JPH0768186B2 - Amine compound and antifungal agent containing the same as active ingredient - Google Patents

Description

Detailed Description of the Invention [0001] The present invention is of the general formula (I): [0002] [Chemical 9] (In the formula, R¹Is the formula: [0003] [Chemical 10] (In the formula,X is a hydrogen atom, a halogen atom or a methyl group
R) ² Represents a hydrogen atom or a methyl group,
R ³ Represents a methyl group or an ethyl group, R ^Five Is the formula: [0004] [Chemical 11] Indicates.However, R¹Has the formula: [0005] [Chemical 12] R is a group represented by ² ButHydrogen atom, R³Is meth
Ru basisAndExcluding cases. ) Amine compound represented by
Or an acid addition salt thereof, and an antifungal agent containing it as an active ingredient
Regarding fungal agents. [0006] Prior Art / Problems to be Solved by the Invention General formula
R in (I)¹Has the formula: [0007] [Chemical 13] (In the formula, R⁶Is a hydrogen atom, halogen atom, or alkyl group.
Or represents a nitro group), R is²But water
An atom or an alkyl group, R³Is an alkyl group
Ri, R ^FiveHas the formula: [0008] [Chemical 14] (In the formula, R⁷Represents an alkyl group or a cycloalkyl group
A group represented byRuRegarding the compound, Japanese Patent Application No. 5
Filed already in 9-118636. The object of the present invention is to have useful antifungal activity
Novel amine compound with
It is to provide a fungicide. [0010] [Means for Solving the Problems]
As a result of the above, a new amine having useful antifungal activity
The compound was discovered and the present invention was completed. That is, the present invention has the general formula (I): [0012] [Chemical 15] (In the formula, R ¹ Is the formula: [0013] [Chemical 16] (In the formula, X represents a hydrogen atom, a halogen atom or a methyl group.
R) ² Represents a hydrogen atom or a methyl group,
R ³ Represents a methyl group or an ethyl group, R ^Five Is the formula: [0014] [Chemical 17] Indicates.However, R¹Has the formula: [0015] [Chemical 18] R is a group represented by ² ButHydrogen atom, R³Is meth
Ru basisAndExcluding cases. ) Amine compound represented by
Or its acid addition salt and containing it as an active ingredient
Antifungal agent. [0016] EXAMPLES In the compound (I) of the present inventionXAt
Chlorine, bromine, fluorine or iodine can be used as the rogen atom.
means. The addition of the amine compound represented by the general formula (I)
Examples of salting agents include hydrochloride, hydrobromide, and sulfuric acid.
Salt, nitrate, acetate, oxalate, tartrate, benzene
With drugs such as sulfonates and methanesulfonates
And acid addition salts that are acceptable. The compounds of the present invention are, for example, (A) General formula (II): [0019] [Chemical 19] (In the formula, R¹ And R ² Is the same as above, A is a leaving group
You. )And a compound represented by the general formula (III): [0020] [Chemical 20] (In the formula, R³ And R ^Five Is the same as above. )Represented by
Reacting with a compound, or (B) General formula (IV): [0021] [Chemical 21] (In the formula, R¹, R² And R ³ Is the same as above. )Represented by
Compound and general formula (V): [0022] [Chemical formula 22] (In the formula,R ^Five And AIs the same as above. )Represented by
React with compound, or (C) General formula (VI): [0023] [Chemical formula 23] (In the formula, R¹, R², R³ And R ^Five Is the same as above. )
Or a compound represented by (D) General formula (VII): [0024] [Chemical formula 24] (In the formula, R¹,R ³ And R ^Five Is the same as above. )Represented by
Obtained by reducing the compound
For recovering compounds as free bases or acid addition salts
Therefore, it can be manufactured. The above methods (a) and (b), or
Perform (c) and (d) in the usual manner.
It In the case of (a) and (b): For example, aromatic hydrocarbon
(Benzene or toluene), ethers (diethyl ether)
Ether or dioxane) or carboxylic acid
Reactions such as lucamide (dimethylformamide)
In a solvent, the reaction temperature between room temperature and the boiling point of the solvent (preferred
Or from room temperature to 60 ° C.). As leaving group A
Halogen atom (such as chlorine or bromine) or carbon number 1
An organic sulfonyloxy group having 10 to 10 (tosyloxy
Or mesyloxy etc.) and the like. Reaction is appropriate
Do acid binding agent ie alkali metal or alkaline earth
Metal hydroxides (sodium hydroxide or potassium hydroxide)
Or a carbonate (sodium carbonate or carbonate)
It is advantageous to carry out in the presence of (e.g. potassium). In the case of (c) and (d): For example, water as a reducing agent
Using lithium aluminum hydride, ethers (diethyl ether)
Ether, tetrahydrofuran or dioxane
Room temperature or the boiling point of the solvent and room temperature in an inert solvent such as
Can be carried out at the reaction temperature between. The compound of the present invention represented by the general formula (I)
From the free base to the acid addition salt and vice versa.
Each can be carried out in the usual way. The compound of the present invention represented by the general formula (I)
The starting materials (II), (II
Represented by I), (IV), (V), (VI) and (VII)
Most of the compounds are known compounds, but new compounds
Can be easily produced by a usual method. Made of them
An example is shown below. [0028] [Chemical 25] (In the formula, R¹, R², R³ andR ^Five IsSame as above. )
The reaction conditions may be those normally employed for such reactions,
Intermediates should be reacted further without isolation if appropriate
You can Even if you perform isolation
This can be done. The compounds of the present invention show excellent antifungal activity.
You Especially Trichophyton mentagrophyte
s), Trichophyton interdigitale, Trichophyton interdigitale
Trichophyton rubrum, Microsporum canis (Micro)
sporum canis), Microsporum gypseu
m), Epidermophyton floccosum, and crypt
Cryptococus neoformans
s), Sporothrix schen
ckii), Aspergillus fum
igatus), Candida albicans
In vitro test for fungi such as 0.025-100 μg
/ Ml antifungal activity. In addition, dermatomycosis model using guinea pig
In vivo test with a mouse (Sumio Sakai: Fungus and Mycosis Vol. 1 2
52 (Showa 35)), the compound of the present invention
It was found to have excellent activity against. The compounds of the present invention are solutions, ointments or cremes.
It may be provided as an antifungal agent in a dosage form such as a drug. Effectiveness
The concentration of the components depends on the fungus to be treated, the degree of disease,
It depends on the type of compound, dosage form, etc., but is generally 0.
It may be provided as an antifungal agent at a concentration of 01-5%. The following reference examples, examples, reference formulation examples, tests
The present invention will be described in more detail based on examples and reference test examples.
Obviously, the present invention is not limited to such an embodiment.
It is not something that can be done. The NMR spectra shown below are
Unless otherwise noted, TMS is used as a reference substance
Used, CDCl₃It is the δ value when measured inside. Also
The melting point of the example compound is the melting point of the hydrochloride salt,
Each shows the free base. Reference Example 1 Production of N-methyl-4-tert-butylbenzylamine 4-tert-butylbenzoic acid 178g and thionyl chloride 36
0 g was mixed and stirred at 50 ° C. for 5 hours. Then, under reduced pressure
After distilling off excess thionyl chloride, 40% methyl
The solution was added dropwise to 300 ml of an amine aqueous solution and stirred for 3 hours. With hydrochloric acid
N-methyl-4-tert-butylbenzoic acid by acidification
171 g of amide (melting point 99-100 ° C) was precipitated. 76.5 g of this amide compound was treated with lithium hydride.
Consisting of minium and 1 liter of anhydrous diethyl ether
The mixture was added and refluxed for 6 hours. When cold, excess hydrogenated lithium
The aluminum is decomposed by dropping it into water and
The tell layer was separated. After distilling off ether, vacuum distillation
Colorless liquid N-methyl-4-tert-butylbenzylamine
A point of 93 to 95 ° C / 6 mmHg) was obtained. NMR spectrum: 7.26 (s, 4H), 3.68 (s, 2)
H), 2.42 (S, 3H), 1.29 (S, 9H) Melting point of hydrochloride: 208.5 ~ 209.5 ℃ The following compound could be prepared in the same manner. N-ethyl-4-tert-butylbenzylamine (colorless liquid) Boiling point: 105-107 ℃ / 3mmHg NMR spectrum: 7.28 (s, 4H), 3.75 (s, 2H), 2.67 (g, J
= 7.5Hz, 2H), 1.33 (s, 9H), 1.12 (t, J = 7.5Hz, 3H) N-propyl-1-naphthylmethylamine (colorless liquid) Boiling point: 133-134 ℃ / 1.5mmHg NMR spectrum: 8.2-7.2 (m, 7H), 4.20 (s, 2H), 2.
69 (t, J = 7Hz, 2H), 1.86-1.15 (m, 2H), 0.9 (t, J = 7Hz, 3H) Reference example 2 N-methyl-N- (1-naphthylmethyl) 4-tert-butylpheny
Preparation of chloroacetamide 4-tert-butylphenylacetic acid
 Stir 1.92 g and thionyl chloride 3.6 g at 50 ° C for 3 hours.
It was After the reaction, the thionyl chloride was distilled off under reduced pressure to remove acid chloride.
I got a ride. N-methyl-1-naphthylmethylamine 1.71
g, 2 ml of triethylamine and 10 ml of anhydrous benzene
A solution of the above acid chloride dissolved in 10 ml of anhydrous benzene.
Was added dropwise and stirred for 4 hours. Pour the reaction into water and
Extracted with Zen, 3% hydrochloric acid, 3% aqueous sodium hydrogen carbonate solution
It was washed with water and washed with water, and dehydrated with sodium sulfate.
Benzene was distilled off to obtain a brown viscous amide compound. The following compounds can be similarly prepared.
did it. N- (4-tert-butylbenzyl) -N-methyl-1-
Naphthyl acetamide NMR spectrum (CDCl³Medium): 8 to 7 (m, 11H),
4.58, 4.47 (s, s, 2H), 4.14 (s, 2H), 2.97, 2.86 (s, s, 3
H), 1.27 (s, 9H) N- (4-tert-butylbenzyl) 1-naphthamide Melting point: 197-198 ° C N- (4-tert-butylbenzyl) -N-methyl-4-quinolincal
Bonamide NMR spectrum: 8.90 to 6.84 (m, 10H), 4.79, 4.17
(s, s, 2H), 3.09, 2.55 (s, s, 3H), 1.29, 1.23 (s, s, 9H) Reference example 3 N- (4-tert-butylbenzyl) -N-methyl-3-benzothio
Production of phenmethylamine N-methyl-4-tert-butylbenzylamine 0.89g, sodium carbonate
Mixture of 0.6 g thorium and 20 ml dimethylformamide
At room temperature, add 0.91 g of 3-chloromethylbenzothiophene
And allowed to stir. Pour the reaction mixture into water and extract with benzene.
Washed Add 1 ml of concentrated hydrochloric acid to the benzene solution, and under reduced pressure.
After distilling off benzene, recrystallize from ethanol to give colorless needles.
Crystals 1.4 g (melting point: 216-217.5 ° C.) were obtained. NMR spectrum: 8-7.2 (m, 9H), 3.74
(s, 2H), 3.54 (s, 2H), 2.21 (s, H), 1.30 (s, 9H) MS spectrum: 147 (reference peak), 148, 176, 23
2 (M⁺) Example 16 and Reference Examples 4 to 9 Hydrochloric acid of various amine compounds in the same manner as in Reference Example 3, respectively.
I got salt. The melting points of the compounds are shown in Table 1 together. [0041] [Table 1] Below, the NMR spectra and MS spectra of each compound
Raise (m / e). [0042]Reference example 4Compound obtained NMR spectrum: 8.2 to 7.1 (m, 12H), 3.90 (s, 2H),
3.73 (s, 2H), 2.20 (s, 3H) MS spectrum: 141, 147 (reference peak), 148, 1
70, 176, 317 (M⁺) Example1Compound obtained NMR spectrum: 8-7.2 (m, 12H), 3.73 (s, 2H), 3.
65 (s, 2H), 2.20 (s, 3H) MS spectrum: 141, 142, 1
47 (reference peak), 148, 170, 176, 317 (M⁺)Reference example 5 Compound obtained NMR spectrum: 8.15 to 6.83 (m, 13H), 3.91 (s, 2H),
3.81 (s, 2H), 2.19 (s, 3H) MS spectrum: 137, 149 (reference peak), 170, 1
88, 327 (M⁺) ExampleTwoCompound obtained NMR spectrum: 8.36 to 6.87 (m, 13H), 3.90 (s, 2)
H), 3.71 (s, 2H), 2.19 (s, 3H) MS spectrum: 137, 138, 149 (reference peak), 1
70, 188, 329 (M⁺)Reference example 6 Compound obtained NMR spectrum: 8.3 to 7.1 (m, 13H), 3.94 (s, 2H),
3.87 (s, 2H), 2.21 (s, 9H) MS spectrum: 137 (reference peak), 138, 170, 1
75, 204, 345 (M⁺) ExampleThreeCompound obtained NMR spectrum: 8.35 to 7.2 (m, 13H), 3.84 (s, 2)
H), 3.66 (s, 2H), 2.16 (s, 3H) MS spectrum: 137 (reference peak), 138, 170, 1
75, 204, 345 (M⁺)Reference example Compound obtained in 7 NMR spectrum: 8.32 to 7.11 (m, 13H), 3.92 (s, 2)
H), 3.83 (s, 2H), 2.19 (s, 3H) MS spectrum: 137 (reference peak), 138, 170, 2
19, 221, 248, 250, 389, 391 (M⁺) ExampleFourCompound obtained NMR spectrum (DMSO-d₆Medium): 8.47 ~ 7.45
(m, 13H), 3.92 (s, 2H), 3.72 (s, 2H), 2.16 (s, 3H) MS spectrum: 137 (reference peak), 138, 170, 2
19, 221, 248, 250, 389, 391 (M⁺)Reference example 8 Compound obtained NMR spectrum: 8.2 to 7.1 (m, 13H), 3.90 (s, 4H),
2.61 (s, 3H), 2.19 (s, 3H) MS spectrum: 137, 146 (reference peak), 147, 1
70, 184, 325 (M⁺) Example5Compound obtained NMR spectrum: 8.44 to 7.3 (m, 13H), 3.95 (s, 2)
H), 3.74 (s, 2H), 2.66 (s, 3H), 2.22 (s, 3H) MS spectrum: 137, 138, 146 (reference peak), 1
47, 170, 184, 325 (M⁺)Reference example 9 Compound obtained NMR spectrum: 8.57 to 7.23 (m, 13H), 3.85 (s, 2H),
3.66 (s, 2H), 2.16 (s, 3H) MS spectrum: 37 (reference peak), 138, 170, 18
6, 215, 356 (M⁺)Example6Compound obtained NMR spectrum: 8.55 to 7.3 (m, 14H), 4.40 (9, J =
6.5Hz, 1H), 3.70,3.63 (s, s, 2H), 2.21 (s, 3H), 1.59
(d, J = 6.5Hz, 3H) MS spectrum: 137 (reference peak), 146, 162, 17
0, 184, 198, 310, 325 (M⁺) Reference example10 N- (4-tert-butylbenzyl) -N-methyl-1-acenaphthene
Preparation of ruamine hydrochloride N-methyl-4-tert-butylbenzyl
1.71 g of amine, 2.12 g of sodium carbonate and dimethylphore
3.89 g of 1-bromoacenaphthene in a mixture of 10 ml of Lumamide
Was added and the mixture was stirred at room temperature for 19 hours. Pour the reaction solution into water,
It was extracted with benzene and washed with water. Remains after removing benzene
Dissolve the substance with a small amount of acetone, and add 2 ml of concentrated hydrochloric acid when cold.
It was Acetone and concentrated hydrochloric acid were removed under reduced pressure, and acetone was added.
-Recrystallized from a methanol mixture to give the title compound as white plate crystals.
I got 2.8g. Melting point: 233 to 234.5 ° C. NMR spectrum: 7.7 to 7.29 (m, 10H), 5.05 to 4.86
(m, 1H), 3.49 (s, 2H), 3.38-3.26 (m, 2H), 2.15 (s, 3H),
1.27 (s, 9H) MS spectrum: 144, 182 (reference peak), 314, 32
9 (M⁺) Reference example11 N- (4-tert-butyl-α-methylbenzyl) -N-methyl-1-
Manufacture of naphthylmethylamine N-methyl-1-naphthylmethylamine 1.71 g, sodium carbonate
4-tert in a mixed solution of 1.17 g of um and 10 ml of dimethylformamide.
-Butyl-α-methylbenzyl chloride 2.07 g was added.
And allowed to stir at 70-80 ° C for 24 hours. Pour the reaction solution into water,
It was extracted with benzene and washed with water. Concentrated hydrochloric acid in benzene solution 2
ml was added, benzene was distilled off under reduced pressure, and then acetone-meta
Recrystallized from nol solution to give 2.5g white crystals (melting point: 22
7.5 to 228.5 ℃). NMR spectrum: 8.23 to 7.32 (m, 11H),
3.92 (s, 2H), 3.76 (q, J = 6.5Hz, 1H), 2.11 (s, 3H), 1.47
(d, J = 6.5Hz, 3H), 1.30 (s, 9H) MS spectrum: 137 (reference peak), 150, 316, 33
1 (M⁺) Reference example12 N- (5-indanmethyl) -N-methyl-1-naphthylmethyla
Manufacture of min hydrochloride N-methyl-1-naphthylmethylamine 1.03g, Natri carbonate
In a mixed solution of 0.76 g of Um and 10 ml of dimethylformamide,
Add 0.76 g of 5-chloromethylindan and stir at 50 ° C for 17 hours.
Let it stir. Pour the reaction mixture into water, extract with benzene, and wash with water.
did. After removing the benzene, remove the residual oil with a small amount of acetonitrile.
The solution was dissolved in water and, when cold, 1 ml of concentrated hydrochloric acid was added. Aceto under reduced pressure
And concentrated hydrochloric acid were removed, and the mixture was mixed with acetone-ethanol.
The crystals were recrystallized to give 1.14 g of the title compound as white plate crystals. Melting point: 192-194 ° C NMR spectrum: 8.37 to 7.02 (m, 10H) Example7 and Reference Examples 13 to 17 Reference examples11and12Similar to various amines
The compound hydrochloride salt was obtained. The melting point of each compound is also shown in Table 2.
Shown in. [0046] [Table 2] Reference exampleCompound obtained in 13 NMR spectrum: 8.14 to 7.04 (m, 14H), 3.95 (s, 4H)
 , 2.54 (q, J = 7.5Hz, 2H), 1.07 (t, J = 7.5Hz, 3H) MS spectrum: 137 (reference peak), 138, 184, 3
10, 325 (M⁺) Example7Compound obtained NMR spectrum: 8.37 to 7.15 (m, 14H), 3.90 (s, 2H)
 , 3.60 (s, 2H), 2.49 (q, J = 7Hz, 2H), 1.00 (t, J = 7
Hz, 3H) MS spectrum: 137 (reference peak), 138, 184, 3
10, 325 (M⁺)Reference Example 14Compound obtained NMR spectrum: 8.12 to 7.06 (m, 14H), 3.97 (s, 4H)
 , 2.59 to 2.33 (m, 2H), 1.9 to 1.3 (m, 2H), 0.71
(t, J = 7Hz, 3H) MS spectrum: 137 (reference peak), 310, 339 (M
⁺)Reference example 15 Compound obtained NMR spectrum: 8.36 to 7.2 (m, 14), 3.98 (s, 2
H), 3.68 (s, 2H), 2.50 (t, J = 7Hz, 2H), 1.7 ~
1.1 (m, 2H), 0.75 (t, 3H) MS spectrum: 137 (reference peak), 138, 198, 3
10, 339 (M⁺)Reference Example 16 Compound obtained NMR spectrum: 8.11 to 7.0 (m, 14H), 3.93 (s, 4
H), 2.46 (t, J = 6.5Hz, 2H), 1.6 ~ 0.9 (m, 4H)
 , 0.69 (t, J = 6Hz, 3H) MS spectrum: 137 (reference peak), 138, 212, 3
10, 353 (M⁺)Reference Example 17 Compound obtained NMR spectrum: 8.4 to 7.35 (m, 14H), 4.06 (s, 2
H), 3.77 (s, 2H), 2.54 (t, J = 7HZ, 2H), 1.8 to 0.
9 (m, 4H), 0.77 (t, J = 6Hz, 3H) MS spectrum: 137 (reference peak), 138, 212, 31
0, 353 (M⁺) Reference formulation example 1 50g Macrogol 400 in 500ml ethanol and reference example
N- (4-tert-butylbenzyl) -N-methyl -3 prepared in 3
-Add 10 g of benzothiophene methylamine hydrochloride to dissolve
Dissolve, then add 400 g of purified water little by little to dissolve.
Ethanol was added to make the total volume 1000 ml. Reference formulation example 2 (ointment) White petrolatum 400g, cetanol 180g, sesquiole
50 g sorbitan acid salt, 5 g lauromacrogol and pa
A mixture of 1 g of propyl laoxybenzoate on a water bath
While maintaining the temperature at 80 ° C., the N- (4-tert-butane produced in Reference Example 3 was used.
(Cylbenzyl) -N-methyl-3-benzothiophenemethyla
10 g of min hydrochloride was added and dissolved. Further para-oxyne
Add 353g of purified water to 1g of methyl benzoate and heat to 80 ℃.
The resulting solution was gradually added and then thoroughly stirred. Heating
After stopping, the mixture was further stirred with cooling until it solidified. Reference formulation example 3 (cream) White petrolatum 15g, liquid paraffin 200g, stearyl
Alcohol 50g, Glycerin monostearate 40g,
145 g of ropylene glycol and p-hydroxybenzoic acid
While keeping a mixture of 1 g of ropil on a water bath at 80 ° C
Dissolved, N- (4-tert-butylbenzyl produced in Reference Example 3
) -N-Methyl-3-benzothiophene methylamine hydrochloride
10 g of salt was added and dissolved. 40 g of stearic acid
Refined to 40 g of Lioxy and 1 g of methyl paraoxybenzoate
498 g of water was added, and a solution that was heated to 80 ° C and dissolved was added.
After that, the mixture was sufficiently stirred. After stirring, cool with cooling water.
The mixture was further stirred until it solidified. Test Example 1 (In vitro antifungal test) Trichophyton mentagrophytes and Trichophyton rubrum using Sabouraud agar
The antibacterial activity against fungi was tested. Each test compound shown in Table 3 was treated with 1 ml of ethanol.
Dissolve in, and add distilled water to adjust the concentration to 1000 μg / ml.
Prepare a 2-fold serial dilution series, and shred 1 ml of it.
, Add 9 ml of Sabouraud agar medium and mix,
Each plate medium was prepared. 2 x 10⁶Mix each test bacterium adjusted to spores / ml
Clos Planter MIP-2 (made by Sakuma Seisakusho) without 0.005 ml
Growth after inoculation with 2 days of incubation at 27 ° C for 7 days
It was expressed as an inhibitory concentration (MIC, μg / ml). Obtained result
The fruitTable 3Shown in. As a result of the test, the test compounds shown in Table 3 were
All were found to have antifungal activity. [0053] [Table 3] Reference Test Example 1 (Antitinea treatment test) Back 4 of male Hartley guinea pig (weight 600-700g)
4 cm each²Remove each hair and lightly sandpaper
After culturing with guinea pig, it was previously back-cultured from another guinea pig 2
1x10 of 1st generation T. mentagrophytes per infected surface^FiveInfect spores
Let 48 hours after infection, test specimens were dissolved in ethanol
0.2 ml of the compound was applied once a day for a total of 10 times. Final treatment 2
Guinea pigs were slaughtered after 10 days, 10 from each infected surface
Tissue pieces of cycloheximide and kanamycin
Place it on a blow plate and incubate it at 27 ℃ for 7 days.
The presence or absence was judged and the inhibition rate was expressed as a percentage as follows. Inhibition rate = [1- (number of growing tissue pieces / reverse culture set)
Number of woven pieces)] × 100 The obtained results are shown in Table 4. [0055] [Table 4] Reference test example 2 (side effect test) In order to investigate the side effects of test compounds, Hartley guinea pigs
4c for each of the two backs of a male (weight 600-700g)
m²Remove the hair one by one and rub the area to be removed with sandpaper the next day.
After that, each of the compounds of Reference Example 3 was tested as a test compound.
Remove the solution dissolved in ethanol with a concentration of 0.5 to 2.0%
For one of the parts, only ethanol is applied to the other hair removal parts
0.2 ml was applied once a day for 10 days each. As a result, it is considered that it depends on the test compound.
No side effects such as erythema and papules were observed. [0057] The amine compound of the present invention is an excellent antifungal.
It has activity and is useful as an antifungal agent.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Toshiyuki Yamamoto             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center (72) Inventor Kazuya Sasaki             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center (72) Inventor Yes Yes             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center (72) Inventor Mamoru Yokoo             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center (72) Inventor Rieko Hashimoto             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center (72) Inventor Koji Amemiya             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center (72) Inventor Sakae Koshikawa             2-28-8 Honkomagome, Bunkyo-ku, Tokyo             Pharmaceutical Co., Ltd. Tokyo Research Center              (56) References JP-A-61-282348 (JP, A)               JP-A-53-46924 (JP, A)               JP-A-52-46301 (JP, A)               JOURNAL OF THE CHE             MICAL SOCIETY. C. ORG             ANIC CHEMISTRY, No. 13             (1971) P. 2428-2430

Claims (1)

Claims 1 General formula (I): (In the formula, R ¹ is the formula: (In the formula, X represents a hydrogen atom, a halogen atom or a methyl group.
R ² represents a hydrogen atom or a methyl group,
R ³ represents a methyl group or an ethyl group, and R ⁵ has the formula: Indicates. However, R ¹ is represented by the formula: In a group represented, R ² is hydrogen atom, R ³ excluding a methyl group der Rubaai. ) The amine compound or its acid addition salt represented by these. 2 General formula (I): (In the formula, R ¹ is the formula: (In the formula, X represents a hydrogen atom, a halogen atom or a methyl group.
R ² represents a hydrogen atom or a methyl group,
R ³ represents a methyl group or an ethyl group, and R ⁵ has the formula: Indicates. However, R ¹ is of the formula: In a group represented, R ² is hydrogen atom, R ³ excluding a methyl group der Rubaai. ) An antifungal agent containing an amine compound represented by the formula (4) or an acid addition salt thereof as an active ingredient.