JPS63284152A - 4-substituted benzylamine derivative, its production and use - Google Patents

Abstract

NEW MATERIAL:A compound of formula I [R1, R2, R3 are H, alkyl, halogenated alkyl; R4 is alkyl; R5 is formula II (R6 is H, alkyl, alkoxy), formula II] and its acid adducts. EXAMPLE:N-Methyl-N-[4-(1-methyl-1-methoxyethylbenzyl]-1-naphthaleneamine. USE:Antimycotic for medical purposes and fungicide for industrial purposes. They are useful against a variety of fungi including fungi parasitic on animals and causing deterioration of industrial materials and products. PREPARATION:The reaction of a compound of formula IV with another compound of formula V gives a benzylamine derivative of formula I. The compound of formula I manifests high therapeutic effect by both local and oral administration.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to general formula (1) [wherein R,, I! ! and R each represent a hydrogen atom, an alkyl group or a halogenated alkyl group, R4 represents an alkyl group, and R represents the group (II-a) an alkyl group, an alkoxy group or a halogen atom. ] The present invention relates to a benzylamine derivative represented by the following formula or an acid addition salt thereof, an antifungal agent for humans or animals, and an industrial disinfectant, which are characterized by containing these as an active ingredient.

[Prior art]

In recent years, research and development of antibiotics such as cephalosporin derivatives has progressed rapidly, and drugs effective against infection by Durham-positive or Durham-negative pathogenic bacteria are being developed and used one after another.

On the other hand, such broad-spectrum antibiotics or immunosuppressants,
With the advent of drugs such as adrenal corticosteroids that significantly reduce human resistance to fungal infections, intractable mycoses are on the rise.

For example, Aspergillus fua+igatus
, 5porothrixschenckii, Cr
Although deep-seated mycoses caused by fungi such as Yptococcus neoforg+ans have become a problem, there are very few effective drugs against them.

Antifungal agents used for deep-seated mycoses include antibiotics typified by griseofulvin, which are used as internal medicines. However, since griseofulvin also acts bacteriostatically, treatment requires a long period of time. May be carcinogenic if administered in large doses over long periods of time. Further Can
It has many drawbacks such as not being effective against dida and other yeasts. Furthermore, the current situation is that even for skin fungal diseases such as whiteheads, it takes a long time for complete treatment with commercially available topical preparations.

Therefore, there is a strong demand for the development of antifungal agents that are highly safe, that is, have few side effects (and that exhibit excellent therapeutic effects against various fungal diseases either by local or oral administration).

In industrial disinfectants, non-metallic disinfectants have appeared to replace inorganic or organic compounds of precious metals, but their effectiveness is limited to certain types of fungi, or the scope of use is limited. The mold effect is not sufficient and often cannot prevent contamination or deterioration of industrial materials or products.

For example, benzimidazole compounds, which are said to be the best among non-metallic fungicides, are found in paints, pastes, wood and bamboo products, textiles, etc., causing deterioration of their properties such as Aspergillus and Penicillium. Penicilliu + *) , ) Lycoderma (
The agar medium dilution method shows very good antibacterial activity against molds such as M. trichoderma. However, molds such as Alternaria and M. It does not show antibacterial activity against molds such as -cor), and does not show antibacterial activity because it does not get stuck in bacteria, and is used in a wide variety of practical situations, such as antibacterial protection for paint films, wall covering materials, and wooden and bamboo products. When used for mold, the practical concentration (1
00-500ρp+w) has the disadvantage that no effect can be expected. Therefore, there is a strong demand for the development of industrial fungicides that are safe and easy to use, exhibiting outstanding effects at practical concentrations.

Compounds similar to the compounds according to the present invention include the general formula (
■) (However, in the formula, X represents a hydrogen atom, a chloro atom, or a methoxy group.) The benzylamine derivative represented by
Organic Chemistry (J, Org.

Chem, ), 12 760 (1947). In this document, various arylmethylamine derivatives were screened for antimalarial activity,
Although the results of the investigation have been reported, the compound represented by the general formula (■) has no activity (no activity is recognized, and there is no description of any other physiological activity including antifungal activity. .

Further, as prior art related to amine compounds, Japanese Patent Publications (A) No. 61-45 and CB) No. 61-2
For example, in prior art (A), the following general formula (■) (■) (wherein R is hydrogen or an alkyl group, R1 is an alkyl group, R1 is hydrogen, a halogen atom or an alkyl group, R4
represents an alkyl group, a cycloalkyl group, a halogenated alkyl group, or a halogen atom, R2 represents hydrogen, an alkyl group, an alkoxy group, a halogen atom, a nitro group, or a hydroxyl group, respectively, and the bonding position of the substituted aminomethyl side chain to the naphthalene ring is 1st or 2nd place. ) and its acid addition salts have been disclosed, and the usefulness of these compounds as antifungal agents has been demonstrated through in vitro antifungal tests (tested bacteria were only genus A. Shown by therapeutic trials. However, there is no mention of its usefulness as an industrial fungicide. The same applies to prior art (B).

Regarding the above-mentioned physiological activity of similar compounds, prior art (A) and (B) only mention antifungal activity. However, in both antifungal and therapeutic tests, the test surface is limited to the genus Shiroishi, and the only treatment method that has been shown is topical administration to the skin surface, so it cannot be said that it has sufficient antifungal activity. Furthermore, there is no mention in any of the prior art of its usefulness in industrial fungicide applications.

[Problem to be solved by the invention]

An object of the present invention is to overcome the drawbacks of conventional drugs as described above, and to provide a pharmaceutical antifungal agent and an industrial fungicide with extremely excellent properties, as well as novel compounds useful therefor. .

In other words, antifungal agents for humans and animals that have few side effects, can be safely used either locally or orally, and have excellent therapeutic effects, as well as antifungal agents that can be used in industrial materials and products and cause contamination. It is an object of the present invention to provide a highly safe industrial fungicide that can completely control frequently used molds for a long period of time.

[Means and effects for solving the problem] In order to solve the above problem, as a result of various studies on a large number of benzylamine derivatives, it was found that 4-substituted henzylamine derivatives and their acid addition salts are effective against animal-parasitic fungi and other industrial materials. It was discovered that it has excellent antibacterial activity and a wide antibacterial spectrum against many fungi that cause product deterioration.

Furthermore, it was discovered that the compound of the present invention exhibits a high therapeutic effect on fungal diseases when administered locally or orally, and also has a high antifungal effect when added to industrial materials and products, and the present invention was completed. Ta.

That is, the present invention relates to the general formula (1) [wherein RI+ Rt and R8 each represent a hydrogen atom, an alkyl group, or a halogenated alkyl group, R4 represents an alkyl group, and Rs represents a group (II-a) alkyl group , an alkoxy group or a halogen atom, ] or an acid addition salt thereof.

The compound of the present invention is a new compound, and has extremely excellent antibacterial activity and a wide antibacterial spectrum against many fungi that cause deterioration of industrial materials and products, including animal-parasitic fungi. It shows a high therapeutic effect on fungal diseases by both local and oral administration, and also has a high antifungal effect when added to industrial materials and products.

Furthermore, the method for producing the compound of the present invention according to the present invention is (a)
General formula (I[[) R, -NH-Ri [wherein, R4
and R2 respectively have the above-mentioned meanings,] is a compound represented by the general formula (IV) R1 [wherein RI+R1 and Rs each have the above-mentioned meanings]. ] or (b) reacting the compound represented by the general formula (V) [wherein Rz, R3, R4 and R2 each have the above-mentioned meanings], or (b) reacting the compound represented by the general formula (Vl). Y-R.

[In the formula, R1 has the above meaning. ] This is a method for producing a benzylamine derivative represented by the general formula (1), which is characterized by reacting a compound represented by the following.

Hereinafter, the manufacturing method according to the present invention will be described in more detail by showing a reaction formula.

H co(III) (TV) (b) R2 (wherein R+-Rt, R, I, Ra and R2 each have the above meanings, X and Y are reactive residues (e.g.)
＼Indicates a rogen atom or an ester residue such as a sulfonyl group or a tosyl group).

Further, the compounds represented by general formulas (IV) and (V) include new compounds, and routes C and D are shown below as an example of the production method.

(XI) (IV)
[In the formula, Rls Rt, R1, R,, R3, X and Y each have the above-mentioned meanings, R is an alkyl group, and xl is]
In other words, in route (a), formula (III) and formula (TV)
In route (b), a compound represented by formula (V)
The compound (1) of the present invention can be obtained by reacting the compound represented by the formula (V[) and the formula (V[)] in an inert solvent in the presence of a basic substance.

Examples of inert solvents include common inert solvents, such as lower alcohols such as methanol and ethanol (mixed with water if necessary), aromatic hydrocarbons such as benzene, toluene, and xylene, chloroform, carbon tetrachloride, Halogenated hydrocarbons such as monochlorobenzene and dichlorobenzene, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, ethers such as diethyl ether, dioxane, and tetrahydrofuran, and aprotons such as dimethylformamide, dimethyl sulfoxide, and dimethyl imidazolidinone. A polar solvent etc. can be used.

Bases include inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium alcoholade, ammonia, trimethylamine, triethylamine, and pyridine. The reaction temperature ranges from 0 °C to the boiling temperature of the reaction mixture, preferably from room temperature to 60 °C, and the reaction time may be long, but is usually 1 to 6 hours. Bye.

The compound of the present invention thus obtained is converted into an acid addition salt by a conventional method, if necessary. Acids that can form such salts include acetic acid, citric acid, tartaric acid, malic acid,
Organic acids such as oxalic acid, fumaric acid, maleic acid, succinic acid, naphthalene-1,5-disulfonic acid, naphthalene-2,7-disulfonic acid, P-)luenesulfonic acid, and hydrohalic acids, sulfuric acid, nitric acid, Examples include inorganic acids such as phosphoric acid.

Furthermore, the present invention provides an antifungal agent for humans or animals containing a benzylamine derivative represented by the general formula (1) or an acid addition salt thereof as an active ingredient, and a benzylamine derivative represented by the general formula (1) or an acid addition salt thereof. A fungicidal agent characterized by administering to an animal in need of treatment an effective amount of an industrial countryicide, a benzylamine derivative represented by general formula H) or a chemotherapeutically acceptable acid addition salt, as an active ingredient. Treatment methods for epidemics or infectious diseases that occur, and the general formula (1
This is a method for controlling fungi and molds, which is characterized by incorporating or treating industrial raw materials or industrial products with a benzylamine derivative represented by the following formula or an acid addition salt thereof.

That is, the compound of the present invention (H) has excellent bactericidal activity against a wide range of fungi including animal-parasitic fungi. Therefore, it can be applied to control attacks on humans, animals, industrial materials and products by a wide variety of fungi. I can do it.

The compound of the present invention can be used as it is in the form of a free base or in the form of a chemically acceptable salt, but it is usually prepared and used as follows depending on each application.

When used as a human or veterinary antifungal agent, the compounds of the invention may be used in admixture with chemotherapeutically acceptable diluents and carriers and optionally other excipients to form tablets or capsules. It can be administered orally or topically in conventional forms such as ointments or creams. These formulations can generally be formulated according to conventional methods for formulation. For adult humans, the dosage is, for example, 100 to 2000 m/day for oral administration.
It may be g.

When used as an industrial disinfectant, the compound of the present invention is usually used in the form of a preparation supported on a carrier, such as an oil solvent, emulsion, paste, powder, wettable powder, aerosol, or the like.

The liquid carrier used in the preparation of the compound of the present invention may be any liquid as long as it does not react with the active ingredient, such as water, alcohols (methanol, ethanol, ethylene glycol, propylene glycol, etc.), ketones (
acetone, methylethylkenine, etc.), ethers (dioxane, tetrahydrofuran, cellosolve, etc.), aliphatic hydrocarbons M (kerosene, gasoline, etc.), aromatic hydrocarbons M (benzene, toluene, xylene, etc.), halogenated hydrocarbons M (chloroform, dichloroethane, etc.), acid amides M (dimethylformamide, etc.), esters M (acetic acid ethyl ester, etc.), organic bases! [(Pyridine etc.), Nitrile M (Acetonitrile etc.) and
Diethylene glycol monomethyl ether, diethylene glycol monomethyl ether, etc. can be used. In addition, inorganic solid carriers such as clay, talc, bentonite, kaolin, and white carbon, and gas carriers such as dimethyl ether and Freon gas can also be used.

If necessary, an ionic or nonionic surfactant, a polymer compound such as vinyl acetate, methyl cellulose, etc. can be used in combination as an auxiliary agent to further enhance the formulation effect. It can also be used in combination or as a mixture with other agricultural chemicals, such as insecticides, acaricides, fungicides, fragrances, or other industrial fungicides and fungicides.

〔Example〕

EXAMPLES The present invention will be explained in more detail below using examples, pruning examples, and test examples, but the scope of the present invention is not limited by these in any way.

First, the manufacturing method of Zero Invention and Invention will be specifically explained with reference to Examples.

Example 1 (Route a) Process for producing N-methyl-N-(4-(1-methyl-1-methoxyethyl)benzylco-1-naphthalenemethylamine.

1.10 g of N-methyl-1-naphthalenemethylamine (
6.4 mmol), potassium carbonate 1.38 g (LOm
mol) and dimethylformamide (15 ml), 1.55 g (6.4 mwol) of 4-(1-methyl-1-methoxyethyl)benzyl bromide was added while stirring.

After reacting at 40°C for 2 hours, the mixture was poured into water and extracted with toluene. After washing with water and drying, toluene was distilled off under reduced pressure to obtain 2.17 g of a residue. This was subjected to silica gel column chromatography (hexane-ethyl acetate (19:1)).
) to obtain 1.57 g (y, 736χ) of the target product.

":" 1.5846 Example 2 Process for producing N-methyl-N-(4-(1-methyl-1-methoxyethyl)-benzyl)-1-naphthalenemethylamine hydrochloride.

0.64 g of the compound obtained in Example 1 (1,9a+mol
) was dissolved in 5 ml of ethyl acetate, and added with 35× concentrated hydrochloric acid
．． When 16ml is added, salt precipitates out. This was filtered and dried to obtain 0.52 g (y, 73.2χ) of the target product.

Melting point: 195-198'C Note that the production example of 4-(1-methyl-1-methoxyethyl)benzyl bromide used in Example 1 was followed by route (c).
An example of this is shown in Reference Example 1.

Reference Example 1 (Route C) (i) Production of 2-(4-methylphenyl)-2-protanol 13.4 g of 4-methylacetophenone was added to a diethyl ether solution of methylmagnesium iodide (0.15 ml) under a nitrogen stream. (0.1 mol) was cooled with water, and then stirred at room temperature for 1 hour. After this, 101 ml of ethyl acetate was added on ice-cooling.
1. Furthermore, 10 liters of saturated ammonium chloride aqueous solution was added dropwise. This was poured into water and extracted with diethyl ether. After washing the ether layer with water and drying, the ether was distilled off and purified using a column to obtain 14.2 g (y, 94.5K) of the desired product.

n:”! 1.5140 +1MRδ +s4’ (ppm); 1.49 (6H,
s), 2.25 (LH, s).

2.31 (3H, s).

7.04 (28, d, J-8Hz) 7.26 (2H, d, J-8Hz) (ii) 2 obtained by method (i) for producing 2-(4-methylphenyl)-2-propyl methyl ether 9.31 g (0,062 sol) of -(4-methylphenyl)-2-propatol and 10.09 g (0,08 sol) of dimethyl sulfuric acid are dissolved in 30 ml of dimethylformamide and stirred. 6 at 0℃ under nitrogen flow
0z oily sodium hydride 2.48g (0,062s+
After adding ol), the temperature was slowly returned to room temperature. When the reaction started, heat was generated, but the mixture was cooled and kept at 40° C. or below, and stirred for an additional 3 hours.

After adding 2 ml of concentrated aqueous ammonia and stirring at room temperature for another 1 hour, the reaction mixture was poured into water, extracted with ethyl acetate, washed with water, dried, and purified by column chromatography to obtain the desired product (5.77).
g (y, 56.7χ) was obtained.

n:'m1.494O NMRδcr5+s" (ppm): 1.47 (61
1,s), 2.32(3H,s).

2.96 (3H, s).

7.07 (2H, d, J-8Hz) 7.20 (2H, d, J-8Hz) (ij) Method for producing 4-(1-methyl-1-methoxyethyl)benzyl bromide.

5.77g of the compound obtained in (ii) (0,035T@
ol) and 6.50 g of N-bromosuccinimide (0,0
37 sol) was added to 50 ml of benzene, then α
, α1-azobisisobutyronitrile was added little by little while stirring under reflux. After completion of the reaction, the reaction solution was poured into a dilute aqueous sodium bicarbonate solution and extracted with benzene.

After washing with water and drying, the product was purified by column chromatography to obtain 5.66 g (y, 66.5χ) of the target product.

n:'-1,5440 Melting point 34.5-36.5°C Example 3 (Route b) N-Methyl-N-(4-(1-methyl-1-ethoxyethyl)benzyl)-1-naphthalenemethylamine manufacturing method.

N-Methyl-N-(4-(1-methyl-1-hydroxyethyl)benzyl)-1-naphthalenemethylamine 0.
6g (1,9vwol), 60χ oily sodium hydride 0.08g (20v++ol), diethyl sulfate 0.29
g (1,9+imol) in dimethylformamide 10■
The reaction mixture was stirred at 80°C for 3 hours and poured into dilute aqueous sodium bicarbonate solution, and extracted with benzene.

The organic layer was washed with water, dried, and benzene was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate (19:1)) to obtain the desired product.
4g (y, 63.2χ) was obtained.

n: @-1.5796 Note that N-methyl-N-[4-(l-
Methyl-1-hydroxyethyl)benzylco-1-naphthalenemethylamine is a new compound, and its production example is shown in Reference Example 2 as an example of route (d).

Reference Example 2 (Route d) (i) N-(4-ethoxycarbonylbenzyl)-N-
Method for producing methyl-1-naphthalenemethylamine 5.32g of N-methyl-1-naphthalenemethylamine (
0,031 mol), potassium carbonate 4.42 g (0,
032 mol) and dimethylformamide 30-1 was added 7.29 g of ethyl 4-bromomethylbenzoate (0.032 mol) and dimethylformamide (30-1
, 030 mol) and stirred at 50° C. for 2 hours. The reaction solution was poured into water and extracted with toluene. The organic layer was washed with water, dried, and purified by column chromatography to obtain 7.32 g (y, 73.2χ) of the desired product.

n”-1,5882 NMR δ basin: (3 (ppm); 1.39 (3H, t,
J-7,0Hz), 2.22(3H,s), 3.64(
2H,s), 3.99(2H,s), 4.39(2H
, q, J-7Hz).

7.3-8.5 (IIH, m) (ii) Process for producing N-methyl-N-(4-(1-methyl-1-hydroxyethyl)benzyl)-1-naphthalenemethylamine Methylmagnesium iodide (0 , 03 mol) in 10 ml of diethyl ether under a nitrogen atmosphere, a solution of 2.5 g (7,5n+nol) of N-(4-ethoxycarbonylbenzyl)-N-methyl-1-naphthalenemethylamine dissolved in 5 ml of diethyl ether was heated to room temperature. After dripping with
Stir at reflux temperature for 30 minutes. Then, under water cooling, 5 ml of ethyl acetate and 10 ml of a saturated ammonium chloride aqueous solution were added, and the reaction solution was poured into water and extracted with diethyl ether. After washing the organic layer with water and drying, the ether was distilled off and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate (4:1)). Objective 1
．． 96g (y, 81.8χ) was obtained.

n”-1,576O NMRδ=:L (ppm); 1.59 (6H
, s), 2.17 (IH, s).

2.21 (38, s), 3.60 (2H, s).

3.95 (2H, s).

7.2 to 8.4 (IIH, +s) Representative examples of the compounds of the present invention synthesized according to the above examples are shown in Table 1 along with physical property values.

Next, the composition according to the present invention will be specifically explained with reference to formulation examples.

Formulation Example 1 Compound 1 of the present invention 20 parts Neugen E
A-878 parts (surfactant manufactured by Daiichi Kogyo Seiyaku ■) Emar 10 (surfactant manufactured by Kao ■) 2 parts water
A suspension agent was obtained by uniformly mixing 70 parts or more.

Formulation Example 2 Compound 3 of the present invention 20 parts Emal 1
0 (Surfactant manufactured by Kao ■) 5 parts Emulgen 92
0 (〃) 5 parts At least 70 parts of clay were ground and mixed uniformly to obtain a wettable powder.

Formulation Example 3 Compound 5 of the present invention 40 parts Discsol HP-1587 parts (surfactant manufactured by Daiichi Kogyo Seiyaku ■) Ami-) 105 (surfactant manufactured by Kao ■) 13 parts Xylene 40 parts or more were mixed uniformly. , an emulsion was obtained.

Test Example 1 Antibacterial activity evaluation test (1) Antibacterial activity was evaluated by agar dilution. That is, the compound of the present invention was added to a Bareishi glucose agar medium at a concentration of 0.8~
The mixture was mixed at a graded concentration of 100 pp-, stirred well, and then poured into a Petri dish to form an agar plate. After the agar had solidified, a pure culture of the test bacteria was inoculated and evaluated after culturing at 25°C for 7 days. The minimum concentration of the test compound contained in the medium at which the inoculated bacteria do not grow is called the minimum inhibitory concentration (MIC).
pps) in Table 2.

The test bacteria are as follows.

Bacterial name Bacterial name abbreviation Aspergillus niger A, n (Asp
ergillus niger) Benicillium citrinum P, c (Penicillium
citrinu+*) Cephalosporium
C, sp (Cephalosporium s
p,) Gibberella fujikuroi G, f
(Gibberella fujikuroi) Talatosporium cladosporoidus C0C (C1ados
portu+m cladospoloides) Chaetomium globosum C, g (Chae
tomium globosum) Alternaria Alternaria A, a (Alternaria
As a comparison compound, 2, which has particularly stable effects, was selected from benzimidazole compounds, which are considered to be the best non-metallic fungicides currently used as industrial fungicides. -(4-thiazolyl)-benzimidazole (hereinafter abbreviated as TBZ) was used.

It is clear from Table 2 that the compound of the present invention has strong antibacterial activity against a wide variety of fungi that degrade industrial materials and products and cause great losses. Aspergillus niger and Penicillium citrinum, which cause problems in a wide range of areas, including pipes, oils, telecommunications equipment, and electrical equipment.
It also has extremely high antibacterial activity against C. citrinum. In addition, TBZ used as a comparative compound showed no antibacterial activity at all in Alternaria alternata (Alte
It also showed high antibacterial activity against rnaria alternata).

Test Example 2 Antibacterial activity evaluation test (2) Antibacterial activity was evaluated by the paper disc method. In advance, extract malt and yeast, prepare a plate of agar medium (pH 6,0), and prepare a spore suspension for 1.3.4 of the following test bacteria, 2.
Place 0.2 ml of a bacterial cell suspension (concentration: 4 x 10'5 pores or cells/ml) into a medium plate and spread with a spreader. A sterilized paper disk (8-diameter) is placed on top of it, 20 ml of acetone or aqueous solutions of various concentrations of each test compound are poured into this paper disk and incubated at 28°C.

After 5 days, the size of the inhibition circle was measured and the minimum inhibitory concentration MIC (
pps) was determined. The results are shown in Table 3.

Test bacterium name: Aspergillus fumigatus
HUT 2034 Sporothrix 5chenckii
TIMM 0959 Cryptococcus neoformans
) TIMM 0354 Candida parapsilosis
TIMM 0287 Trichophyton mentag
IPO5929 Microsporum gypssum
IFO8231The comparison compound was commercially available canestin (which is currently widely used as an antibacterial agent).
Clotrimazole) was used.

It is clear from Table 3 that the compounds of the present invention exhibit strong antibacterial activity against fungi that parasitize humans and animals and cause fungal diseases. In particular, the dermatophyte Trichophyton mentagrophytes
r+tagrophytes) and Microsporum gypseum.
The antibacterial activity against Clotrimazole
Aspergillus fuumigatus (Asp.
ergillus fu-sigatus) Sporo-thrix 5ch
It is clear that it also exhibits very high antibacterial activity against various fungi such as C. er+ckii).

Furthermore, the compound of the present invention also shows antifungal activity in an in vivo test using experimental dermatomycosis in guinea pigs. In this test, the compound of the present invention was topically administered to the skin surface every day for 2 weeks starting 5 days after infection with trichophytonosis. The invention compound was dissolved in polyethylene glycol) or administered orally at concentrations of 0.01-5% for topical administration and 2-70 mg/Kg for oral administration in guinea pig tests.

Therefore, when the compounds of the present invention are used as antifungal agents for humans or animals, they can be administered locally or orally. For human adults, the dosage may be, for example, 100 to 200°-g per day orally.

Test Example 3 (Mold resistance test for emulsion paint) The test method was based on the JIS-Z-2911r mold resistance test method. That is, 0.1x and 0.2x of each drug (20% formulation product) was added to acrylic emulsion paint (Vini Deluxe No. 300, manufactured by Kansai Paint Co., Ltd.) and mixed well. 0.00% of the drug-added paint was applied to the front and back sides of a filter paper with a diameter of 3c11. Ig was applied and air-dried. This filter paper was placed on an agar medium having the following composition and inoculated with a mixed spore suspension by spraying. The cells were cultured for two weeks at a temperature of 28° C. and a humidity of 95%.

The results indicate the degree of mold growth on the sample surface as follows:
It is indicated in 5 stages of +, +++, and the indication (1, 2, 3) according to the JIS standard mold resistance indication method is also written.

11.No mold growth is observed on the sample surface ±, extremely small amount of mold growth is observed on a part of the sample surface+, mold growth is clearly observed on a portion of the sample surface below about 173 cm ++, Mold growth is observed on the sample surface of approximately 173 or more +++1++ Mold growth is observed on the entire surface of the sample 3, Mycelia growth is not observed on the sample surface 2, Mycelia growth is observed on the sample surface The area of the part does not exceed 173 of the total area 1, the area of the growing part of mycelia observed on the sample surface exceeds 173 of the total area of the medium; water 1000a + 1. 40g glucose, 1 peptone
0g agar 25g Aureobasidum ullulans Table 4
Emulgin paint mold-proof test results Umbrella TBZ's generosity TBZ Kabe lactic acid seal Noigen EA-875# ■-Industrial Pharmaceutical ■ Interface W po silk water 15〃〃
[Effects of the Invention] As is clear from the above explanation, the compound of the present invention has excellent antibacterial activity against many fungi that cause deterioration of industrial materials and products, including animal-parasitic fungi. can be effectively used to prevent many disorders caused by

As described above, the compound of the present invention, which can be effectively used in the fields of pharmaceutical antifungal agents and industrial fungicides, is a highly useful drug.

Claims (7)

[Claims] (1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1, R_2 and R_3 each represent a hydrogen atom, an alkyl group or a halogenated alkyl group, and R_
4 represents an alkyl group, R_5 is a group (II-a) ▲ formula,
There are chemical formulas, tables, etc.▼ (However, R_6 in the formula represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom.)
Or (II-b) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is shown. ] A benzylamine derivative or an acid addition salt thereof. (2) (a) General formula (III) R_4-NH-R_5 [In the formula, R_4 represents an alkyl group, R_5 represents a group (II-a)
▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_6 in the formula
represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom. )
Or (II-b) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is shown. ] The compound represented by the general formula (IV) ▲Mathematical formula, chemical formula, table, etc.▼(IV) [In the formula, R_1, R_2 and R_3 each represent a hydrogen atom, an alkyl group or a halogenated alkyl group. [In the formula, R_2, R_3, R_4 and R_5 each have the above meanings. . ] The compound represented by general formula (VI) Y-R_1 [wherein,
R_1 indicates the above meaning. [In the formula, R_1, R_2, R_3, R_4 and R_5 each have the above meanings. show. ] A method for producing a benzylamine derivative represented by: (3) The second claim characterized in that the reactive residues X and Y are halogen atoms or ester residues.
Manufacturing method described in section. (4) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1, R_2 and R_3 each represent a hydrogen atom, an alkyl group or a halogenated alkyl group, and R_
4 represents an alkyl group, R_5 is a group (II-a) ▲ formula,
There are chemical formulas, tables, etc.▼ (However, R_6 in the formula represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom.)
Or (II-b) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is shown. ] An antifungal agent for humans or animals containing a benzylamine derivative or an acid addition salt thereof as an active ingredient. (5) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1, R_2 and R_3 each represent a hydrogen atom, an alkyl group or a halogenated alkyl group, and R_
4 represents an alkyl group, R_5 is a group (II-a) ▲ formula,
There are chemical formulas, tables, etc.▼ (However, R_6 in the formula represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom.)
Or (II-b) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is shown. ] An industrial disinfectant containing a benzylamine derivative or its acid addition salt as an active ingredient. (6) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1, R_2 and R_3 each represent a hydrogen atom, an alkyl group or a halogenated alkyl group, and R_
4 represents an alkyl group, R_5 is a group (II-a) ▲ formula,
There are chemical formulas, tables, etc.▼ (However, R_6 in the formula represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom.)
Or (II-b) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is shown. ] A method for treating epidemics or infectious diseases caused by fungi, which comprises administering to an animal in need of treatment an effective amount of a benzylamine derivative or a chemotherapeutically acceptable acid addition salt represented by: (7) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1, R_2 and R_3 each represent a hydrogen atom, an alkyl group or a halogenated alkyl group, and R_
4 represents an alkyl group, R_5 is a group (II-a) ▲ formula,
There are chemical formulas, tables, etc.▼ (However, R_6 in the formula represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom.)
Or (II-b) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is shown. ] A method for controlling fungi and molds, which comprises incorporating or treating an effective amount of a benzylamine derivative or an acid addition salt thereof into an industrial raw material or an industrial product.