Aromatic ester compound containing pyridine ring as well as preparation method and application of aromatic ester compound

Abstract

The invention provides an aromatic ester compound containing a pyridine ring and a preparation method and application thereof, and particularly relates to a compound shown in a formula (I) or pharmaceutically acceptable salt thereof and application of the compound or the pharmaceutically acceptable salt in preparation of bactericides in the agronomic field or the horticultural field. # imgabs0 #, the compound of formula (I) shows excellent biological activity on various germs in the agronomic field or horticultural field, and an excellent effect can be obtained at a relatively low dosage.

Description

Technical Field

[0001] The invention belongs to the technical field of agronomic or horticultural fungicides, and specifically relates to an aromatic ester compound containing a pyridine ring, a preparation method and application thereof. Background Art

[0002] In the agricultural field, with the promotion of straw return and no-till technology, plant residues are not handled well in production, and many pathogens survive the winter and summer through plants, resulting in a large number of plant pathogens remaining in the soil. In addition, as the problem of disease resistance becomes increasingly serious, farmers need to increase the amount of pesticides used, but this will increase drug residues, causing pollution and burden on the environment. Therefore, it is necessary to develop new varieties of pesticides with high effectiveness.

[0003] Patent document WO2014006945 discloses the aromatic ester compound CK1 (compound number 46) shown below:

[0004]

[0005] Patent document JP2016056117 discloses the aromatic ester compound CK2 (compound number 150) shown below:

[0006]

[0007] Patent document JP2016056100 discloses the aromatic ester compound CK3 (compound number 125) shown below:

[0008]

[0009] However, the biological activity of the above compounds still needs to be further improved. In order to find a fungicide with better performance, the inventors conducted in-depth research. Summary of the invention

[0010] In order to solve the above technical problems, the present invention provides an aromatic ester compound containing a pyridine ring or a pharmaceutically acceptable salt thereof as shown in the following formula (I):

[0011]

[0012] Wherein, R1 is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl or NR A R B ;

[0013] R A or R B are the same or different and are independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C6 alkyl;

[0014] R2 is selected from hydrogen or C1-C6 alkyl;

[0015] Alternatively, R1 and R2 are connected together to form

[0016] R3 is selected from hydrogen or C1-C6 alkyl;

[0017] R4 is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C6 alkyl;

[0018] R5 is selected from hydrogen or C1-C6 alkyl;

[0019] Alternatively, R4 and R5 are connected together to form

[0020] R6 and R7 are the same or different and are independently selected from hydrogen or C1-C6 alkyl;

[0021] Provided that the pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof is not the following compound:

[0022]

[0023] According to an embodiment of the present invention, R1 is selected from hydrogen, C1-C4 alkyl (e.g. methyl, ethyl or propyl), C3-C6 cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), C3-C6 cycloalkyl C1-C3 alkyl (e.g. -methylcyclopropyl, -methylcyclobutyl, -methylcyclopentyl or -methylcyclohexyl) or NR A R B [e.g. NH2, NHC1-C4alkyl, N(C1-C4alkyl)2, -NHcyclopropyl, -NHcyclobutyl, -NHcyclopentyl or -NHcyclohexyl];

[0024] R A or R B are the same or different and are independently selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C4 alkyl;

[0025] R2 is selected from hydrogen or C1-C4 alkyl;

[0026] Alternatively, R1 and R2 are connected together to form

[0027] R3 is selected from hydrogen or C1-C4 alkyl;

[0028] R4 is selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl) or C3-C6 cycloalkylC1-C4 alkyl (e.g. -methylcyclopropyl, -methylcyclobutyl, -methylcyclopentyl or -methylcyclohexyl);

[0029] R5 is selected from hydrogen or C1-C4 alkyl;

[0030] Alternatively, R4 and R5 are connected together to form

[0031] R6 and R7 are the same or different and are independently selected from hydrogen or C1-C4 alkyl;

[0032] Provided that the pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof is not the following compound:

[0033]

[0034] According to an embodiment of the present invention, R1 is selected from hydrogen, methyl, ethyl, or NR A R B ; R A or R B are the same or different and are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl,

[0035]

[0036] R2 is selected from hydrogen or methyl;

[0037] Or R1 and R2 are connected together to form R3 is selected from hydrogen or methyl;

[0038] R4 is selected from hydrogen, methyl, ethyl, R5 is selected from hydrogen, methyl; or R4 and R5 are connected together to form R6 and R7 are the same or different and are independently selected from hydrogen or methyl.

[0039] According to an embodiment of the present invention,

[0040] R1 is selected from hydrogen, methyl, ethyl, or NR A R B ;

[0041] R A or R B are the same or different and are independently selected from hydrogen, methyl, ethyl, R2 is selected from hydrogen or methyl;

[0042] R3 is selected from hydrogen or methyl;

[0043] R4 is selected from hydrogen, methyl, ethyl, R5 is selected from hydrogen or methyl;

[0044] R6 and R7 are the same or different and are independently selected from hydrogen or methyl.

[0045] According to an embodiment of the present invention, R1 is selected from methyl, According to an embodiment of the present invention, R2 is selected from hydrogen;

[0046] According to an embodiment of the present invention, R3 is selected from hydrogen;

[0047] According to an embodiment of the present invention, R4 is selected from methyl, ethyl, According to an embodiment of the present invention, R5 is selected from hydrogen;

[0048] According to an embodiment of the present invention, R6, R7 are both selected from hydrogen.

[0049] According to an embodiment of the present invention, the compound of formula (I) is selected from the following compounds or pharmaceutically acceptable salts thereof,

[0050]

[0051] Table 1

[0052]

[0053]

[0054] For the purpose of reducing the length of the specification, the exemplary groups and / or compounds of the present invention are described in the form of the above tables.

[0055] The present invention also provides a method for preparing the compound of formula (I) or a pharmaceutically acceptable salt thereof, comprising:

[0056]

[0057] Wherein, R1, R2, R3, R4, R5, R6, and R7 have the definitions as described above;

[0058] The compound represented by formula (II) reacts with the compound represented by formula (III) to obtain the compound represented by formula (I).

[0059] According to an embodiment of the present invention, compound (II) reacts with compound (III) in the presence of a condensing agent and a base to prepare compound (I). Preferably, the condensing agent is selected from one of N, N'-carbonyldiimidazole (CDI), N, N'-dicyclohexylcarbodiimide (DCC), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI), etc. The base is selected from an organic base and an inorganic base; for example, it can be selected from one, two or more of triethylamine, pyridine, DIEA, DMAP, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium hydride, etc. Preferably, the reaction is carried out in a solvent; the solvent can be selected from one, two or more of toluene, acetonitrile, tetrahydrofuran, etc. Preferably, the reaction temperature is 25°C to 120°C.

[0060] According to an embodiment of the present invention, the method further includes a preparation process of the compound represented by formula (III), comprising:

[0061] 1) reacting a compound represented by formula (V) with a compound represented by formula (VI) to obtain a compound represented by formula (IV);

[0062] 2) The compound represented by formula (IV) is reduced to obtain the compound represented by formula (III);

[0063]

[0064] Wherein, R4, R5, R6, and R7 have the definitions as described above;

[0065] L1 is selected from a leaving group, such as a halogen atom (exemplarily fluorine, chlorine, bromine or iodine).

[0066] According to an embodiment of the present invention, in step 1), the compound shown in (V) reacts with the compound shown in formula (VI) in the presence of a base to prepare compound (IV). Preferably, the base is selected from an organic base and an inorganic base; for example, one, two or more selected from triethylamine, pyridine, DIEA, DMAP, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium hydride, etc. Preferably, the reaction is carried out in a solvent; the solvent may be selected from one, two or more selected from N,N-dimethylformamide, toluene, acetone, acetonitrile, tetrahydrofuran, etc. Preferably, the reaction temperature is 25°C to 150°C.

[0067] According to an embodiment of the present invention, in step 2), compound (IV) is prepared into compound (III) in the presence of a reducing agent (e.g., sodium borohydride or lithium aluminum tetrahydride). Preferably, the reaction is carried out in a solvent; the solvent may be selected from one, two or more of benzene, toluene, tetrahydrofuran, methyltetrahydrofuran, ether, methanol, ethanol, etc. Preferably, the reaction temperature is -30°C to 25°C.

[0068] According to an embodiment of the present invention, the above reaction can be carried out with reference to the method described in patent document WO2014006945 or WO2017126197 or other similar methods.

[0069] The preparation process of the present invention can, depending on the reaction conditions and the selection of starting materials suitable in each case, for example, replace only one substituent with another substituent according to the present invention in a single reaction step, or can replace multiple substituents with other substituents according to the present invention in the same reaction step.

[0070] If the respective compounds are not accessible via the routes described above, they can be prepared by derivatizing other compounds of the formula (I) or by conventionally varying the synthetic routes described.

[0071] The reaction mixture is worked up in a customary manner, for example by mixing with water, phase separation and purification of the crude product by chromatography, for example on aluminum oxide or silica gel.

[0072] According to an embodiment of the present invention, the pharmaceutically acceptable salt of the compound shown in formula (I) can be prepared by a known method. For example, a pharmaceutically acceptable acid addition salt of the compound shown in formula (I) is obtained by suitable acid treatment. The preparation method is as follows: the compound shown in formula (I) is reacted with an acid (organic acid, inorganic acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, malic acid or citric acid, etc.) to obtain a pharmaceutically acceptable salt of the compound shown in formula (I). Preferably, the reaction is carried out in a solvent; preferably, the solvent is selected from water, ether, toluene, etc.

[0073] The above preparation method can obtain an isomer mixture of the compound represented by formula (I). If pure isomers are required, conventional methods such as crystallization or chromatography can be used for separation.

[0074] According to an embodiment of the present invention, the compound represented by formula (I) also includes its isomers, racemates, deuterated compounds and hydrates.

[0075] Unless otherwise stated, all of the above reactions are conveniently carried out at atmospheric pressure or at the native pressure of the particular reaction.

[0076] The present invention also provides the use of the compound represented by the above formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a fungicide, wherein the fungicide is used in the agronomy field (agricultural fungicide) or the horticulture field (horticultural fungicide).

[0077] The present invention also provides the use of at least one of the compounds represented by the above formula (I) or pharmaceutically acceptable salts thereof as a fungicide, wherein the fungicide is used in the agronomy field (agricultural fungicide) or the horticulture field (horticultural fungicide).

[0078] The present invention also provides a composition comprising at least one of the compounds represented by the above formula (I) or pharmaceutically acceptable salts thereof as an active ingredient.

[0079] The present invention also provides use of the composition as a fungicide, which can be used in the agronomic field (agricultural fungicide) or the horticultural field (horticultural fungicide).

[0080] The present invention also provides a method for preventing and controlling pathogens (e.g., plant pathogens) or diseases in the agronomic or horticultural fields, the method comprising applying an effective amount of the compound represented by the above formula (I) or a pharmaceutically acceptable salt thereof or at least one of the compositions to a growth medium of the pathogens or diseases (e.g., plant pathogens).

[0081] The examples of diseases mentioned below are only used to illustrate the present invention, but they are by no means limiting.

[0082] The compound represented by formula (I) or its pharmaceutically acceptable salt or the composition can be used to prevent and control the following diseases or their corresponding pathogens: Oomycete diseases, such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, loofah downy mildew, wax gourd downy mildew, melon downy mildew, cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rape white rust Disease, white rust of cabbage), damping-off (rapeseed damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cotton rot (pepper cotton rot, loofah cotton rot, wax gourd cotton rot), blight (broad bean blight, cucumber blight, pumpkin blight, wax gourd blight, watermelon blight, melon blight, pepper blight, leek blight, garlic blight, cotton blight), late blight (potato late blight, tomato late blight), etc.;Deuteromycin diseases, such as wilt (sweet potato wilt, cotton wilt, sesame wilt, castor wilt, tomato wilt, kidney bean wilt, cucumber wilt, loofah wilt, pumpkin wilt, wax gourd wilt, watermelon wilt, melon wilt, pepper wilt, broad bean wilt, rapeseed wilt, soybean wilt), root rot (pepper root rot, eggplant root rot, kidney bean root rot, cucumber root rot, bitter melon root rot, cotton black root rot, broad bean root rot), damping-off (cotton seedling damping-off, sesame damping-off, pepper damping-off, cucumber damping-off, cabbage damping-off), anthracnose (sorghum anthracnose, cotton anthracnose, hemp anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, mulberry anthracnose Disease, pepper anthracnose, eggplant anthracnose, bean anthracnose, cucumber anthracnose, bitter gourd anthracnose, zucchini anthracnose, wax gourd anthracnose, watermelon anthracnose, melon anthracnose, litchi anthracnose), Verticillium wilt (cotton wilt, sunflower wilt, tomato wilt, pepper wilt, eggplant wilt), black spot (zucchini black spot, wax gourd black spot, melon black spot), gray mold (cotton boll gray mold, hemp gray mold, tomato gray mold, pepper gray mold, kidney bean gray mold, celery gray mold, spinach gray mold, kiwifruit gray mold), brown spot (cotton brown spot, jute brown spot, beet brown spot, peanut brown spot, pepper brown spot, wax gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot Black spot (false black spot of flax, black spot of rape, black spot of sesame, black spot of sunflower, black spot of castor, black spot of tomato, black spot of pepper, black spot of eggplant, black spot of kidney bean, black spot of cucumber, black spot of celery, black rot of carrot, black spot of carrot, black spot of apple, black spot of peanut), spot blight (spot blight of tomato, spot blight of pepper, spot blight of celery), early blight (early blight of tomato, early blight of pepper, early blight of eggplant, early blight of potato, early blight of celery), ring rot (soybean ring rot, sesame ring rot, kidney bean ring rot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem base rot (stem base rot of tomato, vegetable Bean stem base rot), and others (corn round spot, jute waist break disease, rice blast, chestnut black sheath disease, sugarcane eye spot disease, cotton boll Aspergillus disease, peanut crown rot, soybean stem blight, soybean black spot disease, melon large spot disease, peanut web spot disease, tea red leaf spot disease, pepper white star disease, wax gourd leaf spot disease, celery black rot, spinach heart rot, jute leaf mold, jute spot disease, jute stem spot disease, soybean purple spot disease, sesame leaf spot disease, castor gray spot disease, tea brown leaf spot disease, eggplant brown round star disease, kidney bean red spot disease, bitter melon white spot disease, watermelon spot disease, jute blight rot, sunflower root and stem rot disease, kidney bean charcoal rot, soybean target spot disease, eggplant coryneform leaf spot disease, cucumber target spot disease, tomato leaf mold disease, eggplant leaf mold disease, broad bean red spot disease, etc.);Basidiomycete diseases, such as rust (wheat stripe rust, wheat stem rust, wheat leaf rust, flower rust, sunflower rust, sugarcane rust, leek rust, onion rust, chestnut rust, soybean rust), smut (corn silk smut, corn powdery mildew, sorghum silk smut, sorghum loose smut, sorghum hard smut, sorghum column powdery mildew, chestnut kernel smut, sugarcane smut, bean rust) and others (such as wheat sheath blight, rice sheath blight, etc.); Ascomycete diseases, such as powdery mildew (wheat powdery mildew, rape powdery mildew, sesame powdery mildew, Powdery mildew of sunflower, beet, eggplant, pea, loofah, pumpkin, zucchini, wax gourd, melon, grape, broad bean), sclerotinia (flax, rape, soybean, peanut, tobacco, pepper, eggplant, bean, pea, cucumber, bitter melon, wax gourd, watermelon, celery), scab (apple scab, pear scab), etc. ;

[0083] According to an embodiment of the present invention, the compound represented by formula (I) or its pesticide acceptable salt or the composition can be used to prevent and control the following pathogenic bacteria or their corresponding diseases:

[0084] Gram-negative bacteria: Erwinia (causing fire blight of apricot, etc.); Pectobacterium (causing soft rot of cruciferous vegetables, potato black leg, etc.); Dickie's genus (causing sweet potato stem rot, corn bacterial stem rot, rice bacterial basal rot, potato black leg, pear rust, etc.); Pantoea (causing corn bacterial wilt, corn Pantoea leaf spot, red bean bacterial leaf blight, stone fruit tree canker, etc.); Pseudomonas (causing peach canker, pea bacterial Phytophthora, bacterial black spot of crucifer, bacterial leaf spot of tomato, bacterial spot of tomato, bacterial black spot of rape, bacterial angular spot of sesame, bacterial angular spot of cucumber, wildfire of tobacco, bacterial brown spot of corn, bacterial brown spot of corn, bacterial stem blight of broad bean, bacterial spot of soybean, bacterial leaf spot of beet, bacterial pith necrosis of tomato, soft rot of Pseudomonas aeruginosa of ginseng, etc.); Ralstonia (causing various bacterial wilt diseases, etc.); Burkholderia ( The genus Acidovorax (cause bacterial wilt of carnation, onion rot, bacterial ear blight of rice, etc.); the genus Acidovorax (cause fruit spot of melon, brown spot of orchid, brown streak of oat, bacterial leaf spot of konjac, etc.); the genus Xanthomonas (cause bacterial leaf blight of rice, bacterial streak of rice, spot disease of pepper and tomato, scab of pepper and tomato, bacterial black spot of mango, bacterial leaf spot of pepper, bacterial blight of poinsettia, angular spot of cotton, bacterial spot of soybean, black rot of crucifer, wood Potato bacterial wilt, sugarcane gummosis, anthurium bacterial blight, citrus canker, hyacinth yellow rot, peach bacterial punchhole, strawberry angular leaf spot, poplar bacterial canker, etc.); Agrobacterium (causing root cancer in Rosaceae, etc.); Xylem bacteria (causing Pierce's disease in grapes and citrus variegated chlorosis, etc.); Phloemobacter (causing citrus Huanglongbing, etc.); Enterobacter (causing poplar wilt, etc.); Xylophilus (causing bacterial blight in grapes, etc.).

[0085] Gram-positive bacteria: Corynebacterium (causing potato ring rot, bacterial canker of tomatoes, bacterial wilt of alfalfa, internal wilt of corn, bacterial mosaic of wheat, etc.); Streptomyces (causing potato scab, etc.); Brevibacterium (causing bacterial wilt of beans, yellow blister of tulip, bean wilt, etc.); Arthrobacter (causing American holly leaf blight, etc.); Rhodococcus (causing sweet pea banding, etc.); Bacillus (causing Bacillus leaf spot of corn, white leaf streak of wheat, etc.); Russell's bacillus (causing duckgrass honey ear disease, etc.).

[0086] According to an embodiment of the present invention, the compound represented by formula (I) or its pesticide acceptable salt or the composition can be used to prevent and control the following pathogens or their corresponding diseases: rice blast, rice sheath blight, rice false smut, tomato gray mold, peanut root rot, wheat fusarium, yellow fusarium, citrus resin pathogen, potato black mole, rapeseed sclerotinia, false graminearum Fusarium, maize pseudoverticillium, potato infestation, wheat take-all pathogen, and citrus anthracnose.

[0087] To obtain the desired effect, the amount of compound used will vary depending on factors such as the compound used, the crop to be protected, the type of pest, the degree of infestation, climatic conditions, the method of application, and the formulation employed.

[0088] The selection of ingredients for the dosage forms or compositions described herein should be consistent with the physical properties of the active ingredient, the mode of application, and environmental factors such as soil type, moisture and temperature.

[0089] The dosage forms include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspensions), etc., which may be optionally thickened into colloids. The dosage forms also include solids such as dusts, powders, granules, tablets, pills, films, etc., which may be water-dispersible ("wettable") or water-soluble. The active ingredient can be microencapsulated and then made into a suspension or solid dosage form; in addition, the entire dosage form of the active ingredient can also be encapsulated. Encapsulation can control or delay the release of the active ingredient. Sprayable dosage forms can be diluted in a suitable medium, and the spray volume used is about one hundred to several hundred liters per hectare. High-concentration compositions are mainly used as intermediates for further processing.

[0090] Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. Surfactants and recommended applications are listed in McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964. All formulations may contain small amounts of additives to reduce foaming, prevent caking, prevent corrosion, prevent microbial growth, etc., or thickeners to increase viscosity.

[0091] The surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfonated succinates, alkyl sulfates, alkylbenzene sulfonates, organosilanes, N,N-dialkyl taurates, lignin sulfonates, condensates of naphthalene sulfonates with aldehydes, polycarboxylates and polyoxyethylene / polyoxypropylene block copolymers.

[0092] Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silicon dioxide, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate, sodium bicarbonate, sodium sulfate; liquid diluents include, for example, water, N,N-dimethylformamide, dimethyl sulfone, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzene, alkylnaphthalene, olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and cocoa butter, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, dodecanol and tetrahydrofuranol.

[0093] Solutions, including emulsifiable concentrates, can be prepared by simply mixing the components. Dusts and fine powders can be prepared by mixing or grinding, usually in a hammer mill or fluid mill. Suspensions are generally prepared by wet grinding, for example, as described in US 3060084. Granules and pellets are prepared by spraying the active substance onto a freshly prepared granular carrier or by granulation techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, 147-48; Perry's Chemical Engineer's Handbook, 4TH Ed., McGraw-Hill, New York, 1963, 8-57; and WO 9113546. The preparation of pellets is introduced in US 4172714, water dispersible and water soluble granules are prepared by the methods described in US 4144050, US 3920442 and DE 3246493. Tablets are prepared by the methods described in US 5180587, US 5232701 and US 5208030. Films can be prepared by the methods described in GB 2095558 and US 3299566.

[0094] For more information on processing, see U.S. Pat. No. 3,235,361, at col. 6, line 16 to col. 7, line 19, and Examples 10-41; U.S. Pat. No. 3,309,192, at col. 5, line 43 to col. 7, line 62, and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167, and 169-182; U.S. Pat. No. 2,891,855, at col. 3, line 66 to col. 5, line 17, and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York 1961, 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

[0095] Herein, for certain applications of the composition, such as in agriculture, one, two or more other fungicides, insecticides, miticides, herbicides, plant growth regulators or fertilizers may be added to the composition of the present invention, thereby producing additional advantages and effects.

[0096] Definitions and explanations of terms

[0097] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the subject matter of the claims pertains. Unless otherwise indicated, all patents, patent applications, and publications cited herein are incorporated herein by reference in their entirety. If there are multiple definitions of a term herein, the definition in this chapter shall prevail.

[0098] When the numerical ranges in the specification and claims of this application can only be "integers", it should be understood that the two endpoints of the range and each integer in the range are recorded. For example, "1-5" should be understood as recording each integer of 1, 2, 3, 4, and 5.

[0099] In some groups, "-" or The ligation site is indicated.

[0100] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0101] The term "pharmaceutically acceptable salt" as used herein refers to a salt that retains the biological effectiveness of the free acid and free base of the specified compound and has no adverse effects in biology or other aspects. The compounds of the present application also include pharmaceutically acceptable salts, such as nitrates, hydrochlorides, sulfates or phosphates. Pharmaceutically acceptable salts refer to the form in which the basic group in the parent compound is converted into a salt. Pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic groups such as amine (amino) groups. The pharmaceutically acceptable salts of the present application can be synthesized from the parent compound, that is, the basic group in the parent compound reacts with 1-4 equivalents of acid in a solvent system.

[0102] The term "C1-C6 alkyl" means straight and branched alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, etc. or isomers thereof. In particular, the group is a straight or branched saturated monovalent hydrocarbon group having 1, 2, 3 or 4 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, tert-butyl or isomers thereof.

[0103] The above definition of the term "alkyl", such as "C1-C6 alkyl", is also applicable to other terms containing "C1-C6 alkyl", for example, the term "C3-C6 cycloalkyl C1-C6 alkyl" and the like.

[0104] The term "C3-C6 cycloalkyl" refers to a saturated or partially unsaturated monocyclic cyclic hydrocarbon radical, which may contain 3 to 6 carbon atoms, such as 3, 4, 5, 6 carbon atoms. The carbocycle may be a saturated cycloalkyl or may optionally contain one, two or more double bonds and / or triple bonds on its ring, thereby forming a so-called cycloalkenyl or cycloalkynyl radical. For example, the non-limiting examples of monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl.

[0105] Beneficial Effects

[0106] The compounds of formula (I) of the present invention show good activity against various pathogens in the fields of agronomy and horticulture. Moreover, these compounds can achieve good control effects at very low dosages, and their control effects are better than those of existing compounds, so they can be used to prepare fungicides.

[0107] In addition, the compound of the present invention has simple preparation steps and high yield, and thus has good application prospects. DETAILED DESCRIPTION

[0108] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0109] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0110] The following method was used for LC-MS analysis:

[0111] Chromatographic column: Agilent ZORBAX SB-C18 150 mm × 4.6 mm, 5 μm (inner diameter);

[0112] Detection wavelength: 254nm;

[0113] Flow rate: 0.8 mL / min;

[0114] Column temperature: 30°C;

[0115] Gradient elution conditions:

[0116] Table 2

[0117]

[0118] Synthesis Example

[0119] Example 1: 4-((6-methylpyridin-2-yl)oxy)-2-amino-6-methylnicotinic acid benzyl ester (Compound 1)

[0120]

[0121] Step 1: Preparation of 4-((6-methylpyridin-2-yl)oxy)benzaldehyde (Intermediate 1)

[0122] At room temperature, 3.72g (30mmol) 4-fluorobenzaldehyde and 3.27g (30mmol) 2-hydroxy-6-methylpyridine were dissolved in 60mL N,N-dimethylformamide. 12.44g (90mmol) potassium carbonate was added to the above mixture, the temperature was raised to 110°C, and stirred for 12h. The mixture was distilled under reduced pressure, 50ml water was added to the residue, and ethyl acetate (2×30mL) was used for extraction. The organic layers were combined, washed with 20mL saturated brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and 4.86g of the product was obtained by column chromatography (eluent: a mixture of ethyl acetate and petroleum ether (1:3)).

[0123] Step 2: Preparation of (4-((6-methylpyridin-2-yl)oxy)phenyl)methanol (Intermediate 2)

[0124] At room temperature, 4.0 g (18.8 mmol) of 4-((6-methylpyridin-2-yl)oxy)benzaldehyde (intermediate 1) was dissolved in methanol (30 ml). Under stirring at 25 °C, 1.42 g (37.5 mmol) of sodium borohydride was added in batches, and the reaction solution was stirred for 12 h. The reaction solution was slowly added to water (30 ml) to quench, filtered, and the filtrate was extracted with ethyl acetate (3×30 mL). The organic layers were combined, washed with saturated brine (20 mL), and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and column chromatography (eluent: a mixture of ethyl acetate and petroleum ether (1:3)) was performed to obtain 3.64 g of the product.

[0125] Step 3: Preparation of 4-((6-methylpyridin-2-yl)oxy)-2-amino-6-methylnicotinic acid benzyl ester (Compound 1)

[0126] At room temperature, 2.15g (10mmol) (4-((6-methylpyridin-2-yl)oxy)phenyl)methanol (intermediate 2) and 1.83g (12mmol) 2-amino-6-methylnicotinic acid (intermediate 3) were dissolved in dichloromethane (30ml), 2.88g (15mmol) EDCI and 2.44g (20mmol) DMAP were added, and the reaction solution was heated to 50°C and stirred for 3h. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to obtain a crude product, and column chromatography (eluent: a mixture of ethyl acetate and petroleum ether (1:3)) was performed to obtain 2.76g of the product.

[0127] LC / MS[M+H] + =350.15, [M+Na] + =372.06, [M+K] + =388.09. 1 H NMR (400MHz,CDCl3):δ

[0128] 7.99(d,1H),7.73(t,1H),7.49(d,2H),7.11-7.16(m,4H),7.00(d,1H),6.79(d,1H),6.50(d,1H),5.30(s,2H),2.31(s,6H).

[0129] Example 2

[0130] Other compounds of the present invention were synthesized by referring to the above method.

[0131] The structural characterization data of some compounds of formula (I) are shown in Table 3 below:

[0132] Table 3

[0133]

[0134]

[0135]

[0136]

[0137]

[0138]

[0139] Formulation Examples

[0140] In the following examples, all percentages are by weight and all dosage forms are prepared by conventional methods.

[0141] Embodiment 3:

[0142] This example uses the compound obtained in the above example to prepare a wettable powder, specifically using the following raw material composition for preparation:

[0143] Compound 1 60.0%, dodecylphenol polyethoxyglycol ether 4.0%, sodium lignin sulfonate 5.0%, sodium aluminosilicate 6.0%, montmorillonite (calcined) 25.0%.

[0144] Embodiment 4:

[0145] In this example, the compound obtained in the above example is used to prepare granules, and the raw material composition is specifically used for preparation:

[0146] Compound 2 10.0%, other components are sodium dodecyl sulfate 2%, calcium lignin sulfonate 6%, potassium chloride 10%, polydimethylsiloxane 1%, and soluble starch is used to make up to 100%.

[0147] Embodiment 5:

[0148] In this embodiment, the compound obtained in the above embodiment is used to prepare extruded pellets, and the raw material composition is specifically used for preparation:

[0149] Compound 3 25.0%, anhydrous calcium sulfate 10.0%, crude calcium lignin sulfonate 5.0%, sodium alkyl naphthalene sulfonate 1.0%, calcium / magnesium bentonite 59.0%.

[0150] Embodiment 6:

[0151] This example uses the compound obtained in the above example to prepare emulsifiable concentrate, and specifically adopts the following raw material composition for preparation:

[0152] Compound 4 25.0%, solvent 150 60%, PEG 400 5%, Rhodacal 70 / B 3%, Rhodameen RAM / 77%.

[0153] Embodiment:7:

[0154] In this example, the compound obtained in the above example is used to prepare an aqueous suspension, and the raw material composition is specifically used for preparation:

[0155] Compound 10 30.0%, POE polystyrene phenyl ether sulfate 5.0%, xanthan gum 0.5%, polyethylene glycol 5%, triethanolamine 1%, sorbitol 0.5%, and water to 100.0%.

[0156] Biological activity assay

[0157] The compound of the present invention exhibits good inhibitory activity against various pathogens in the fields of agronomy and horticulture.

[0158] Embodiment 8:

[0159] 1. Determination of bactericidal activity

[0160] The compounds of the present invention were tested for their in vitro antibacterial activity against various fungal diseases of plants. The results of the fungicidal activity tests are shown in the following examples.

[0161] The test method is as follows: Dissolve the sample of the compound to be tested with a suitable solvent (the type of solvent is acetone, methanol, DMSO, etc., and is selected according to its solubility in the sample) to prepare a test solution of the required concentration. In an ultra-clean working environment, add the test solution to the culture medium, mix well and pour into a 9 cm culture dish, then inoculate the pathogen hyphae into the center of the culture medium, and place the treated culture plate in a constant temperature incubator for culture. After 3 days of culture, conduct an investigation, visually observe the germination or growth of the pathogen propagules, and evaluate the antibacterial activity of the compound (expressed as "inhibition rate") based on the germination or growth of the blank and solvent controls.

[0162] The inhibition rate was calculated as follows: mycelium growth inhibition rate (inhibition rate) (%) = [(control colony diameter - bacterial cake diameter) - (treated colony diameter - bacterial cake diameter)] / (control colony diameter - bacterial cake diameter) × 100. The control colony refers to the colony after solvent treatment, and the bacterial cake diameter is 7 mm.

[0163] (1) The test results of the in vitro antibacterial activity of the compounds against rice blast fungus (expressed as inhibition rate) are as follows:

[0164] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on rice blast fungus are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0165] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on rice blast fungus are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 29, 32, and 33.

[0166] (2) The test results of the in vitro antibacterial activity of the compounds against Rhizoctonia solani (expressed as inhibition rate) are as follows:

[0167] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on rice sheath blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0168] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on rice sheath blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 32, and 33.

[0169] (3) The test results of the in vitro antibacterial activity of the compounds against U.S. smut pathogen (expressed as inhibition rate) are as follows:

[0170] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on rice false smut fungus are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0171] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on rice false smut fungus are: 1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 32, and 33.

[0172] (4) The test results of the in vitro antibacterial activity of the compounds against Botrytis cinerea (expressed as inhibition rate) are as follows:

[0173] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on tomato gray mold are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0174] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on tomato gray mold are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 29, 30, 31, 32, 33.

[0175] (5) The test results of the in vitro antibacterial activity of the compounds against peanut root rot pathogens (expressed as inhibition rate) are as follows:

[0176] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on peanut root rot pathogens are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0177] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on peanut root rot pathogens are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 23, 24, 25, 26, 32, and 33.

[0178] (6) The test results of in vitro antibacterial activity of some compounds against wheat fusarium sphaeroides (expressed as inhibition rate) are as follows:

[0179] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on wheat fusarium rust are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0180] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on wheat fusarium rust are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 24, 25, 28, 29, 31, 32, 33.

[0181] (7) The test results of the in vitro antibacterial activity of some compounds against yellow scurf virus (expressed as inhibition rate) are as follows:

[0182] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on yellow sickle pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0183] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% against yellow sickle pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 31, 32, 33.

[0184] (8) The test results of in vitro antibacterial activity (expressed as inhibition rate) of some compounds against citrus resinosis pathogen are as follows:

[0185] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% against citrus resin pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0186] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% against citrus resin pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 31, 32, 33.

[0187] (9) The test results of the in vitro antibacterial activity of the compound against potato black mole pathogen (expressed as inhibition rate) are as follows:

[0188] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on potato black mole pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0189] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on potato black mole pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 30, 32, 33.

[0190] (10) The test results of the in vitro antibacterial activity of the compounds against Sclerotinia sclerotiorum (expressed as inhibition rate) are as follows:

[0191] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on rapeseed sclerotinia pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0192] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on rapeseed sclerotinia pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33.

[0193] (11) The test results of the in vitro antibacterial activity of the compound against Fusarium graminearum (expressed as inhibition rate) are as follows:

[0194] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on the pseudograminearum Fusarium are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0195] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on the pseudograminearum Fusarium are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 30, 33.

[0196] (12) The test results of the in vitro antibacterial activity of the compounds against Pseudomonas aeruginosa (expressed as inhibition rate) are as follows:

[0197] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on Pseudomonas aeruginosa are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0198] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on Pseudomonas aeruginosa of corn are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33.

[0199] (13) The test results of the in vitro antibacterial activity of the compound against potato late blight (expressed as inhibition rate) are as follows:

[0200] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on potato late blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0201] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on potato late blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 28, 29, 30, 31, 32, 33.

[0202] (14) The test results of the in vitro antibacterial activity of the compound against wheat take-all pathogen (expressed as inhibition rate) are as follows:

[0203] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on wheat take-all pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33.

[0204] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on wheat take-all pathogen are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 31, 32, 33.

[0205] (15) The test results of the in vitro antibacterial activity of the compound against citrus anthracnose (expressed as inhibition rate) are as follows:

[0206] At a dosage of 10 ppm, the compounds with an inhibition rate of more than 80% on citrus anthracnose are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, and 31.

[0207] At a dosage of 1 ppm, the compounds with an inhibition rate of more than 80% on citrus anthracnose are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 33.

[0208] 2. Test results of exemplary compounds and control agents

[0209] This example conducted an activity comparison test of the exemplary example compounds and the control compounds (the control compound CK1 is the compound No. 46 in the patent document WO2014006945, the control compound CK2 is the compound No. 150 in the patent document JP2016056117, and the control compound CK3 is the compound No. 125 in the patent document JP2016056100). The results of the inhibition rate test on different pathogens are shown in Table 4 below.

[0210] The test conditions of the comparative test are: carried out according to the above-mentioned test method of inhibition rate.

[0211]

[0212] Table 4

[0213]

[0214]

[0215] In addition to the compounds listed in the above table, the pathogen control activities of other exemplary compounds of the present invention are better than those of the control agents. Therefore, the compounds of formula (I) of the present invention show good activity against a variety of pathogens in the agricultural field.

[0216] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof, in, R1 is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl or NR A R B ; R A or R B are the same or different and are independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C6 alkyl; R2 is selected from hydrogen or C1-C6 alkyl; Alternatively, R1 and R2 are connected together to form R3 is selected from hydrogen or C1-C6 alkyl; R4 is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C6 alkyl; R5 is selected from hydrogen or C1-C6 alkyl; Alternatively, R4 and R5 are connected together to form R6 and R7 are the same or different and are independently selected from hydrogen or C1-C6 alkyl; Provided that the pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof is not the following compound:

2. The pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein: R1 is selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C3 alkyl or NR A R B ; R A or R B are the same or different and are independently selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C4 alkyl; R2 is selected from hydrogen or C1-C4 alkyl; Alternatively, R1 and R2 are connected together to form R3 is selected from hydrogen or C1-C4 alkyl; R4 is selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylC1-C4 alkyl; R5 is selected from hydrogen or C1-C4 alkyl; Alternatively, R4 and R5 are connected together to form R6 and R7 are the same or different and are independently selected from hydrogen or C1-C4 alkyl; Provided that the pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof is not the following compound:

3. The pyridine ring-containing aromatic ester compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein: R1 is selected from hydrogen, methyl, ethyl, or NR A R B ; R A or R B are the same or different and are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, R2 is selected from hydrogen or methyl; Or R1 and R2 are connected together to form R3 is selected from hydrogen or methyl; R4 is selected from hydrogen, methyl, ethyl, R5 is selected from hydrogen, methyl; or R4 and R5 are connected together to form R6 and R7 are the same or different and are independently selected from hydrogen or methyl.

4. The pyridine ring-containing aromatic ester compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein: The pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof is selected from the following compounds or a pharmaceutically acceptable salt thereof:

5. A method for preparing a pyridine ring-containing aromatic ester compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein: include: Wherein, R1, R2, R3, R4, R5, R6, and R7 have the definitions as described above; The compound represented by formula (II) reacts with the compound represented by formula (III) to obtain the pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

6. Use of the pyridine ring-containing aromatic ester compound represented by formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a bactericide according to any one of claims 1 to 4, wherein: The fungicides are used in the agronomic field (agricultural fungicides) or in the horticultural field (horticultural fungicides).

7. Use of at least one of the pyridine ring-containing aromatic ester compounds of formula (I) or pharmaceutically acceptable salts thereof as a fungicide, wherein the fungicide is used in the agronomy field (agricultural fungicide) or the horticulture field (horticultural fungicide).

8. A composition comprising as an active ingredient at least one of the pyridine ring-containing aromatic ester compounds represented by formula (I) according to any one of claims 1 to 4 or pharmaceutically acceptable salts thereof.

9. Use of the composition according to claim 8 as a fungicide, which can be used in the agronomic field (agricultural fungicide) or the horticultural field (horticultural fungicide).

10. A method for preventing and controlling pathogens (e.g., plant pathogens) or diseases in the field of agriculture or horticulture, the method comprising applying an effective amount of at least one of the pyridine ring-containing aromatic ester compound of formula (I) according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof or the composition according to claim 8 to a growth medium of the pathogens or diseases (e.g., plant pathogens); Preferably, the pyridine ring-containing aromatic ester compound represented by formula (I) according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof or the composition according to claim 8 is used to prevent and control the following pathogens or their corresponding diseases: rice blast, rice sheath blight, rice false smut, tomato gray mold, peanut root rot, wheat fusarium, yellow fusarium, citrus resinosis, potato black mole, rapeseed sclerotinia, false graminearum, maize pseudoverticillium, potato infestation, wheat take-all, and citrus anthracnose.

Images