JPS636041B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an antimicrobial agent containing a novel quinoline carboxylic acid derivative as an active ingredient. The quinoline carboxylic acid derivative that is the active ingredient of the present invention is a new compound that has not been described in any literature, and has the general formula [In the formula, R ¹ and R ² each represent a lower alkyl group, and R ³ represents a halogen atom. ] These are quinoline carboxylic acid derivatives and salts thereof. The above-mentioned quinolinecarboxylic acid derivatives are useful as active ingredients of antimicrobial agents for medical and agricultural and horticultural purposes. In the above general formula (1), examples of the lower alkyl group represented by R ¹ and R ² include straight chain or branched alkyl groups having 1 to 4 carbon atoms,
Specific examples include methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl groups.
Further, specific examples of the halogen atom represented by R ³ include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, and the like. Representative compounds of the present invention are listed below. Γ1-ethyl-7-chloro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid Γ1,8-diethyl-7-chloro-4-oxo-
1-ethyl-7-fluoro-8-methyl-4-1,4-dihydroquinoline-3-carboxylate
Γ1-methyl-7-chloro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate Γ1-ethyl-7-chloro-8- Isopropyl
4-oxo-1,4-dihydroquinoline-3-
Carboxylic acid Γ1,8-dimethyl-7-bromo-4-oxo-
1,4-dihydroquinoline-3-carboxylic acid A particularly preferred compound in the present invention is 1-ethyl-
7-chloro-8-methyl-4-oxo-1,4-
Dihydroquinoline-3-carboxylic acid and 1-ethyl-7-fluoro-8-methyl-4-oxo-
1,4-dihydroquinoline-3-carboxylic acid. The quinoline carboxylic acid derivative, which is the active ingredient of the present invention, can be produced by various methods, and the method shown in the following reaction formula can be cited as a typical method. [In the formula, R ¹ , R ² and R ³ are the same as above, R ⁴ and R ⁵ are lower alkyl groups, and X represents a halogen atom] For the reduction of the known nitrobenzene derivative represented by the general formula (2), for example, Examples include a method using a reducing agent and a method using catalytic reduction. When a method using a reducing agent is employed, examples of the reducing agent used include iron-hydrochloric acid, zinc-acetic acid, and ferrous chloride-hydrochloric acid. The amount of the reducing agent to be used is usually equimolar to excess, preferably about 3 to 5 times the molar amount of the compound of general formula (2). The reduction reaction is usually carried out at room temperature to 150°C, preferably about 50 to 100°C.
The reaction is generally completed in about 30 minutes to 3 hours. In this way, a compound of general formula (3) is produced. In the reaction between the compound of general formula (3) and the compound of general formula (4), the ratio of the latter to the former is usually at least the same molar amount, preferably about twice the molar amount or more. good. The reaction is usually carried out in the presence of a basic compound without a solvent or in an inert solvent. Specific examples of basic compounds include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, inorganic carbonate compounds such as sodium carbonate, potassium carbonate, potassium hydrogen carbonate, and sodium hydrogen carbonate, pyridine, quinoline, triethylamine, Examples include tertiary amines such as tributylamine. Such a basic compound is usually used in an amount equal to or more than the same molar amount, preferably about 1.1 to 1.5 times the molar amount of the compound of general formula (3). Inert solvents that can be used include lower alcohols such as methanol, ethanol, and isopropanol, ethers such as dioxane, tetrahydrofuran, and diglyme, aromatic hydrocarbons such as benzene and toluene, dimethyl sulfoxide, dimethylformamide, and hexamethylphosphoric triamide. , pyridine, etc.
Among these, aromatic hydrocarbons are preferred. The reaction is usually carried out at room temperature to about 150°C, preferably about 80 to 130°C, and is usually completed in about 0.5 to 6 hours. In this way, a compound of general formula (5) is produced. The reaction between the compound of general formula (5) and the compound of general formula (6) can be carried out without a solvent or in a solvent such as methanol, ethanol, isopropanol, acetonitrile, dimethylformamide, dimethyl sulfoxide, hexamethylphosphoramide, etc., preferably without a solvent. It will be held in The ratio of compound (6) to compound (5) to be used is usually at least equimolar, preferably an equimolar amount in the reaction without a solvent, and preferably about 1.1 to 1.5 times the molar amount in the reaction in a solvent. It is better. The reaction temperature is usually about room temperature to 150℃, preferably about 100 to 130℃
The reaction is usually completed in about 0.5 to 6 hours, and the compound represented by the general formula (7) can be easily obtained. The cyclization reaction of the compound (7) thus obtained can be carried out according to various conventionally known cyclization reactions. Examples include a heating method, a cyclization method using an acidic substance such as phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, concentrated sulfuric acid, and polyphosphoric acid. When employing the cyclization method by heating, a solvent such as high-boiling hydrocarbons and high-boiling ethers such as tetralin, diphenyl ether, diethylene glycol dimethyl ether, etc. is used, and usually about 100 to
Heating conditions of 250°C, preferably about 150-200°C can be employed. When employing a cyclization method using an acidic substance, it is used in an equimolar amount to a large excess, preferably about 10 to 20 times the amount of compound (7), and usually at about 100 to 150°C.
The reaction time may be approximately 0.5 to 6 hours. In this way, a compound of general formula (8) is produced. The hydrolysis reaction of compound (8) obtained by the above cyclization reaction can be carried out using a basic compound such as sodium hydroxide, potassium hydroxide, or barium hydroxide, a mineral acid such as sulfuric acid, hydrochloric acid, or nitric acid, or acetic acid. , in the presence of conventional catalysts such as organic acids such as aromatic sulfonic acids. The reaction is generally carried out using water, methanol, ethanol, isopropanol, acetone,
It is carried out in common solvents such as methyl ethyl ketone, dioxane, ethylene glycol, acetic acid, etc. The reaction temperature is usually room temperature to 200℃, preferably about 50 to 150℃.
It is ℃. In this way, the compound of the present invention represented by general formula (1) can be easily obtained. The present invention includes both acid addition salts and carboxylic acid salts of the quinoline carboxylic acid of general formula (1) obtained above. The acid used to form the acid addition salt may be any pharmacologically or agrochemically acceptable organic or inorganic acid, including, for example, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, phosphoric acid, etc. and organic acids such as acetic acid, oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, malic acid, mandelic acid, ethanesulfonic acid, and P-tosylic acid. The basic compound used to form the carboxylic acid salt may be any pharmacologically or agriculturally acceptable basic compound, such as sodium hydroxide, potassium hydroxide, calcium hydroxide,
Examples include inorganic basic compounds such as aluminum hydroxide and sodium hydrogen carbonate. The compound of the present invention thus produced can be easily isolated and purified by conventional separation means after the completion of the above reaction steps. Examples of the separation means include solvent extraction, dilution, precipitation, recrystallization, column chromatography, and preparative thin layer chromatography. The antimicrobial agent of the present invention containing the compound represented by general formula (1) as an active ingredient has low toxicity and excellent antimicrobial activity. The antimicrobial agent of the present invention is useful for preventing and treating diseases of animals and agricultural and horticultural crops caused by bacteria, fungi, molds, and the like. Examples of animals include mammals including humans, birds, and fish.
The antimicrobial agent of the present invention is also useful for sterilizing and disinfecting medical instruments, etc. Furthermore, when crop damage is expected due to bacteria, mold, etc. during storage or transportation of agricultural and horticultural crops, it is necessary to use antimicrobial agents in advance. The damage can be prevented by applying it to crops by spraying, spraying, coating, etc. Therefore, the antimicrobial agent of the present invention is useful as an antimicrobial agent for medical and agricultural and horticultural purposes. The antimicrobial agent of the present invention is effective against various bacteria, fungi, molds, and the like. As for bacteria, it is effective against both gram-positive and gram-negative bacteria, and specific examples include Pseudomonas, Xanthomonas, Pseudomonadaceae, Erwinia,
Enterobacteriaceae such as Escherichia, Klebsiella, Serratia, Proteus, Salmonella, and Shigella, and microscopic bacteria such as Staphylococcus. Micrococcaceae, Streptococcus, and other Streptococccaceae can be mentioned.
Among these, the antimicrobial agent of the present invention shows excellent activity against Ervina, Xanthomonas, Pseudomonas and Streptococcus, and particularly shows extremely excellent activity against Ervina and Xanthomonas. Examples of fungi that cause mycosis in animals include Cryptococcus neoformans, Coccidioides immites, Candida albicans, and Aspergillus fumigatus.
etc. can be mentioned. Examples of molds that cause fungal diseases of agricultural and horticultural crops include Pyricularia oryzae, Helminthosporium oryzae, and Helminthosporium.
sigmoideum), Phytophthora Phytophthora
melonis), Phytophthora Phytophthora
infestans), Colletotrichum anthracnose (Colletotrichum
lagenarium), cotton anthracnose fungus (Colletotrichum)
indicum), Sclerotinia
sclerotiorum), melon vine blight fungus (Mycosphaerella melonis), pea spot blight fungus (Mycosphaerella phaseolicola), and tomato ring spot fungus (Alternaria solani). The antimicrobial agent of the present invention is useful for the prevention and treatment of bacteriosis and vacuum disease in animals and agricultural and horticultural crops. Bacterial diseases of agricultural and horticultural crops include vegetable soft rot, rice leaf blight, rice sheath blight, peach leaf blight, citrus canker disease, solanaceous plant bacterial wilt, tomato bacterial wilt, tomato wilt, Watermelon vine split disease, cucumber spot bacterial disease, etc., and examples of fungal diseases include rice blast disease, rice sesame leaf blight, cucumber late blight, cucumber gray blight, cucurbit anthracnose, eggplant sclerotium, melon vine blight,
Examples include tomato round strangle disease. The antimicrobial agent of the present invention exhibits an extremely superior effect on vegetable soft rot compared to conventional agents. When the antimicrobial agent of the present invention is used for medical purposes, it exhibits superior effects compared to antibacterial agents containing nalidixic acid conventionally used in this field, as evidenced by, for example, antibacterial test 1 described later. Furthermore, when the antimicrobial agent of the present invention is used for agricultural and horticultural purposes, it exhibits superior effects compared to conventional antibacterial disinfectants containing streptomycin, as is clear from, for example, antibacterial test 3 described later. When the antimicrobial agent of the present invention is used for medical purposes, it is usually in the form of a pharmaceutical composition together with a medical pharmaceutical carrier. As carriers, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, etc., which are commonly used to prepare drugs according to the usage form, can be used. I can give an example. As the dosage unit form of the antimicrobial agent, various forms can be selected depending on the therapeutic purpose, and representative examples include tablets, pills, powders, solutions, suspensions, emulsions,
Examples include granules, capsules, suppositories, injections (solutions, suspensions, etc.), ointments, and the like. When forming tablets, a wide variety of carriers conventionally known in this field can be used, such as lactose, sucrose, sodium chloride, glucose solution, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc. Excipients, water, ethanol, propanol,
Simple syrup, glucose, starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, binder such as polyvinylpyrrolidone, dry starch, sodium alginate, agar powder, laminaria powder, sodium bicarbonate, calcium carbonate, twine, Disintegrants such as sodium lauryl sulfate, stearic acid monoglyceride, starch, and lactose; disintegration inhibitors such as sucrose, stearin, cocoa butter, and hydrogenated oil;
Absorption enhancers such as quaternary ammonium bases and sodium lauryl sulfate, humectants such as glycerin and starch, adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicic acid, purified talc,
Examples include lubricants such as stearate, boric acid powder, and polyethylene glycol. When forming into a pill form, a wide variety of carriers conventionally known in this field can be used, such as excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin, and talc, powdered gum arabic, Examples include binders such as tragacanth powder, gelatin, and ethanol, and disintegrants such as laminaria and agar. Furthermore, the tablets can be made into conventionally coated tablets, such as sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, or multilayer tablets, if necessary. When forming into suppository form,
A wide variety of conventionally known carriers can be used, such as polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semi-synthetic glycerides, and the like. When prepared as injections, solutions and suspensions are preferably sterile and isotonic with blood, and when formed into the form of solutions, emulsions and suspensions, diluents known in the art are used. All commonly used substances can be used, such as water, ethyl alcohol, propylene glycol,
Examples include ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol, and sorbitan ester. In this case, the antimicrobial agent may contain a sufficient amount of salt, glucose, or glycerin to prepare an isotonic solution, and may also contain conventional solubilizing agents, buffers, soothing agents, preservatives, etc. may be contained. Furthermore, the antimicrobial agent of the present invention may contain coloring agents, preservatives, perfumes, flavoring agents, sweeteners, etc., and other pharmaceuticals as necessary. When forming into a paste, cream or gel form, a wide variety of diluents conventionally known in this field can be used, such as white petrolatum, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite and the like. The amount of the active ingredient compound to be contained in the medical antimicrobial agent of the present invention is not particularly limited and can be appropriately selected within a wide range, but it is usually about 1 to 70% by weight based on the total composition. There are no particular restrictions on the use of the above antimicrobial agents, and they can be administered in a manner appropriate for various forms. For example, in the case of tablets, pills, solutions, suspensions, emulsions, granules, and capsules, it is administered orally, and in the case of injections, it is administered intravenously alone or mixed with normal replenishing fluids such as glucose and amino acids. If necessary, it can be administered alone intramuscularly, intradermally, subcutaneously, or intraperitoneally, and in the case of suppositories, it can be administered rectally,
It is also applied as an ointment. The dosage of the medical antimicrobial agent of the present invention is appropriately selected depending on the purpose of use, symptoms, etc., and usually the compound of the present invention is administered at a dose of about 10 mg to 5 g/body per day.
It may be administered in ~4 doses. When using the antimicrobial agent of the present invention for agricultural and horticultural purposes, suitable agricultural and horticultural preparation carriers,
For example, using solid carriers, liquid carriers, suspending agents, spreading agents, etc., granules, powders, dispersants, wettable powders, tablets,
It can be prepared in any form such as oil, spray, or atomizer. The carriers used include clay, kaolin, bentonite, talc, acid clay, diatomaceous earth,
Calcium carbonate, nitrocellulose, starch,
Examples include gum arabic, carbon dioxide, freon, water, benzene, kerosene, alcohol, acetone, xylene, methylnaphthalene, cyclohexanone, and animal and plant fatty acid esters. Examples of suspending agents, spreading agents, etc. include common surfactants such as soaps, sulfuric acid esters of higher alcohols, alkyl sulfonates, quaternary ammonium salts, and polyalkylene oxides. The amount of the active ingredient compound in the agricultural and horticultural antimicrobial agent of the present invention prepared as described above can be determined as appropriate depending on its usage form. For example, in the form of dispersants and wettable powders, it is preferably in the range of about 0.1 to 90% by weight, and in the form of powders and oils, it is preferably in the range of about 0.1 to 10% by weight. Appropriate. When using the agricultural and horticultural antimicrobial agent of the present invention, it can be applied to areas requiring an antimicrobial effect by spraying, spraying, coating, etc. in the same manner as known agricultural and horticultural antimicrobial agents. The amount to be applied can be determined as appropriate depending on the desired effect. For example, the amount of the antimicrobial agent for agricultural and horticultural use of the present invention is usually about 0.1 to 10 kg, preferably about 0.1 to 1 kg per hectare, and of course this will depend on the degree of damage caused by the plants and their diseases. It can be increased or decreased as appropriate. It can also be used in combination with, for example, other antimicrobial agents, insecticides or herbicides, fertilizer substances, soil conditioners, etc. Examples of the production of the active ingredient compound of the present invention are listed below as reference examples, and further formulation examples of the antimicrobial agent of the present invention are listed as examples. Reference Example 1 Synthesis of 2-methyl-3-chloroaniline 29 g of 2-chloro-6-nitrotoluene is added to a mixture of 150 g of stannous chloride and 200 ml of concentrated hydrochloric acid under ice cooling. The solution is then heated at 100°C for 1 hour to obtain white crystals. Take the obtained crystals and add 400ml of water
ml and 50 ml of 40% NaOH and extracted with 500 ml of chloroform. After washing the extract with 400 ml of water, the chloroform layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. By distilling the residue, 23 g of 2-methyl-3-chloroaniline, a fraction of 115 DEG -116 DEG C./10 mmHg, is obtained. Reference Example 2 Synthesis of N-ethyl-2-methyl-3-chloroaniline 14 g of 2-methyl-3-chloroaniline obtained in Reference Example 1 was dissolved in 100 ml of benzene, 12 g of triethylamine was added thereto, 13 g of ethyl bromide was added, and the mixture was refluxed with benzene. Let it react for 3 hours. After the reaction, return to room temperature, add 200 ml of water, and shake. The benzene layer is separated, dried over anhydrous magnesium sulfate, and concentrated. By distilling the residue to 125°~126°C/10mmHg
12 g of N-ethyl-2-methyl-3-chloroaniline, which is a fraction of , is obtained. Reference Example 3 Synthesis of 1-ethyl-7-chloro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid N-ethyl-2-methyl-3-chloroaniline
10g and 15g of diethyl ethoxymethylene malonate
Heat and react at 110°C for 30 minutes. Next, 50g of phosphoric acid
Add polyphosphoric acid (PPA) obtained from 50 g of phosphorus pentoxide and react at 140°C for 40 minutes. After the reaction, the mixture is poured into 600g of water and ice, and crystals precipitate out.
After removing the precipitated crystals, add 10% sodium hydroxide solution and reflux for 1 hour. After refluxing, the mixture is treated with activated carbon and adjusted to pH 2 with concentrated hydrochloric acid to precipitate pale yellow crystals.
Recrystallized from dimethylformamide to give white needle-like crystals of 1-ethyl-7-chloro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.
Get 11g. mp 221-222℃ Reference example 4 1-ethyl-7-fluoro-8-methyl-4-
Synthesis of oxo-1,4-dihydroquinoline-3-carboxylic acid. 9 g of N-ethyl-2-methyl-3-fluoro-aniline and diethyl ethoxymethylene malonate
Heat and react 15g at 110°C for 30 minutes. then phosphoric acid
Add polyphosphoric acid (PAA) obtained from 50 g of phosphorus pentoxide and 50 g of phosphorus pentoxide, and react at 140°C for 40 minutes. After the reaction, the mixture is poured into 600g of water and ice, and crystals precipitate out.
After removing the precipitated crystals, add 10% sodium hydroxide solution and reflux for 1 hour. After refluxing, the mixture is treated with activated carbon and adjusted to pH 2 with concentrated hydrochloric acid to precipitate pale yellow crystals.
Recrystallization from dimethylformamide gave 10 g of 1-ethyl-7-fluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid in the form of white needles. mp 245-246℃ Example 1 Compound obtained in Reference Example 3 200 mg Glucose 250 mg Distilled water for injection Appropriate amount Total volume 5 ml Dissolve the compound of the present invention and glucose in distilled water for injection, and then inject into a 5 ml ampoule. After purging with nitrogen, autoclaving is performed at 121°C for 15 minutes to obtain an injection having the above composition. Example 2 Compound obtained in Reference Example 3 100g Abysiel [trade name: manufactured by Asahi Kasei Corporation] 40g Cornstarch 30g Magnesium stearate 2g TC-5 (trade name: manufactured by Shin-Etsu Chemical Co., Ltd., hydroxypropyl methylcellulose) 10g Polyethylene glycol -6000 3g Castor oil 40g Methanol 40g The compound of the present invention, Apiciel, cornstarch and magnesium stearate are mixed and polished, and then tableted using a kinematic machine with a sugar coating radius of 10mm. TC the obtained tablets
-5. A film coated tablet having the above composition is produced by coating with a film coating agent consisting of polyethylene glycol-6000, castor oil and methanol. Example 3 Compound obtained in Reference Example 3 2g Purified lanolin 5g White beeswax 5g White petrolatum 88g Total amount 100g White beeswax was heated to become liquid, and then the compound of the present invention, purified lanolin and white petrolatum were added and heated until it became liquid. After warming, the mixture is stirred until it begins to solidify to obtain an ointment having the above composition. Example 4 20g of sodium salt of the compound obtained in Reference Example 3 980g of talc The compound of the present invention and talc are mixed and polished to obtain a powder. Example 5 Compound obtained in Reference Example 3 200g White carbon 20g Sodium lignin sulfonate 20g Polyoxyethylene alkyl ether 40g Clay 720g The above compounds were mixed and polished to obtain a wettable powder. Example 6 Compound obtained in Reference Example 3 100g Diatomaceous earth 210g Talc 200g Sodium alkyl sulfate 90g The above compounds are mixed and polished to obtain a wettable powder. Example 7 Compound obtained in Reference Example 3 100g Talc 380g Clay 370g Bentonite 100g Sodium alkyl sulfate 50g The above compounds were mixed and polished, and then granulated using a granulator to obtain granules. <Antibacterial Test 1> The active ingredient compound of the present invention, 1-ethyl-6-fluoro-7-chloro-4-quinolone-3-carboxylic acid (described in claim 2 of JP-A-54-14978) compound) and 1-ethyl-1.4-
The antibacterial activity of dihydro-7-methyl-4-oxo-1,8-naphthylidene-3-carboxylic acid (nalidixic acid, control compound) against various bacteria was determined by the agar dilution plate method. The obtained minimum growth-inhibiting concentrations of bacteria are shown in Table 1 below. Each type of bacteria was adjusted to 1 x 10 ⁸ bacteria/ml (OD660mμ, 0.13-0.14) and 1 x 10 ⁶ bacteria/ml. <Test compound> Compound 1 1-ethyl-7-(1-piperazinyl)
-8-Methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid compound 2 1-ethyl-7-chloro-8-methyl-4-oxo-1,4-dihydroquinoline-3
-Carboxylic acid compound 3 1-ethyl-6-fluoro-7-chloro-4-quinolone-3-carboxylic acid

[Table] <Antibacterial test 2> Prepare a 2% solution of the active ingredient compound of the present invention in acetone, dilute it with water to a specified concentration, place 1 ml of the solution at each concentration in a Petri dish, and place it on 9 ml of potato dextrose agar medium ( (PDA medium) to prepare agar plates containing various concentrations of each of the above test compounds. Use a cork borer with a diameter of 10 mm to punch out the tips of the bacterial cavities of the test bacteria that have been cultured in PDA medium in advance to create bacterial discs, and place them on each agar plate prepared above with the bacterial plaque side down. place The presence or absence of fungal growth was observed with the naked eye after 2 days.
The minimum inhibitory concentration (ppm) that completely inhibits the growth of fungi is shown in Table 2 below for each test fungus. The test bacteria in each table are as follows. Test bacteria A...Bacterium causing vegetable soft rot B...Bacterium causing rice white leaf blight C...Bacterium causing peach green leaf blight D...Bacterium causing citrus canker E...Bacterium causing tomato bacterial wilt F...Bacterium causing cucumber spot G...Bacterium causing rice rootworm H ...Rice and sesame leaf blight fungus I...Cucurbit late blight fungus J...Cucurbit gray blight fungus K...Cucurbit anthracnose fungus L...Eggplant sclerotium fungus M...Melon vine blight fungus N...Tomato ring strangle fungus

[Table] <Antibacterial test 3> Make a radish disc with a diameter of 2 cm and a height of 1 cm.
Injury to the center. A radish disc is immersed in a chemical solution adjusted to a predetermined concentration for one hour, and then air-dried.
A suspension of soft rot fungi (approximately 10 ⁸ /ml) is inoculated onto the injured part of a 10 μ radish disc and kept in a moist room at 28°C. Investigate disease onset after 24 hours. The disease index is determined as follows. Disease area rate Disease index 0 0 0< ≦1/3 1 1/3< ≦2/3 2 >2/3 3

[Table] (Strept 〓

Claims (1)

[Claims] 1. General formula [In the formula, R ¹ and R ² each represent a lower alkyl group, and R ³ represents a halogen atom. ] An antimicrobial agent containing a quinoline carboxylic acid derivative or a salt thereof as an active ingredient.