenylpyruvate dioxygenase , NA means unavailable.
[表Z]
*阿根廷，**波蘭，#茄子*Argentina, **Poland, #eggplant
用本揭露之化合物處理經遺傳修飾的植株和種子可導致增強的效應。例如，降低施加量、拓展活性譜、增加對生物/非生物脅迫的耐受性或增強儲存穩定性可大於由在經遺傳修飾的植株和種子上施加本揭露之化合物的僅簡單加性效應所預期的。Treatment of genetically modified plants and seeds with compounds of the present disclosure results in enhanced effects. For example, reducing application rates, broadening the spectrum of activity, increasing tolerance to biotic/abiotic stresses, or enhancing storage stability may be greater than would be accounted for by a mere additive effect of applying the compounds of the present disclosure on genetically modified plants and seeds. expected.
本揭露之化合物還可用於種子處理中以保護種子免受無脊椎害蟲的侵害。在本揭露和申請專利範圍之上下文中，處理種子意指使種子與生物學有效量的典型地被配製成本揭露之組成物的本揭露之化合物接觸。這種種子處理保護種子免受無脊椎土壤害蟲的侵害並且總體上還可以保護由發芽種子發育成的幼苗的根和其他與土壤接觸的植株部分。種子處理還可以藉由使本揭露之化合物或第二活性成分在發育中的植株中易位來向葉子提供保護。可向所有類型的種子施加種子處理，包括將發芽形成遺傳轉化以表現特定性狀的植株的那些種子。代表性實例包括表現對無脊椎害蟲有毒的蛋白質的那些，諸如蘇力菌毒素，或表現抗除草劑性的那些，諸如提供草甘膦抗性的草甘膦乙醯轉移酶。使用本揭露之化合物的種子處理還可增加由經處理的種子生長出的植株的活力。The compounds of the present disclosure may also be used in seed treatments to protect seeds from invertebrate pests. In the context of the present disclosure and claims, treating a seed means contacting the seed with a biologically effective amount of a compound of the present disclosure, typically formulated into a composition of the disclosure. This seed treatment protects the seed from invertebrate soil pests and generally also protects the roots and other parts of the plant that come into contact with the soil of the seedlings developing from the germinated seeds. Seed treatments can also provide protection to foliage by translocating a compound of the present disclosure or a second active ingredient in the developing plant. Seed treatments can be applied to all types of seeds, including those that will germinate to form plants genetically transformed to exhibit a particular trait. Representative examples include those expressing proteins that are toxic to invertebrate pests, such as thurotoxin, or those that express herbicide resistance, such as glyphosate acetyltransferase that confers glyphosate resistance. Seed treatment with compounds of the present disclosure can also increase the vigor of plants grown from the treated seeds.
種子處理的一種方法係在播撒種子之前，藉由用本揭露之化合物（即作為配製的組成物）對種子進行噴霧或撒粉。經配製用於種子處理的組成物通常包含成膜劑或黏合劑。因此，典型地本揭露之種子包衣組成物包含生物學有效量的式 1的化合物、其 N-氧化物或鹽以及成膜劑或黏合劑。可藉由將可流動的懸浮液濃縮物直接噴霧到種子的翻滾床中並且然後乾燥種子來為種子包衣。替代性地，可將其他製劑類型諸如濕粉、溶液、懸浮乳液、可乳化的濃縮物和水中的乳液噴霧在種子上。該方法特別可用於將膜包衣施加在種子上。熟悉該項技術者可使用各種包衣及其和方法。合適之方法包括在P. Kosters等人， Seed Treatment: Progress and Prospects[種子處理：進展與前景], 1994 BCPC專著號57以及其中列出的參考文獻中列出的那些方法。 One method of seed treatment is by spraying or dusting the seeds with a compound of the present disclosure (ie, as a formulated composition) prior to sowing the seeds. Compositions formulated for seed treatment typically include film formers or binders. Therefore, typically the seed coating composition of the present disclosure comprises a biologically effective amount of a compound of formula 1 , its N -oxide or salt, and a film former or binder. Seeds can be coated by spraying the flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Alternatively, other formulation types such as wet powders, solutions, suspoemulsions, emulsifiable concentrates and emulsions in water can be sprayed onto the seeds. This method is particularly useful for applying film coatings to seeds. Various coatings and methods are available to those skilled in the art. Suitable methods include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects , 1994 BCPC Monograph No. 57 and references listed therein.
式 1的化合物和它們的組成物，單獨地或者與其他殺昆蟲劑和殺真菌劑組合，特別可用於對作物的種子處理，該等作物包括但不限於玉蜀黍或玉米、大豆、棉、穀類（例如，小麥、燕麥、大麥、黑麥和稻）、馬鈴薯、蔬菜和油菜。 Compounds of formula 1 and their compositions, alone or in combination with other insecticides and fungicides, are particularly useful for seed treatment of crops including, but not limited to, maize or corn, soybeans, cotton, cereals ( For example, wheat, oats, barley, rye and rice), potatoes, vegetables and canola.
可與式 1的化合物一起配製以提供可用於種子處理的混合物的其他殺昆蟲劑包括阿巴汀、啶蟲脒、氟丙菊酯、雙甲脒、阿維菌素、印楝素、殺蟲磺、聯苯菊酯、噻𠯤酮、甲萘威、克百威、殺螟丹、氯蟲苯甲醯胺、溴蟲腈、毒死蜱、噻蟲胺、溴氰蟲醯胺、氟氯氰菊酯、高效氟氯氰菊、三氟氯氰菊酯、精高效氯氟氰菊酯、高效氯氟氰菊酯、氯氰菊酯、順式氯氰菊酯、ζ-氯氰菊酯、滅蠅胺、溴氰菊酯、狄氏劑、呋蟲胺、苯蟲醚、甲胺基阿維菌素、硫丹、高氰戊菊酯、乙蟲腈、醚菊酯、乙蟎唑、苯硫威、苯氧威、氰戊菊酯、氟蟲腈、氟啶蟲醯胺、氟蟲雙醯胺、氟蟲脲、氟胺氰菊酯、伐蟲脒、噻唑膦、氟鈴脲、氟蟻腙、吡蟲啉、茚蟲威、虱蟎脲、氰氟蟲腙、甲硫威、滅多威、烯蟲酯、甲氧蟲醯肼、烯啶蟲胺、硝蟲噻𠯤、氟醯脲、殺線威、吡蚜酮、除蟲菊素、噠蟎靈、啶蟲丙醚、吡丙醚、蘭尼鹼、乙基多殺菌素、多殺菌素、螺蟎酯、螺甲蟎酯、螺蟲乙酯、氟啶蟲胺腈、蟲醯肼、胺菊酯、噻蟲啉、噻蟲𠯤、硫雙威、殺蟲雙、四溴菊酯、唑蚜威、殺鈴脲、蘇力菌δ-內毒素、蘇力菌的所有菌株和核多角體病毒的所有毒株。 Other insecticides that can be formulated with the compound of formula 1 to provide mixtures useful for seed treatment include abatine, acetamiprid, bifenthrin, amitraz, abamectin, azadirachtin, insecticide Sulfur, bifenthrin, thiophene, carbaryl, carbofuran, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyanantraniliprole, cyfluthrin, high-efficiency Cyfluthrin, cyhalothrin, fine-beta-cyhalothrin, lambda-cyhalothrin, cypermethrin, cis-cypermethrin, ζ-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran , diphenoxyfen, emamectin, endosulfan, esfenvalerate, ethiprole, etofenproxil, etoxazole, fenthiocarb, fenoxycarb, fenvalerate, fipronil , flunicamid, flubendiamide, flubenzuron, fluvalinate, fentamiprid, thiazophos, hexaflumuron, hydrazone, imidacloprid, indoxacarb, lufenuron, cyanofluoride Hydrazone, methylthiocarb, methomyl, methoprene, methoxyfluzate, nitenpyram, nitrepyrid, fluorocarburon, methoxycarb, pymetrozine, pyrethrins, pyridaben , acetamiprop, pyriproxyfen, ryanodine, spinosad, spinosad, spirodiclofen, spiromethimate, spirotetramat, sulfoxaflor, chlorhydrazine, chlorpyrifos Esters, thiacloprid, thiamethoxam, thiodicarb, dimehypo, perfenthrin, pyrabicarb, flufluron, thaliana delta-endotoxin, all strains of thaliana, and nuclear polyhedrosis virus of all strains.
可與式 1的化合物一起配製以提供可用於種子處理的混合物的殺真菌劑包括吲唑磺菌胺、嘧菌酯、啶醯菌胺、多菌靈、萎鏽靈、霜脲氰、環唑醇、苯醚甲環唑、烯醯𠰌啉、氟啶胺、咯菌腈、氟喹唑、氟吡菌胺、氟嘧菌酯、粉唑醇、氟唑菌醯胺、種菌唑、異菌脲、甲霜靈、精甲霜靈、葉菌唑、腈菌唑、多效唑、氟唑菌苯胺、啶氧菌酯、丙硫菌唑、唑菌胺酯、氟唑環菌胺、矽噻菌胺、戊唑醇、噻苯達唑、甲基托布津、塞侖、肟菌酯和滅菌唑。 Fungicides that can be formulated with the compound of Formula 1 to provide mixtures useful in seed treatment include indazolesulprobin, azoxystrobin, boscalid, carbendazim, carboxim, cymoxanil, cycloconazole Alcohol, Difenoconazole, Difenoconazole, Enyl, Fluazinamide, Fludioxonil, Fluquinazole, Fluopicolide, Fluoxastrobin, Fenconazole, Flufenpyramide, Buconazole, Isobacteria Urea, metalaxyl, refined metalaxyl, metconazole, myclobutanil, paclobutrazol, flufenadil, pyroxystrobin, prothioconazole, pyraclostrobin, flufenazol, silthiazol amines, tebuconazole, thiabendazole, thiophanate-methyl, thiram, trifloxystrobin, and fafenazole.
可用於種子處理的包含式 1的化合物的組成物可進一步包含細菌，諸如短小芽孢桿菌（例如，菌株GB34）和堅強芽孢桿菌（例如，分離物1582）、根瘤菌接種劑/增充劑、異黃酮和脂殼寡糖。 Compositions comprising a compound of formula 1 useful for seed treatment may further comprise bacteria such as Bacillus pumilus (for example, strain GB34) and Bacillus firmus (for example, isolate 1582), rhizobia inoculants/extenders, isobacteria Flavonoids and lipooligosaccharides.
經處理的種子典型地包含本揭露之化合物，其量係從約0.1 g至1 kg/100 kg種子（即按處理前該種子的重量計從約0.0001%至1%）。經配製用於種子處理的可流動的懸浮液典型地包含從約0.5%至約70%的活性成分、從約0.5%至約30%的成膜黏合劑、從約0.5%至約20%的分散劑、從0%至約5%的增稠劑、從0%至約5%的顏料和/或染料、從0%至約2%的消泡劑、從0%至約1%的防腐劑以及從0%至約75%的揮發性液體稀釋劑。Treated seeds typically comprise a compound of the present disclosure in an amount of from about 0.1 g to 1 kg per 100 kg of seed (ie, from about 0.0001% to 1% by weight of the seed prior to treatment). Flowable suspensions formulated for seed treatment typically contain from about 0.5% to about 70% active ingredient, from about 0.5% to about 30% film-forming binder, from about 0.5% to about 20% Dispersants, thickeners from 0% to about 5%, pigments and/or dyes from 0% to about 5%, defoamers from 0% to about 2%, corrosion inhibitors from 0% to about 1% and volatile liquid diluents from 0% to about 75%.
本揭露之化合物可摻入被無脊椎害蟲食用的餌料組成物中或用於諸如誘捕器、誘餌站等的裝置中。此種誘餌組成物可呈顆粒劑的形式，該顆粒劑包含 (a) 活性成分，即生物學有效量的式 1的化合物、其 N-氧化物或鹽；(b) 一種或多種食物材料；視需要 (c) 引誘劑，和視需要 (d) 一種或多種濕潤劑。值得注意的是顆粒劑或誘餌組成物，該等顆粒劑或誘餌組成物包含在約0.001%-5%之間的活性成分、約40%-99%之間的食物材料和/或引誘劑；以及視需要約0.05%-10%之間的濕潤劑，它們可在非常低的施加量下，特別是藉由攝取而不是藉由直接接觸時致死的活性成分劑量下，有效防治土壤無脊椎害蟲。一些食物材料可用作食物來源和引誘劑二者。食物材料包括碳水化合物、蛋白質和脂質。食物材料的實例係蔬菜粉、糖、澱粉、動物脂肪、植物油、酵母提取物和乳固體。引誘劑的實例係增味劑和風味劑，諸如水果或植物提取物、香料、或其他動物或植物組分、資訊素或已知用於吸引目標無脊椎害蟲的其他劑。濕潤劑（即保水劑）的實例係乙二醇和其他多元醇、甘油和山梨糖醇。值得注意的是用於防治至少一種選自由螞蟻、白蟻和蟑螂組成之群組的無脊椎害蟲的誘餌組成物（以及使用此種誘餌組成物之方法）。一種用於防治無脊椎害蟲的裝置可包含本發明之誘餌組成物和被適配成用於容納誘餌組成物的外殼，其中外殼具有至少一個開口，該開口的大小被設定成允許無脊椎害蟲通過開口，使無脊椎害蟲能夠從外殼外部的位置接近誘餌組成物，並且其中外殼進一步被適配成放置在無脊椎害蟲可能或已知的活動所在地中或附近。 The compounds of the present disclosure may be incorporated into bait compositions eaten by invertebrate pests or used in devices such as traps, bait stations, and the like. Such bait compositions may be in the form of granules comprising (a) an active ingredient, i.e. a biologically effective amount of a compound of formula 1 , an N -oxide or a salt thereof; (b) one or more food materials; optionally (c) an attractant, and optionally (d) one or more wetting agents. Of note are granules or bait compositions comprising between about 0.001%-5% active ingredient, between about 40%-99% food material and/or attractant; and optionally between about 0.05% and 10% of wetting agents which are effective in controlling soil invertebrate pests at very low application rates, especially at doses of active ingredient which are lethal by ingestion rather than by direct contact . Some food materials can be used both as a food source and as an attractant. Food materials include carbohydrates, proteins and lipids. Examples of food materials are vegetable powders, sugars, starches, animal fats, vegetable oils, yeast extracts and milk solids. Examples of attractants are flavor enhancers and flavoring agents, such as fruit or plant extracts, spices, or other animal or plant components, pheromones, or other agents known to attract target invertebrate pests. Examples of humectants (ie water retaining agents) are glycols and other polyols, glycerin and sorbitol. Of note are bait compositions (and methods of using such bait compositions) for controlling at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. A device for controlling invertebrate pests may comprise the bait composition of the present invention and a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to allow passage of the invertebrate pest An opening that enables the invertebrate pest to access the bait composition from a location external to the enclosure, and wherein the enclosure is further adapted to be placed in or near a likely or known locus of the invertebrate pest.
可在沒有其他輔助劑的情況下施加本揭露之化合物，但是最常見的施加係施加製劑，該製劑包含一種或多種活性成分與合適的載體、稀釋劑和表面活性劑，並且根據所設想的最終用途有可能與食物組合。一種施加方法關於將本揭露之化合物的水分散體或精煉油溶液噴霧。與噴霧油、噴霧油濃縮液、黏展劑、輔助劑、其他溶劑和胡椒基丁醚的組合通常增強化合物功效。對於非農學用途，此類噴霧可從噴霧容器諸如罐、瓶或其他容器中借助於泵進行施加，或藉由將噴霧從加壓容器例如加壓氣溶膠噴霧罐中釋放出來進行施加。此類噴霧組成物可採取多種形式，例如噴霧、薄霧、泡沫、煙霧或塵霧。因此，根據具體情況，此類噴霧組成物可進一步包含推進劑、發泡劑等。值得注意的是包含生物學有效量的本揭露之化合物或組成物以及載體的噴霧組成物。此種噴霧組成物的一個實施方式包含生物學有效量的本揭露之化合物或組成物以及推進劑。代表性推進劑包括但不限於甲烷、乙烷、丙烷、丁烷、異丁烷、丁烯、戊烷、異戊烷、新戊烷、戊烯、氫氟烴、氯氟烴、二甲醚和前述的混合物。值得注意的是用於防治至少一種選自以下群組的無脊椎害蟲的噴霧組成物（和使用由噴霧容器分配的此種噴霧組成物之方法），該群組由以下各項組成：蚊子、蚋、廄螯蠅、鹿虻、馬蠅、胡蜂、小黃蜂、大黃蜂、蜱蟲、蜘蛛、螞蟻、蠓等，包括單獨地或組合地。The compounds of the present disclosure can be applied without other auxiliaries, but the most common application is to apply a formulation comprising one or more active ingredients together with suitable carriers, diluents and surfactants, and according to the envisaged final Use is possible in combination with food. One method of application involves spraying an aqueous dispersion or refined oil solution of a compound of the present disclosure. Combinations with spray oils, spray oil concentrates, viscospreaders, adjuvants, other solvents and piperonyl butoxide generally enhance compound efficacy. For non-agricultural uses, such sprays may be applied from a spray container such as a can, bottle or other container with the aid of a pump, or by releasing the spray from a pressurized container, such as a pressurized aerosol spray can. Such spray compositions may take various forms, for example spray, mist, foam, mist or dust. Therefore, such a spray composition may further include a propellant, a foaming agent, etc. according to specific circumstances. Of note are spray compositions comprising a biologically effective amount of a compound or composition of the present disclosure and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or composition of the present disclosure 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 the aforementioned mixture. Of note are spray compositions (and methods of using such spray compositions dispensed from spray containers) for controlling at least one invertebrate pest selected from the group consisting of mosquitoes, Gnats, gnat flies, stag flies, horseflies, wasps, wasps, hornets, ticks, spiders, ants, midges, etc., singly or in combination.
本揭露之一個實施方式關於一種用於防治無脊椎害蟲之方法，該方法包括用水稀釋本揭露之殺害蟲組成物（與表面活性劑、固體稀釋劑和液體稀釋劑一起配製的式 1的化合物，或式 1的化合物和至少一種其他殺害蟲劑的配製的混合物），以及視需要添加輔助劑以形成稀釋的組成物，以及使無脊椎害蟲或其環境與有效量的所述稀釋的組成物接觸。 One embodiment of the present disclosure relates to a method for controlling invertebrate pests, the method comprising diluting the pesticidal composition of the present disclosure (the compound of formula 1 formulated together with a surfactant, a solid diluent and a liquid diluent, or a compound of formula 1 and at least one other insecticide), and if necessary, adding adjuvants to form a diluted composition, and contacting the invertebrate pest or its environment with an effective amount of the diluted composition .
儘管藉由用水稀釋足夠濃度的本發明之殺害蟲組成物形成的噴霧組成物可提供充分的防治無脊椎害蟲的功效，但單獨配製的輔助劑產品也可被添加到噴霧槽混合物中。該等附加的輔助劑通常被稱為「噴霧輔助劑」或「槽-混合輔助劑」，並且包含在噴霧槽中混合以改善殺害蟲劑的性能或改變噴霧混合物的物理特性的任何物質。輔助劑可以是表面活性劑、乳化劑、石油基作物油、作物衍生的種子油、酸化劑、緩衝液、增稠劑或消泡劑。輔助劑被用於增強功效（例如，生體可用率、黏附性、滲透性、覆蓋均勻度和保護耐久性），或最小化或消除與不相容性、發泡、飄移、蒸發、揮發和降解相關聯的噴霧施加問題。為了獲得最佳性能，關於活性成分的特性、製劑和目標（例如，作物、昆蟲害蟲）來選擇輔助劑。Although spray compositions formed by diluting sufficient concentrations of the pesticidal compositions of this invention with water provide adequate control of invertebrate pests, separately formulated adjuvant products may also be added to the spray tank mixture. Such additional adjuvants are commonly referred to as "spray adjuvants" or "tank-mix adjuvants" and include any substance that is mixed in a spray tank to improve the performance of the insecticide or to alter the physical characteristics of the spray mixture. Adjuvants may be surfactants, emulsifiers, petroleum-based crop oils, crop-derived seed oils, acidulants, buffers, thickeners or antifoams. Adjuvants are used to enhance efficacy (e.g., bioavailability, adhesion, penetration, uniformity of coverage, and durability of protection), or to minimize or eliminate problems related to incompatibility, foaming, drift, evaporation, volatilization, and Degradation associated with spray application problems. Adjuvants are chosen with regard to the identity, formulation and target (eg crop, insect pest) of the active ingredient for optimum performance.
在噴霧輔助劑之中，最通常使用油（包括作物油、作物油濃縮物、植物油濃縮物和甲基化種子油濃縮物）來改善殺害蟲劑的功效，這可能是藉由促進更均勻且一致的噴霧沈積來實現的。在其中可能由油或其他與水不混溶的液體引起的植物毒性係重要的情況下，由本揭露之組成物製備的噴霧組成物通常將不含油基噴霧輔助劑。然而，在其中由油基噴霧輔助劑造成的植物毒性在商業上不重要的情況下，由本發明組成物的組成物製備的噴霧組成物也可含有油基噴霧輔助劑，這可潛在地進一步增加對無脊椎害蟲的防治以及耐雨性。Among spray adjuvants, oils (including crop oils, crop oil concentrates, vegetable oil concentrates, and methylated seed oil concentrates) are most commonly used to improve the efficacy of insecticides, possibly by promoting more uniform and Consistent spray deposition is achieved. In cases where phytotoxicity, which may be caused by oils or other water-immiscible liquids, is important, spray compositions prepared from compositions of the present disclosure will generally be free of oil-based spray adjuvants. However, in cases where the phytotoxicity caused by the oil-based spray adjuvant is not commercially important, the spray composition prepared from the composition of the composition of the present invention may also contain the oil-based spray adjuvant, which may potentially further increase the Invertebrate pest control and rain tolerance.
確定為「作物油」的產品典型地含有95%至98%的石蠟或石腦油基石油和1%至2%的一種或多種用作乳化劑的表面活性劑。確定為「作物油濃縮物」的產品典型地由80%至85%的可乳化石油基油和15%至20%的非離子表面活性劑組成。正確地確定為「植物油濃縮物」的產品典型地由80%至85%的植物油（即種子油或果實油，最通常來自棉、亞麻籽、大豆或向日葵）和15%至20%的非離子表面活性劑組成。可藉由用典型地衍生自植物油的脂肪酸的甲酯替代植物油來改善輔助劑性能。甲基化種子油濃縮物的實例包括MSO ®濃縮物（UAP-洛弗蘭德產品公司（UAP-Loveland Products, Inc.））和Premium MSO甲基化噴霧油（海倫娜化學公司（Helena Chemical Company））。 Products identified as "crop oils" typically contain 95% to 98% paraffinic or naphtha based petroleum and 1% to 2% of one or more surfactants used as emulsifiers. Products identified as "crop oil concentrates" typically consist of 80% to 85% emulsifiable petroleum base oil and 15% to 20% nonionic surfactant. Products properly identified as "vegetable oil concentrates" typically consist of 80% to 85% vegetable oil (i.e. seed or fruit oil, most often from cotton, linseed, soybean or sunflower) and 15% to 20% nonionic Surfactant composition. Adjuvant properties can be improved by replacing vegetable oils with methyl esters of fatty acids typically derived from vegetable oils. Examples of methylated seed oil concentrates include MSO® Concentrate (UAP-Loveland Products, Inc.) and Premium MSO Methylated Spray Oil (Helena Chemical Company )).
添加到噴霧混合物中的輔助劑的量通常不超過按體積計約2.5%，並且更典型地該量為按體積計從約0.1%至約1%。添加到噴霧混合物中的輔助劑的施加量典型地在每公頃約1 L至5 L之間。噴霧輔助劑的代表性實例包括：Adigor ®（先正達公司（Syngenta））液烴中的47%甲基化菜籽油、Silwet ®（海倫娜化學公司）聚伸烷基氧化物修飾的七甲基三矽氧烷以及Assist ®（巴斯夫公司（BASF））83%石蠟基礦物油中的17%表面活性劑共混物。 The amount of adjuvant added to the spray mixture will generally not exceed about 2.5% by volume, and more typically the amount will be from about 0.1% to about 1% by volume. Adjuvants are typically added to the spray mixture at application rates of between about 1 L and 5 L per hectare. Representative examples of spray adjuvants include: Adigor ® (Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Silwet ® (Helena Chemicals) polyalkylene oxide modified hepta Methyltrisiloxane and Assist ® (BASF) 17% surfactant blend in 83% paraffinic mineral oil.
非農學應用包括藉由向待保護動物（特別是脊椎動物，更特別地恒溫脊椎動物（例如，哺乳動物或鳥類）並且最特別地哺乳動物）施用殺寄生蟲有效（即生物學有效）量的本揭露化合物（典型地呈被配製用於獸醫用途的組成物的形式）來保護動物免受無脊椎寄生性害蟲的侵害。因此，值得注意的是用於保護動物之方法，該方法包括向動物施用殺寄生蟲有效量的本揭露之化合物。如在本揭露和請求項中所提及，術語「殺寄生蟲的」和「殺寄生蟲地」係指對無脊椎寄生性害蟲的可觀察影響，以保護動物免受害蟲的侵害。殺寄生蟲效果典型地與減少目標無脊椎寄生性害蟲的出現或活動有關。此類對害蟲的影響包括壞死、死亡、生長遲緩、移動性降低或留在宿主動物身上或體內的能力降低、取食減少和生殖抑制。該等對無脊椎寄生性害蟲的影響防治（包括預防、減少或消除）動物的寄生蟲侵害或感染。藉由向待保護動物施用殺寄生蟲有效量的本揭露之化合物來防治的無脊椎寄生性害蟲的實例包括體表寄生蟲（節肢動物、蟎類（acarines）等）和體內寄生蟲（蠕蟲，例如線蟲、吸蟲、絛蟲、棘頭動物等）。特別地，本揭露之化合物對包括以下的體表寄生蟲有效：蠅，諸如角蠅（ Haematobia (Lyperosia) irritans）、廄螯蠅（ Stomoxys calcitrans）、蚋（蚋屬（ Simulium）物種）、采采蠅（舌蠅屬（ Glossina）物種）、頭蠅（ Hydrotaea irritans）、秋家蠅（ Musca autumnalis））、家蠅（ Musca domestica）、簡莫蠅（ Morellia simplex）、馬蠅（虻屬物種）、牛皮蠅（ Hypoderma bovis）、紋皮蠅（ Hypoderma lineatum）、絲光綠蠅（ Lucilia sericata）、綠頭蒼蠅（ Lucilia cuprina）、麗蠅（麗蠅屬（ Calliphora）物種）、原伏蠅屬（ Protophormia）物種、羊狂蠅（ Oestrus ovis）、蠓（庫蠓屬（ Culicoides）物種）、馬虱蠅（ Hippobosca equine）、腸胃蠅（ Gastrophilus instestinalis）、赤馬胃蠅（ Gastrophilus haemorrhoidalis）和鼻胃蠅（ Gastrophilus naslis）；虱，諸如牛毛虱（ Bovicola (Damalinia) bovis）、馬毛虱（ Bovicola equi）、驢血虱（ Haematopinus asini）、貓毛虱（ Felicola subrostratus）、袋鼠虱（ Heterodoxus spiniger）、棘顎虱（ Lignonathus setosus）和犬毛虱（ Trichodectes canis）；羊蜱蠅，諸如綿羊虱蠅；蟎，諸如癢蟎屬（ Psoroptes）物種、人疥蟎（ Sarcoptes scabei）、牛皮癢蟎（ Chorioptes bovis）、馬蠕形蟎（ Demodex equi）、姬螯蟎屬（ Cheyletiella）物種、背肛蟎（ Notoedres cati）、恙蟎屬（ Trombicula）物種和耳蟎（ Otodectes cyanotis）；蜱，諸如硬蜱屬（ Ixodes）物種、牛蜱屬（ Boophilus）物種、扇頭蜱屬（ Rhipicephalus）物種、花蜱屬（ Amblyomma）物種、革蜱屬（ Dermacentor）物種、璃眼蜱屬（ Hyalomma）物種和血蜱屬（ Haemaphysalis）物種；和跳蚤，諸如貓蚤（ Ctenocephalides felis）和犬蚤（ Ctenocephalides canis）。 Non-agronomic applications include administering a parasiticidally effective (i.e. biologically effective) amount of Compounds of the present disclosure, typically in the form of compositions formulated for veterinary use, protect animals from invertebrate parasitic pests. Of note, therefore, are methods for the protection of animals comprising administering to the animal a parasiticidally effective amount of a compound of the present disclosure. As referred to in the present disclosure and claims, the terms "parasiticidal" and "parasiticidal" refer to an observable effect on an invertebrate parasitic pest to protect animals from the pest. Parasiticidal effects are typically associated with reducing the presence or activity of target invertebrate parasitic pests. Such effects on the pest include necrosis, death, growth retardation, reduced mobility or ability to remain on or in the host animal, reduced feeding and reproductive inhibition. Such Effects on Invertebrate Parasitic Pests Control (including prevention, reduction or elimination) of parasitic infestation or infection in animals. Examples of invertebrate parasitic pests that can be controlled by administering a parasiticidally effective amount of a compound of the present disclosure to an animal to be protected include ectoparasites (arthropods, acarines, etc.) and endoparasites (helminths , such as nematodes, trematodes, tapeworms, acanthocephalans, etc.). In particular, the compounds of the present disclosure are effective against ectoparasites including flies such as Haematobia (Lyperosia) irritans , Stomoxys calcitrans , gnats ( Simulium species), flies ( Glossina species), head flies ( Hydrotaea irritans ), autumn houseflies ( Musca autumnalis )), house flies ( Musca domestica ), morellia simplex , horseflies (Afly species), Hypoderma bovis , Hypoderma lineatum , Lucilia sericata , Lucilia cuprina , Blowflies ( Calliphora species), Protophormia species, Oestrus ovis , midges ( Culicoides species), horse lice ( Hippobosca equine ), gastrophilus insectinalis , gastrophilus haemorrhoidalis and gastrophilus naslis ); lice, such as the cow lice ( Bovicola (Damalinia) bovis ), the horse lice ( Bovicola equi ), the donkey blood lice ( Haematopinus asini ), the cat lice ( Felicola subrostratus ), the kangaroo lice ( Heterodoxus spiniger ), the spine lice ( Lignothus setosus ) and dog hair lice ( Trichodectes canis ); sheep ticks, such as sheep lice; mites, such as species of Psoroptes , Sarcoptes scabei , Chorioptes bovis , Demodex equine ( Demodex equi ), Cheyletiella species, Notoedres cati , Trombicula species, and Otodectes cyanotis ; ticks such as Ixodes species, cattle ticks Genus ( Boophilus ) species, Rhipicephalus ( Rhipicephalus ) species, Amblyomma species, Dermacentor species, Hyalomma species, and Haemaphysalis species; and fleas, such as cat fleas ( Ctenocephalides felis ) and dog fleas ( Ctenocephalides canis ).
獸醫部門中的非農學應用係藉由常規手段，諸如以例如片劑、膠囊、飲料、浸液製品、顆粒劑、糊劑、大丸藥、喂入程序或栓劑的形式腸道內施用；或諸如藉由注射（包括肌內注射、皮下注射、靜脈內注射、腹膜內注射）或植入物的腸胃外施用；鼻腔施用；例如以浸泡或浸漬、噴霧、洗滌、粉末塗層、或施加於動物的一小塊區域和藉由包含本揭露之化合物或組成物的物品（諸如頸圈、耳標、尾帶、肢帶或韁繩）的形式局部施用。Non-agronomic applications in the veterinary sector are by conventional means, such as enteral administration in the form of e.g. tablets, capsules, drinks, infusions, granules, pastes, boluses, feeding procedures or suppositories; or such as Parenteral administration by injection (including intramuscular injection, subcutaneous injection, intravenous injection, intraperitoneal injection) or implant; nasal administration; for example, by soaking or dipping, spraying, washing, powder coating, or applying to animals and topical application in the form of articles, such as collars, ear tags, tailbands, limb bands or bridles, comprising a compound or composition of the present disclosure.
典型地，根據本揭露之殺寄生蟲組成物包含式 1的化合物、其 N-氧化物或鹽與一種或多種藥學上或獸醫學上可接受的載體的混合物，該一種或多種藥學上或獸醫學上可接受的載體包含關於預期施用途徑（例如，口服、局部或腸胃外施用，諸如注射）並且根據標準操作選擇的賦形劑和助劑。另外，基於與組成物中的一種或多種活性成分的相容性選擇合適的載體，包括諸如相對於pH和水分含量的穩定性的考慮。因此，值得注意的是用於保護動物免受無脊椎寄生性害蟲侵害的組成物，該組成物包含殺寄生蟲有效量的本揭露之化合物和至少一種載體。 Typically, the parasiticidal composition according to the present disclosure comprises a compound of Formula 1 , its N -oxide or salt in admixture with one or more pharmaceutically or veterinarily acceptable carriers, the one or more pharmaceutically or veterinarily A medically acceptable carrier comprises excipients and auxiliaries selected for the intended route of administration (eg, oral, topical or parenteral administration, such as injection) and according to standard practice. Additionally, selection of an appropriate carrier is based on compatibility with one or more active ingredients in the composition, including considerations such as stability with respect to pH and moisture content. Of note, therefore, are compositions for protecting animals from invertebrate parasitic pests comprising a parasiticidally effective amount of a compound of the present disclosure and at least one carrier.
對於包括靜脈內注射、肌內注射和皮下注射的腸胃外施用，本揭露之化合物可在油性或水性媒介物中以懸浮液、溶液或乳液的形式配製，並且可含有諸如懸浮劑、穩定劑和/或分散劑的輔助劑。用於注射的藥物組成物包括水溶性形式的活性成分（例如，活性化合物的鹽）的水性溶液，較佳的是在含有其他賦形劑或助劑的生理相容性緩衝液中，如藥物製劑領域中已知的。For parenteral administration, including intravenous, intramuscular, and subcutaneous injections, the compounds of the present disclosure may be formulated as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain, for example, suspending agents, stabilizing agents, and / or auxiliaries for dispersants. Pharmaceutical compositions for injection comprise aqueous solutions of the active ingredient (e.g., a salt of the active compound) in water-soluble form, preferably in a physiologically compatible buffer with other excipients or auxiliaries, such as drug known in the art of formulation.
對於以溶液（最容易獲得的吸收形式）、乳液、懸浮液、糊劑、凝膠、膠囊、片劑、大丸藥、粉末、顆粒劑、瘤胃滯留和飼料/水/舔塊的形式口服施用，本揭露之化合物可以與本領域已知的適用於口服施用組成物的黏合劑/填料一起配製，諸如糖（例如，乳糖、蔗糖、甘露醇、山梨糖醇）、澱粉（例如，玉蜀黍澱粉、小麥澱粉、稻米澱粉、馬鈴薯澱粉）、纖維素和衍生物（例如，甲基纖維素、羧甲基纖維素、乙基羥基纖維素）、蛋白質衍生物（例如，玉米醇溶蛋白（zein）、明膠）和合成聚合物（例如，聚乙烯醇、聚乙烯吡咯啶酮）。如果需要，可以添加潤滑劑（例如硬脂酸鎂）、崩散劑（例如，交聯聚乙烯吡咯啶酮、瓊脂、褐藻酸）和染料或顏料。糊劑和凝膠通常還含有黏合劑（例如，阿拉伯膠、褐藻酸、膨潤土、纖維素、黃原膠、膠體矽酸鎂鋁），以説明保持組成物與口腔接觸而不易被排出。For oral administration in the form of solutions (the most readily available form for absorption), emulsions, suspensions, pastes, gels, capsules, tablets, boluses, powders, granules, ruminal retention and feed/water/lick blocks, The compounds of the present disclosure can be formulated with binders/fillers known in the art to be suitable for oral administration compositions, such as sugars (e.g., lactose, sucrose, mannitol, sorbitol), starches (e.g., maize starch, wheat starch, starch, rice starch, potato starch), cellulose and derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), protein derivatives (e.g., zein, gelatin ) and synthetic polymers (eg, polyvinyl alcohol, polyvinylpyrrolidone). Lubricants (eg, magnesium stearate), disintegrating agents (eg, crospovidone, agar, alginic acid) and dyes or pigments may be added, if desired. Pastes and gels often also contain binders (eg, acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesium aluminum silicate) to help keep the composition in contact with the oral cavity and not easily excreted.
如果殺寄生蟲組成物呈飼料濃縮物的形式，則載體典型地選自高性能飼料、飼料穀物或蛋白質濃縮物。除了殺寄生蟲活性成分之外，此類含有飼料濃縮物的組成物還可以包含促進動物健康或生長、改善屠宰用動物肉品質或以其他方式對動物飼養有用的添加劑。該等添加劑可包括例如維生素、抗生素、化學療法、抑菌劑、抑真菌劑、抗球蟲劑和激素。If the parasiticidal composition is in the form of a feed concentrate, the carrier is typically selected from high performance feed, feed grains or protein concentrates. Such feed concentrate-containing compositions may contain, in addition to parasiticidal active ingredients, additives that promote animal health or growth, improve meat quality of animals for slaughter, or are otherwise useful for animal husbandry. Such additives may include, for example, vitamins, antibiotics, chemotherapy, bacteriostats, fungicides, coccidiostats and hormones.
已發現本揭露化合物具有良好的藥物動力學和藥效學特性，從而藉由口服施用和攝取提供全身可用性。因此，在待保護的動物攝取後，血流中殺寄生蟲有效濃度的本揭露化合物保護經處理的動物免受吸血害蟲（諸如跳蚤、蜱蟲和虱）的侵害。因此，值得注意的是用於保護動物免受無脊椎寄生性害蟲侵害的呈用於口服施用的形式的組成物（即，除了殺寄生蟲有效量的本揭露之化合物外，還包含一種或多種選自適用於口服施用的黏合劑和填料的載體以及飼料濃縮物載體）。The compounds of the present disclosure have been found to have favorable pharmacokinetic and pharmacodynamic properties, thereby providing systemic availability by oral administration and ingestion. Thus, after ingestion by the animal to be protected, a parasiticidally effective concentration of the compounds of the disclosure in the bloodstream protects the treated animal from blood-sucking pests such as fleas, ticks and lice. Therefore, it is worth noting that compositions for the protection of animals from invertebrate parasitic pests are in a form intended for oral administration (i.e., comprising, in addition to a parasiticidally effective amount of a compound of the present disclosure, one or more Carriers selected from binders and fillers suitable for oral administration and feed concentrate carriers).
用於局部施用的製劑典型地呈粉末、乳膏、懸浮液、噴霧、乳液、泡沫、糊劑、氣溶膠、軟膏、藥膏或凝膠的形式。更典型地，局部製劑係水溶性溶液，其可以呈濃縮物的形式，在使用前稀釋。適用於局部施用的殺寄生蟲組成物典型地包含本揭露之化合物和一種或多種局部合適的載體。在將殺寄生蟲組成物作為線或點（即「點樣」處理）局部施加至動物的外部時，活性成分遷移到動物的表面以覆蓋其大部分或全部外表面區域。因此，經處理的動物特別地被保護免受以動物表皮為食的無脊椎害蟲（諸如蜱蟲、跳蚤和虱）的侵害。因此，用於局部施用的製劑通常包含至少一種有機溶劑，以促進活性成分在動物皮膚上的運輸和/或滲透到動物表皮內。在此類製劑中通常用作載體的溶劑包括丙二醇、石蠟、芳族化合物、酯（諸如肉豆蔻酸異丙酯）、乙二醇醚和醇（諸如乙醇和正丙醇）。Formulations for topical administration are typically in the form of powders, creams, suspensions, sprays, emulsions, foams, pastes, aerosols, ointments, salves or gels. More typically, topical formulations are water-soluble solutions, which may be in the form of concentrates, to be diluted prior to use. Parasiticidal compositions suitable for topical application typically comprise a compound of the present disclosure and one or more topically suitable carriers. When a parasiticidal composition is topically applied to the exterior of an animal as a line or spot (ie, a "spot" treatment), the active ingredient migrates to the surface of the animal to cover most or all of its exterior surface area. Thus, the treated animals are especially protected from invertebrate pests such as ticks, fleas and lice that feed on the animal's cuticle. Accordingly, formulations for topical application generally contain at least one organic solvent to facilitate transport of the active ingredient on the skin of the animal and/or penetration into the epidermis of the animal. Solvents commonly used as carriers in such formulations include propylene glycol, paraffins, aromatics, esters such as isopropyl myristate, glycol ethers and alcohols such as ethanol and n-propanol.
有效防治所需的施加量（即「生物學有效量」）將取決於諸如以下的因素：待防治的無脊椎動物種類、害蟲的生命週期、生命階段、其大小、位置、一年中的時間、宿主作物或動物、取食行為、交配行為、環境濕度、溫度。在正常情況下，每公頃約0.01 kg至2 kg活性成分的施加量足以在農業生態系統中防治害蟲，但是低至0.0001 kg/公頃可能就足夠，或可能需要高達8 kg/公頃。對於非農學應用，有效的使用量將在約1.0 mg/平方米至50 mg/平方米之間，但是低至0.1 mg/平方米可能就足夠，或可能需要高達150 mg/平方米。熟悉該項技術者可以容易地確定期望的無脊椎害蟲防治水平所必需的生物學有效量。The amount of application required for effective control (i.e. the "biologically effective amount") will depend on factors such as: the species of invertebrate to be controlled, the life cycle of the pest, its life stage, its size, location, time of year , host crop or animal, feeding behavior, mating behavior, ambient humidity, temperature. Application rates of approximately 0.01 kg to 2 kg of active ingredient per hectare are normally adequate for pest control in agroecosystems, but as little as 0.0001 kg/ha may be sufficient, or as high as 8 kg/ha may be required. For non-agronomic applications, effective use levels will be between about 1.0 mg/m2 and 50 mg/m2, but as low as 0.1 mg/m2 may be sufficient, or as high as 150 mg/m2 may be required. Those skilled in the art can readily determine the biologically effective amount necessary for the desired level of invertebrate pest control.
通常對於獸醫用途，將式 1的化合物、其 N-氧化物或鹽以殺寄生蟲有效量施用到待保護以免受無脊椎寄生性害蟲侵害的動物。殺寄生蟲有效量係達到可觀察效果（減少目標無脊椎寄生性害蟲的出現或活動）所需的活性成分的量。熟悉該項技術者將理解，殺寄生蟲有效劑量可因本揭露之各種化合物和組成物、期望的殺寄生蟲效果和持續時間、目標無脊椎害蟲種類、待保護的動物、施加模式等而變化，並且實現特定結果所需的量可以藉由簡單的實驗來確定。 Typically for veterinary use, a compound of formula 1 , its N -oxide or salt is administered in a parasiticidally effective amount to an animal to be protected from invertebrate parasitic pests. A parasiticidally effective amount is the amount of active ingredient required to achieve an observable effect (reduction of the presence or activity of the target invertebrate parasitic pest). Those skilled in the art will understand that parasiticidally effective amounts may vary with the various compounds and compositions of the present disclosure, the desired parasiticidal effect and duration, the target invertebrate pest species, the animal to be protected, the mode of application, etc. , and the amount required to achieve a particular result can be determined by simple experimentation.
對於恒溫動物的口服施用，本揭露之化合物的日劑量典型地為動物體重的從約0.01 mg/kg至約100 mg/kg，更典型地從約0.5 mg/kg至約100 mg/kg。對於局部（例如，表皮）施用，浸漬液和噴霧典型地含有從約0.5 ppm至約5000 ppm，更典型地從約1 ppm至約3000 ppm的本揭露化合物。For oral administration to homeothermic animals, the daily dosage of the disclosed compounds is typically from about 0.01 mg/kg to about 100 mg/kg, more typically from about 0.5 mg/kg to about 100 mg/kg, of the animal's body weight. For topical (eg, epidermal) application, dips and sprays typically contain from about 0.5 ppm to about 5000 ppm, more typically from about 1 ppm to about 3000 ppm, of the disclosed compounds.
藉由本文所述之方法製備的本揭露之化合物示於索引表A-F中。Me意指甲基，OMe意指甲氧基，Et意指乙基， i-Pr意指異丙基， i-OPr意指異丙氧基（即-OCH(CH 3) 2）， c-Pr意指環丙基， t-Bu意指三級丁基，並且Ph意指苯基。縮寫「Cmpd. No.」代表「化合物編號」，而縮寫「Ex.」代表「實例」並且後面係數字，該數字表示化合物在哪個實例中製備。縮寫「m.p.」代表熔點。結構片段中的波浪線或「-」表示片段與分子其餘部分的附接點。在「MS」欄中報導的數值係藉由向具有最高同位素豐度的分子添加H +（分子量為1）形成的最高同位素豐度帶正電荷的母離子（M+1）的分子量，或藉由損失H +（分子量為1）形成的最高同位素豐度帶負電荷的離子（M-1）的分子量。未報導含有一種或多種較低豐度的較高原子量同位素（例如 37Cl、 81Br）的分子離子的存在。使用電灑電離（ESI）或大氣壓化學電離（APCI）藉由質譜法觀察所報告的MS峰。 Compounds of the disclosure prepared by the methods described herein are shown in Index Tables AF. Me means methyl, OMe means methoxy, Et means ethyl, i -Pr means isopropyl, i -OPr means isopropoxy (i.e. -OCH(CH 3 ) 2 ), c -Pr means cyclopropyl, t -Bu means tertiary butyl, and Ph means phenyl. The abbreviation "Cmpd. No." stands for "Compound Number" and the abbreviation "Ex." stands for "Example" and is followed by a number indicating in which Example the compound was prepared. The abbreviation "mp" stands for melting point. A tilde or "-" in a structural fragment indicates the point of attachment of the fragment to the rest of the molecule. The value reported in the "MS" column is the molecular weight of the most isotopically abundant positively charged precursor ion (M+1) formed by adding H + (molecular weight 1) to the most isotopically abundant molecule, or by The molecular weight of the most isotopically abundant negatively charged ion (M-1) formed by the loss of H + (molecular weight 1). The presence of molecular ions containing one or more of the lower abundance isotopes of higher atomic weight (eg 37 Cl, 81 Br) has not been reported. The reported MS peaks were observed by mass spectrometry using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI).
除非另外指明，否則索引表A-F和X1-X2中的化合物係式 1 i 和 1 ii 的化合物的混合物。 Unless otherwise indicated, the compounds in Index Tables AF and X1-X2 are mixtures of compounds of formulas 1 i and 1 ii .
索引表A
(R
JC)
r欄中的連接號「-」意指不存在R
JC取代基並且剩餘的碳化合價被氫原子佔據。
注釋A1：鏡像異構物[α] D 20-62.8°（濃度= 0.50，在甲醇中）。 Note A1: Enantiomer [α] D 20 -62.8° (concentration = 0.50 in methanol).
注釋A2：鏡像異構物[α] D 20+66.8°（濃度= 0.50，在甲醇中）。 Note A2: Enantiomer [α] D 20 +66.8° (concentration = 0.50 in methanol).
注釋A3：鏡像異構物[α] D 25+47.98°（濃度= 0.20，在甲醇中）。 Note A3: Enantiomer [α] D 25 +47.98° (concentration = 0.20 in methanol).
注釋A4：鏡像異構物[α] D 25-77.78°（濃度= 0.20，在甲醇中）。 Note A4: Enantiomer [α] D 25 -77.78° (concentration = 0.20 in methanol).
注釋A5：鏡像異構物[α] D 25-66.44°（濃度= 0.20，在甲醇中）。 Note A5: Enantiomer [α] D 25 -66.44° (concentration = 0.20 in methanol).
注釋A6：鏡像異構物[α] D 25+64.46°（濃度= 0.20，在甲醇中）。 Note A6: Enantiomer [α] D 25 +64.46° (concentration = 0.20 in methanol).
注釋A7：鏡像異構物[α] D 25+59.45°（濃度= 0.20，在甲醇中）。 Note A7: Enantiomer [α] D 25 +59.45° (concentration = 0.20 in methanol).
注釋A8：鏡像異構物[α] D 25-55.60°（濃度= 0.20，在甲醇中）。 Note A8: Enantiomer [α] D 25 -55.60° (concentration = 0.20 in methanol).
索引表B
(R
JC)
r欄中的連接號「-」意指不存在R
JC取代基並且剩餘的碳化合價被氫原子佔據。
注釋B1：鏡像異構物[α] D 20+74°（濃度= 0.50，在甲醇中）。 Note B1: Enantiomer [α] D 20 +74° (concentration = 0.50 in methanol).
注釋B2：鏡像異構物[α] D 20-76°（濃度= 0.50，在甲醇中）。 Note B2: Enantiomer [α] D 20 -76° (concentration = 0.50 in methanol).
索引表C
(R
JC)
r欄中的連接號「-」意指不存在R
JC取代基並且剩餘的碳化合價被氫原子佔據。
注釋C1：鏡像異構物[α] D 20+64°（濃度= 0.50，在甲醇中）。 Note C1: Enantiomer [α] D 20 +64° (concentration = 0.50 in methanol).
注釋C2：鏡像異構物[α] D 20-63°（濃度= 0.50，在甲醇中）。 Note C2: Enantiomer [α] D 20 -63° (concentration = 0.50 in methanol).
注釋C3：鏡像異構物[α] D 25-45.58°（濃度= 0.20，在甲醇中）。 Note C3: Enantiomer [α] D 25 -45.58° (concentration = 0.20 in methanol).
注釋C4：鏡像異構物[α] D 25-45.10°（濃度= 0.20，在甲醇中）。 Note C4: Enantiomer [α] D 25 -45.10° (concentration = 0.20 in methanol).
索引表D
(R
JC)
r欄中的連接號「-」意指不存在R
JC取代基並且剩餘的碳化合價被氫原子佔據。
索引表E
索引表F
(R
JC)
r欄中的連接號「-」意指不存在R
JC取代基並且剩餘的碳化合價被氫原子佔據。
以下測試證明了本揭露之化合物對特定害蟲的防治功效。「防治功效」表示導致取食顯著降低的對無脊椎害蟲的發育的抑制（包括死亡率）。然而，由化合物提供的害蟲防治保護不限於該等種類。化合物描述參見索引表A-F。The following tests demonstrate the control efficacy of the disclosed compounds against specific pests. "Control efficacy" means inhibition of development (including mortality) of an invertebrate pest resulting in a significant reduction in feeding. However, the pest control protection afforded by the compounds is not limited to these species. See Index Tables A-F for compound descriptions.
生物學實例biological example
用於測試A-G的配製和噴霧方法學Formulation and spray methodology used for testing A-G
使用含有10%丙酮、90%水和300 ppm Activator 90®非離子表面活性劑（美國科羅拉多州洛弗蘭德的洛弗蘭德產品公司（Loveland Products, Loveland, Colorado, USA））的溶液來配製測試化合物。配製的化合物藉由定位在每個測試單元的頂部上方1.27 cm（0.5英吋）的霧化噴嘴以1 mL的液體施加。測試化合物以指定的速率進行噴霧，並且每次測試重複三次。Prepared using a solution containing 10% acetone, 90% water, and 300 ppm Activator 90® nonionic surfactant (Loveland Products, Loveland, Colorado, USA) Test compound. The formulated compounds were applied as 1 mL of liquid through an atomizing nozzle positioned 1.27 cm (0.5 inches) above the top of each test unit. Test compounds were sprayed at the indicated rates and each test was repeated in triplicate.
測試ATest A
為了藉由接觸和/或內吸手段評估對小菜蛾的防治，每個測試單元由內部具有10至12天齡芥子植株的小開口容器組成。To assess control of diamondback moth by contact and/or systemic means, each test unit consisted of a small open container with 10 to 12 day old mustard plants inside.
如上所述配製測試化合物並以250、50和2 ppm噴霧，重複三次。 噴霧後，使測試單元乾燥1小時，之後用30-50隻初孵幼蟲對它們進行侵害。將黑色遮蔽蓋放置在每個容器的頂部上。將測試單元在24°C-25°C和70%相對濕度的生長室中保持六天。然後基於所消耗的葉子視覺評估植株取食損害，並評估幼蟲的死亡率。Test compounds were formulated as above and sprayed at 250, 50 and 2 ppm in triplicate. After spraying, the test units were allowed to dry for 1 hour before they were infested with 30-50 naive larvae. A black masking cap was placed on top of each container. The test units were kept in a growth chamber at 24°C-25°C and 70% relative humidity for six days. Plant feeding damage was then assessed visually based on the leaves consumed, and larval mortality was assessed.
在250 ppm下所測試的式 1的化合物中，以下提供了非常好至優異的防治功效水平（20%或更小的取食損害）：1、3、16、23、27、43、81、84、136、137、128、139、167、176、178、197、206、221、228、231、233、235、240和252。 Of the compounds of Formula 1 tested at 250 ppm, the following provided very good to excellent levels of control efficacy (20% or less feeding damage): 1, 3, 16, 23, 27, 43, 81, 84, 136, 137, 128, 139, 167, 176, 178, 197, 206, 221, 228, 231, 233, 235, 240 and 252.
在50 ppm下所測試的式 1的化合物中，以下提供了非常好至優異的防治功效水平（20%或更小的取食損害）：27和221。 Of the compounds of Formula 1 tested at 50 ppm, the following provided very good to excellent levels of control efficacy (20% or less feeding damage): 27 and 221.
在2 ppm下所測試的式 1的化合物中，以下提供了非常好至優異的防治功效水平（20%或更小的取食損害）：27。 Of the compounds of Formula 1 tested at 2 ppm, the following provided very good to excellent levels of control efficacy (20% or less feeding damage): 27.
測試Btest B
為了評價對秋夜蛾（ Spodoptera frugiperda(J.E. Smith)）的防治，測試單元由內部具有4至5天齡玉米（玉蜀黍）植株的小開口容器組成。這在一塊昆蟲食物上用10至15隻一日齡幼蟲進行預侵害。 To evaluate control of fall armyworm ( Spodoptera frugiperda (JE Smith)), the test unit consisted of a small open container with a 4- to 5-day-old corn (maize) plant inside. This is pre-infested with 10 to 15 day-old larvae on a piece of insect food.
如上所述配製測試化合物並以50和2 ppm噴霧，重複三次。 在噴霧所配製的測試化合物後，將測試單元維持在25°C和70%相對濕度的生長室中6天。然後基於所消耗的葉子視覺評估植株取食損害，並評估幼蟲的死亡率。Test compounds were formulated as above and sprayed at 50 and 2 ppm in triplicate. After spraying the formulated test compounds, the test cells were maintained in a growth chamber at 25°C and 70% relative humidity for 6 days. Plant feeding damage was then assessed visually based on the leaves consumed, and larval mortality was assessed.
在50 ppm下所測試的式 1的化合物中，以下提供了非常好至優異的防治功效水平（20%或更小的取食損害）：27和221。 Of the compounds of Formula 1 tested at 50 ppm, the following provided very good to excellent levels of control efficacy (20% or less feeding damage): 27 and 221.
在2 ppm下所測試的式 1的化合物中，以下提供了非常好至優異的防治功效水平（20%或更小的取食損害）：27。 Of the compounds of Formula 1 tested at 2 ppm, the following provided very good to excellent levels of control efficacy (20% or less feeding damage): 27.
測試Ctest C
為了藉由接觸和/或內吸手段評估對玉米飛虱的防治，測試單元由內部具有3至4天齡玉米（玉蜀黍）植株的小開口容器組成。將白砂添加到土壤的頂部，之後施加測試化合物。To evaluate control of corn planthopper by contact and/or systemic means, the test unit consisted of a small open container with a 3 to 4 day old corn (maize) plant inside. White sand was added to the top of the soil, after which the test compound was applied.
如上所述配製測試化合物並以250和50 ppm噴霧，重複三次。將配製的測試化合物進行噴霧後，使測試單元乾燥1 h，之後用約15-20隻若蟲（18至21天齡）對它們進行後侵害。將黑色遮蔽蓋放置在每個測試單元的頂部上，並且將測試單元在22°C至24°C和50%-70%相對濕度的生長室中保持6天。然後在視覺上評估每個測試單元的昆蟲死亡率。Test compounds were formulated as above and sprayed at 250 and 50 ppm in triplicate. After spraying the formulated test compounds, the test units were allowed to dry for 1 h before they were post-infested with about 15-20 nymphs (18 to 21 days old). A black shadow cover was placed on top of each test unit and the test unit was maintained in a growth chamber at 22°C to 24°C and 50%-70% relative humidity for 6 days. Each test unit was then assessed visually for insect mortality.
在250 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：1、4、15、70、78、81、83、147、178、213、214、221、228、231和233。 Of the compounds of formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 1, 4, 15, 70, 78, 81, 83, 147, 178, 213, 214, 221, 228, 231 and 233.
測試Dtest D
為了藉由接觸和/或內吸手段評估對桃蚜的防治，測試單元由內部具有12至15天齡蘿蔔植株的小開口容器組成。在化合物施加之前，藉由將從培養植株上切下的一片葉上的30-40隻蚜蟲放置在測試植株的葉上對每個測試單元進行預侵害（切葉法）。隨著葉片脫水，蚜蟲在測試植株上移動。預侵害後，用一層砂覆蓋測試單元的土壤。To evaluate control of green peach aphid by contact and/or systemic means, the test unit consisted of a small open container with 12 to 15 day old radish plants inside. Prior to compound application, each test unit was pre-infested (cut leaf method) by placing 30-40 aphids on a leaf excised from a cultured plant on a leaf of a test plant. Aphids moved on the test plants as the leaves dehydrated. After pre-infestation, the soil of the test unit was covered with a layer of sand.
如上所述配製測試化合物並以250、50和10 ppm噴霧，重複三次。在將配製的測試化合物進行噴霧後，使每個測試單元乾燥1小時，並且然後將黑色遮蔽蓋放置在頂部上。將測試單元在19°C-21°C和50%-70%相對濕度的生長室中保持6天。然後在視覺上評估每個測試單元的昆蟲死亡率。Test compounds were formulated as above and sprayed at 250, 50 and 10 ppm in triplicate. After spraying the formulated test compound, each test unit was allowed to dry for 1 hour, and then a black masking cap was placed on top. Keep the test units in a growth chamber at 19°C-21°C and 50%-70% relative humidity for 6 days. Each test unit was then assessed visually for insect mortality.
在250 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：1、8、23、24、25、33、37、41、44、51、53、56、59、60、66、68、70、74、77、92、93、95、96、98、99、101、105、109、110、112、115、117、125、127、128、132、135、136、138、139、140、141、142、145、147、163、165、168、170、171、172、177、180、182、186、187、189、192、193、197、199、200、201、204、214、217、218、219、222、223、235、236、240、241、243、247、249、2、27、55、81、83、84、137、167、173、174、190、205、210、211、221、230、231、233、228。 Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 1, 8, 23, 24, 25, 33, 37, 41, 44, 51, 53, 56, 59, 60, 66, 68, 70, 74, 77, 92, 93, 95, 96, 98, 99, 101, 105, 109, 110, 112, 115, 117, 125, 127, 128, 132, 135, 136, 138, 139, 140, 141, 142, 145, 147, 163, 165, 168, 170, 171, 172, 177, 180, 182, 186, 187, 189, 192, 193, 197, 199, 200, 201, 204, 214, 217, 218, 219, 222, 223, 235, 236, 240, 241, 243, 247, 249, 2, 27, 55, 81, 83, 84, 137, 167, 173, 174, 190, 205, 210, 211, 221, 230, 231, 233, 228.
在50 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：2、27、55、81、83、84、137、167、173、174、190、205、210、211、221、230、231、233、228。 Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 2, 27, 55, 81, 83, 84, 137, 167, 173, 174, 190, 205, 210, 211, 221, 230, 231, 233, 228.
在10 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：228。 Of the compounds of Formula 1 tested at 10 ppm, the following resulted in at least 80% mortality: 228.
測試ETest E
為了藉由接觸和/或內吸手段評估對棉蚜的防治，測試單元由內部具有5天齡黃秋葵植株的小開口容器組成。這根據切葉法在一片葉上用30-40隻昆蟲進行預侵害，並且用一層砂覆蓋測試單元的土壤。To evaluate control of cotton aphids by contact and/or systemic means, the test unit consisted of a small open container with 5-day-old okra plants inside. This was preinfested with 30-40 insects on a leaf according to the leaf cut method and the soil of the test unit was covered with a layer of sand.
如上所述配製測試化合物並以250、50和10 ppm噴霧，重複三次。噴霧後，將測試單元維持在19°C和70%相對濕度的生長室中6天。然後在視覺上評估每個測試單元的昆蟲死亡率。Test compounds were formulated as above and sprayed at 250, 50 and 10 ppm in triplicate. After spraying, the test units were maintained in a growth chamber at 19°C and 70% relative humidity for 6 days. Each test unit was then assessed visually for insect mortality.
在250 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：4、8、11、14、21、22、29、30、31、35、36、40、43、45、48、50、51、56、57、63、69、72、73、74、92、94、100、101、102、103、105、106、115、116、117、121、122、126、129、132、141、142、147、163、164、165、179、183、185、188、200、204、207、217、218、219、222、223、230、241、2、5、10、12、15、16、17、23、24、25、27、32、34、37、41、42、44、52、55、59、60、66、67、68、70、77、81、83、84、93、95、96、97、98、109、110、112、120、124、125、127、128、140、148、167、171、173、174、176、177、181、182、184、186、187、189、190、192、193、197、201、202、206、211、213、215、216、231、233、243、137、205、210、214、221和228。 Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 4, 8, 11, 14, 21, 22, 29, 30, 31, 35, 36, 40, 43, 45, 48, 50, 51, 56, 57, 63, 69, 72, 73, 74, 92, 94, 100, 101, 102, 103, 105, 106, 115, 116, 117, 121, 122, 126, 129, 132, 141, 142, 147, 163, 164, 165, 179, 183, 185, 188, 200, 204, 207, 217, 218, 219, 222, 223, 230, 241, 2, 5, 10, 12, 15, 16, 17, 23, 24, 25, 27, 32, 34, 37, 41, 42, 44, 52, 55, 59, 60, 66, 67, 68, 70, 77, 81, 83, 84, 93, 95, 96, 97, 98, 109, 110, 112, 120, 124, 125, 127, 128, 140, 148, 167, 171, 173, 174, 176, 177, 181, 182, 184, 186, 187, 189, 190, 192, 193, 197, 201, 202, 206, 211, 213, 215, 216, 231, 233, 243, 137, 205, 210, 214, 221, and 228.
在50 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：2、5、10、12、15、16、17、23、24、25、27、32、34、37、41、42、44、52、55、59、60、66、67、68、70、77、81、83、84、93、95、96、97、98、109、110、112、120、124、125、127、128、140、148、167、171、173、174、176、177、181、182、184、186、187、189、190、192、193、197、201、202、206、211、213、215、216、231、233、243、137、205、210、214、221和228。 Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 2, 5, 10, 12, 15, 16, 17, 23, 24, 25, 27, 32, 34, 37, 41, 42, 44, 52, 55, 59, 60, 66, 67, 68, 70, 77, 81, 83, 84, 93, 95, 96, 97, 98, 109, 110, 112, 120, 124, 125, 127, 128, 140, 148, 167, 171, 173, 174, 176, 177, 181, 182, 184, 186, 187, 189, 190, 192, 193, 197, 201, 202, 206, 211, 213, 215, 216, 231, 233, 243, 137, 205, 210, 214, 221 and 228.
在10 ppm下所測試的式 1的化合物中，以下導致至少80%的死亡率：137、205、210、214、221和228。 Of the compounds of Formula 1 tested at 10 ppm, the following resulted in at least 80% mortality: 137, 205, 210, 214, 221 and 228.
測試FTest F
為了藉由接觸和/或內吸手段評估對銀葉粉虱的防治，每個測試單元由內部具有5至7天齡大豆植株的小開口容器組成。這藉由將測試單元放置在含有成年粉虱的籠子中以便在葉上產卵而進行預侵害。用氣流式噴嘴將成蟲從植株上去除，並將測試單元封蓋。然後將測試單元在噴霧前儲存2至3天。To evaluate control of whitefly by contact and/or systemic means, each test unit consisted of a small open container with 5 to 7 day old soybean plants inside. This was pre-infested by placing test units in cages containing adult whiteflies to lay eggs on leaves. Adults were removed from the plants with air-flow nozzles and the test cells were capped. The test units were then stored for 2 to 3 days before spraying.
如上所述配製測試化合物並以250、50和10 ppm噴霧，重複三次。噴霧後，將測試單元維持在23°C和70%相對濕度的生長室中12天。然後在視覺上評估每個測試單元的昆蟲死亡率。Test compounds were formulated as above and sprayed at 250, 50 and 10 ppm in triplicate. After spraying, the test units were maintained in a growth chamber at 23°C and 70% relative humidity for 12 days. Each test unit was then assessed visually for insect mortality.
在250 ppm下所測試的式 1的化合物中，以下導致至少50%的死亡率：23、51、55、84、117、127、128、129、140、167、190、228、201、214和117。 Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 50% mortality: 23, 51, 55, 84, 117, 127, 128, 129, 140, 167, 190, 228, 201, 214 and 117.
在50 ppm下所測試的式 1的化合物中，以下導致至少50%的死亡率：201、214和117。 Of the compounds of formula 1 tested at 50 ppm the following resulted in at least 50% mortality: 201 , 214 and 117.
在10 ppm下所測試的式 1的化合物中，以下導致至少50%的死亡率：177。 Of the compounds of Formula 1 tested at 10 ppm, the following resulted in at least 50% mortality: 177.
測試GTest G
為了藉由接觸和/或內吸手段評估對西花薊馬的防治，每個測試單元由內部具有5至7天齡大豆（Soleil bean）植株的小開口容器組成。In order to assess control of Thrips occidentalis by contact and/or systemic means, each test unit consisted of a small open container with 5- to 7-day-old Soleil bean plants inside.
如上所述配製測試化合物並以250 ppm噴霧，重複三次。噴霧後，使測試單元乾燥1小時，並且然後將22至27隻成年薊馬加入到每個單元中，然後蓋上遮蔽蓋。將測試單元在25°C和45%-55%相對濕度下保持7天。然後在視覺上評估每個測試單元的植株損害和昆蟲死亡率。Test compounds were formulated as above and sprayed at 250 ppm in triplicate. After spraying, the test units were allowed to dry for 1 hour, and then 22 to 27 adult thrips were added to each unit and then covered with a shelter. The test units were kept at 25°C and 45%-55% relative humidity for 7 days. Each test unit was then visually assessed for plant damage and insect mortality.
在250 ppm下所測試的式 1的化合物中，以下提供了非常好至優異的防治功效水平（20%或更小的取食損害）：142、178、181、182、195、223和234。 Of the compounds of Formula 1 tested at 250 ppm, the following provided very good to excellent levels of control efficacy (20% or less feeding damage): 142, 178, 181 , 182, 195, 223 and 234.
為了比較，對於類似的3-氧雜二環[3.1.0]己烷化合物（索引表X1所示），以及類似的2-硫雜二環[3.1.0]己烷和二環[3.1.0]己烷化合物（以下索引表X2所示），在測試A至H中沒有觀察到在250 ppm下的明顯活性。For comparison, for the analogous 3-oxabicyclo[3.1.0]hexane compound (shown in Index Table X1), and the analogous 2-thiabicyclo[3.1.0]hexane and bicyclo[3.1. 0] hexane compounds (shown in Index Table X2 below), no appreciable activity at 250 ppm was observed in Tests A to H.
索引表X1
索引表X2
無none
無none
無none
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| US2891855A (en) | 1954-08-16 | 1959-06-23 | Geigy Ag J R | Compositions and methods for influencing the growth of plants |
| US3235361A (en) | 1962-10-29 | 1966-02-15 | Du Pont | Method for the control of undesirable vegetation |
| US3060084A (en) | 1961-06-09 | 1962-10-23 | Du Pont | Improved homogeneous, readily dispersed, pesticidal concentrate |
| US3299566A (en) | 1964-06-01 | 1967-01-24 | Olin Mathieson | Water soluble film containing agricultural chemicals |
| US3309192A (en) | 1964-12-02 | 1967-03-14 | Du Pont | Method of controlling seedling weed grasses |
| US4144050A (en) | 1969-02-05 | 1979-03-13 | Hoechst Aktiengesellschaft | Micro granules for pesticides and process for their manufacture |
| US3920442A (en) | 1972-09-18 | 1975-11-18 | Du Pont | Water-dispersible pesticide aggregates |
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| DE3246493A1 (en) | 1982-12-16 | 1984-06-20 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING WATER-DISPERSIBLE GRANULES |
| US5180587A (en) | 1988-06-28 | 1993-01-19 | E. I. Du Pont De Nemours And Company | Tablet formulations of pesticides |
| DE69033861T2 (en) | 1989-08-30 | 2002-06-06 | Kynoch Agrochemicals Proprieta | Manufacture of a dosing agent |
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