JPH0720977B2 - Cilatran compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention provides a silatrane compound represented by a specific structural formula, a bactericidal agent and an anticancer agent containing the silatrane compound as an active ingredient.

(Prior Art) With regard to organosilicon compounds, research has been conducted on synthesis and physiological activity, and it is known that a specific group of organosilicon compounds has excellent physiological activity such as antitumor activity and antibacterial activity. .

Among the organosilicon compounds, a compound called silatrane represented by the following formula was found to have various physiological activities such as antibacterial / antifungal action, insecticidal action, rodenticidal action, hair growth promoting action, and antitumor intestinal action. Has been.

(However, R represents a substituted or unsubstituted alkyl group, an alkoxy group, or a phenyl group.) Further, as a silatran compound having an imino bond (C = N bond) in the molecule, a compound represented by the following formula 5 Only one species was synthesized by Lukevic et al. And only reported to show some anti-tumor effect on Ehrlich cancer in mice [Izv, Akad. .Nauk.
Latv.SSR), 338 (1978)].

(Wherein, X is _{Cl, OH, OCH 3, NO} 2, showing the _{N (C 2 H 5) 2} .) ( To be Solved by the Invention Problems) However, the poor effect as a carcinostatic of these compounds Therefore, it is desired to search for new compounds having not only a superior anticancer effect but also a wide range of physiological activities.

(Means and Effects for Solving Problems) For many years, the present inventor has synthesized many novel organosilicon compounds and has continued research on various physiologically active actions of the organosilicon compounds.

As a result, the present inventor succeeded in synthesizing a group of silatran compounds represented by the following general formula, and found that the compound group expresses unrivaled remarkable anticancer activity and bactericidal activity. Has been completed and has come to be proposed here.

That is, the present invention provides the following general formula (1) (In the formula, R represents a hydrogen atom or an alkyl group, X represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group, a benzoyloxy group, Y and Z represent a different or the same kind of halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group and a benzoyloxy group, and Y and Z are adjacent to each other to form a ring. Which may be formed, n represents an integer of 1 or more, and m represents 0 or 1.), and a fungicide and a carcinostatic agent containing the compound as an active ingredient.

In the general formula (1), the number of carbon atoms of the alkyl group represented by R is not particularly limited, and a linear or branched group is used, but the number of carbon atoms is 1 to 6 because of easy availability of raw materials. Is preferred. Specific examples of the alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group and a hexyl group. Also, in the general formula (1), X, Y
Specific examples of the halogen atom represented by and Z include chlorine, bromine, fluorine and iodine atoms. or,
As the alkyl group, the groups described for R above are preferably used. Further, it is preferable that the alkyl group contained in the alkoxy group, the alkylthio group and the alkoxycarbonyl group also has 1 to 6 carbon atoms, like the alkyl group described above. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentoxy group, and a hexoxy group, and specific examples of the alkylthio group include a methylthio group, an ethylthio group, a propylthio group, a butylthio group, a pentylthio group, and a hexylthio group. A group such as a methoxycarbonyl group as a specific example of an alkoxycarbonyl group,
Examples thereof include an ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group and a pentoxycarbonyl group.

Further, in the general formula (1), the ring formed by Y and Z adjacent to each other is Is preferred. Also above One or more hydrogen atoms in the ring represented by may be substituted with other substituents. As such a substituent, a halogen atom, a hydroxy group, an alkyl group, an alkoxy group, an alkylthio group, a cyano group and the like are preferable.

In the general formula (1), n may be an integer of 1 or more, but n is an integer of 1 to 4, particularly n is an integer from the viewpoint of easy availability of raw materials.
It is preferably 1,3 or 4.

The silatrane compound of the present invention is a crystalline solid having a constant melting point in most cases at room temperature and atmospheric pressure, and is rarely a viscous substance.

The fact that the silatrane compound has the chemical structure represented by the general formula (1) can be generally confirmed and fixed by the following means (a) to (e).

(A) By measuring the infrared absorption spectrum (IR), it is possible to confirm the types of characteristic chemical bonds and functional groups present in the silatrane compound molecule. For example the silatrane compound absorption based on the CH bond in the vicinity of 3000~2800cm ^-1, indicating the absorption based on CR = N bond to 1650~1600cm ^-1. Further, when m = 1 in the silatrane compound represented by the general formula (1), absorption due to an NH bond is exhibited at 3500 to 3300 cm ⁻¹ .

(B) Measure each mass spectrum (MS) and observe each
(Generally, the molecular weight m of the ion is divided by the charge number e, m /
to calculate the composition formula corresponding to the number represented by e)
Therefore, the binding mode of the sample used for measurement and ultimately
The molecular weight of can be estimated. That is, it was subjected to measurement
Samples with general formula(However, R, X, Y, Z, n and m are those shown in the general formula (1).
Is the same as ), It is generally equivalent to the molecular weight.
Molecular ion peak (M ), From the molecular ion peakCorresponding to the peak, and at m / e174A strong peak corresponding to appears.

(C) ¹³ by measuring the C- nuclear magnetic resonance spectrum ⁽¹³ C-NMR), the number of carbon atoms of the silatrane compound was subjected to the measurement, the mode of arrangement of the carbon chain, to know the binding mode of carbon atoms I can. That is, in ¹³ C-NMR (tetramethylsilane standard), a unique peak based on each ^{13 C} is observed depending on the types of R, X, Y, Z, n and m in the above general formula (1). To be done.

For example, in the general formula (1), when R is a hydrogen atom, n is 3, m is 0, and X, Y, and Z are methoxy groups at the 3-, 4-, and 5-positions, respectively, the silatran compound is a deuterated chloroform solvent. The results of ¹³ C-NMR measurement and analysis thereof were as follows (chemical shift values: δ, ppm).

(D) by measuring the ¹ H- nuclear magnetic resonance spectra ⁽¹ H-NMR), the number of hydrogen atoms of the silatrane compound was subjected to the measurement, it is possible to know the bonding mode of hydrogen atoms. That is, in ¹ H-NMR (based on tetramethylsilane), depending on the types of R, X, Y, Z, n and m in the above general formula (1), a unique peak based on each ¹ H To be observed.

For example, deuterated chloroform for a silatran compound in which R in the general formula (1) is a hydrogen atom, n is 3, m is 0, X is a hydrogen atom, Y is a chlorine atom at the 2-position, and Z is a fluorine atom at the 6-position. In ¹ H
-The results of NMR measurement and analysis were as follows (chemical shift values: δ, ppm).

(E) Obtain each weight% of carbon, hydrogen, nitrogen, silicon (halogen and sulfur when halogen and sulfur are included) by elemental analysis, and then subtract the sum of the weight% of each recognized element from 100. By weight of oxygen
Can be calculated and thus the composition formula of the silatrane compound can be determined.

The properties of the silatrane compound of the present invention are slightly different depending on the values of n and m and the types of R and Ar in the general formula (1), but generally they are white, light yellow and light brown at room temperature and normal pressure. It is a yellow, orange yellow, orange, red, deep red crystalline solid, but it may be a viscous substance. The silatrane compound is relatively well soluble in a chlorine-based solvent such as chloroform and methylene chloride, an alcohol-based solvent such as methanol and ethanol, a polar nonaqueous solvent such as N, N-dimethylformamide and dimethyl sulfoxide, and benzene, toluene, It is soluble in ether, tetrahydrofuran, dioxane, etc., sparingly soluble in hexane and ligroin, and insoluble in water.

The method for producing the silatrane compound of the present invention is not particularly limited, and any method may be used. A typical manufacturing method that is generally suitably adopted will be described below. That is, the general formula (2) [In the formula, R, X, Y, Z, n and m are the same as those shown in the general formula (1), and R'is an alkyl group. ] The target silatrane compound of the present invention can be obtained in good yield by reacting a trialkoxysilane represented by the following with triethanolamine. The above reaction formula is shown below. The trialkoxysilane represented by the above formula is not limited to its production method, and those obtained by known production methods can be used without particular limitation. Specific examples of the alkyl group represented by R'in the general formula include methyl group, ethyl group, n-propyl group, is
Examples thereof include o-propyl group and n-butyl group. A catalyst is preferably used in the above reaction. The catalyst can be used without particular limitation as long as it cuts the silicon-bonded alkoxy group to carry out the exchange reaction with triethanolamine, but potassium hydroxide, lithium hydroxide, sodium hydroxide can be used. Basic compounds represented by alkali metal hydroxides such as ## STR3 ## are preferable because they are often effective even in a small amount. A typical example of the above reaction will be described in detail in Examples described later. The reaction can be carried out without a solvent, but it is generally carried out in the presence of a solvent. The solvent can be used without particular limitation as long as it is a solvent that does not react with raw materials, products or catalysts, and generally, alcohol solvents such as ethanol, methanol and isopropyl alcohol, dimethoxyethane, dioxane and acetonitrile are used. It is preferably used. The reaction conditions are not particularly limited, but generally 0 to 200 ° C, preferably 20 to 150 ° C.
It is sufficient to select the temperature within the range of several minutes to several days, and usually within the range of 5 minutes to 50 hours. The reaction pressure is usually atmospheric pressure because the reaction proceeds sufficiently under atmospheric pressure, and may be carried out under pressure or under reduced pressure as necessary.

The silaton compound of the present invention has the general formula (3) (However, n and m are the same as those in the general formula (1).) And an aminoalkyl silatrane represented by the general formula (4). (However, R and X, Y, and Z are the same as those in the general formula (1).) Alternatively, a carbonyl compound represented by the formula: The reaction formula is shown below.

A typical example of the above reaction will be described in detail in Examples described later, but the reaction is generally performed in the presence of a solvent. The solvent can be used without particular limitation as long as it is a solvent that does not react with raw materials or products, and is generally benzene, toluene, ethanol, propanol, acetonitrile, N, N-dimethylformamide, chloroform, tetrahydrofuran, dioxane, Dimethoxyethane and the like are preferably used. The reaction conditions are not particularly limited, but generally 0 to 200 ° C, preferably 20 to 150 ° C.
It is sufficient to select at a temperature of ℃ for several minutes to several days, usually 10 minutes to 50 hours. Further, the reaction is a so-called dehydration reaction, and water is produced with the progress of the reaction. Therefore, benzene, chloroform, ethanol, toluene or the like having a property of azeotroping with water as a solvent is used, and the reaction solution is heated under reflux,
It is convenient to use a means for azeotropically removing the produced water to the outside of the system, or to use a dehydrating agent or a dehydrating catalyst, if necessary, in order to allow the reaction to proceed efficiently.

The silatran compound of the present invention is usually obtained in good yield by using each raw material at an equimolar ratio according to any of the above reaction formulas. When the silatran compound precipitates as crystals after completion of the reaction, it can be obtained as an extremely pure product by filtering the crystals. When the silatrane compound is dissolved in the solution even after the reaction is completed, it can be obtained by removing volatile components such as a solvent by means of atmospheric distillation, reduced pressure distillation, vacuum distillation or the like. The silatran compound thus obtained is generally a pure product, but if it is necessary to obtain a highly pure silatran compound, a purification means such as recrystallization or reprecipitation can be used.

The silatrane compound of the present invention has remarkably excellent physiological activity and exerts an excellent anticancer activity. For example, it exerts an extremely strong antitumor effect against Ehrlich ascites tumor in mice and Walker Carcinosarcoma 256 ascites tumor in rats. From these effects, the silatrane compound of the present invention can be suitably used for the purpose of preventing, treating or treating various cancers. As is clear from Examples described later, the antitumor activity of the silatrane compound varies depending on the values of n and m in the general formula (1) and the types of R, X, Y and Z. 3, R is a hydrogen atom or a methyl group, Y is a hydroxy group and Z is a hydroxy group, or an alkyl group, Y is a halogen atom and Z is a halogen atom, or a nitro group Where Y and Z are both nitro groups, Y and Z are adjacent to each other A group represented by and a group in which X, Y and Z are all alkoxy groups tend to show particularly strong activity. Specific examples of the substituent include dihydroxyphenyl group, dialkyl-hydroxyphenyl group, chloro-fluorophenyl group, chloro-nitrophenyl group, chloro-hydroxy-group.
Alkylphenyl group, dinitrophenyl group, trialkoxyphenyl group, hydroxy-naphthyl group, halogenonaphthyl group, cyanonaphthyl group, alkylthio-naphthyl group, etc. are listed, and the number of substituents of phenyl group contained in silatrane compound is one. It can be confirmed that the case where the silatrane compound of the present invention has two or more substituents, as compared with the case where there is a certain case, tends to exhibit stronger antitumor activity.

When the silatrane compound of the present invention is used as an anticancer agent, any known form can be used. As a typical example of the use form, oral,
It can be administered to a patient either parenterally (eg intramuscularly, intravenously, subcutaneously, intraperitoneally, intrarectally) or locally. The effective dose of the silatrane compound, which is the active ingredient in that case, varies depending on the age of the patient to be administered, the body weight, the severity of the symptoms, the type of cancer, etc., but generally 200-0.0.
It may be 02 mg / kg / day, preferably 50 to 0.02 mg / kg / day. The daily dose can be administered only once a day or divided into several times a day (3 to 5 times). Further, it goes without saying that the above-mentioned dose is merely a guideline, and it is possible to administer over the above-mentioned range depending on the judgment of the treating doctor.

Upon administration of the above-mentioned active ingredient, the above-mentioned silatrane compound can be formulated into various dosage forms depending on the desired administration method (oral, parenteral or topical).

For example, for oral administration, it can be formulated into a dosage form such as tablets, pills, dragee tablets, powder sachets, granules, syrups, capsules, etc., and for parenteral administration, a solution or suspension, a suppository. And the like.

The concentration of the active ingredient in these preparations is not particularly limited and can be widely varied depending on the dosage form, but is generally 0.05 to 90% by weight, preferably 1 to 60% by weight.
The concentration can be moderate.

As the excipient that can be used in the above-mentioned formulation, any of those commonly used in the art can be used, and for solid-state formulations, for example, lactose, sucrose, starch, glycine, crystalline cellulose, mannose. Knit, magnesium stearate, liquid paraffin, calcium carbonate, sodium hydrogencarbonate and the like. For liquid form preparations, for example, physiological saline, surfactant solution, glucose solution, alcohol, esters, etc. Can be mentioned.

The specific examples of such preparations are as follows.

Formulation Example 1: Injectable Aseptically dispensed into vials to contain the predetermined amount of silatrane compound and sealed to remove water and bacteria. Before use, a prescribed amount of physiological saline containing lidocaine 0.5% may be added to obtain an injection.

Formulation Example 2: Capsules Lactose (4.5 parts by weight) is added to magnesium stearate (0.6 parts by weight), and the mixture is stirred and mixed until homogenized.
1 part by weight and 10 parts by weight of crystalline cellulose are added and mixed. To this mixture, 20 parts by weight of the above-mentioned finely pulverized silatrane compound was added and mixed again to obtain a prepared powder.
Capsules may be manufactured by filling gelatin capsules with this powder using a capsule filling machine.

Formulation Example 3: Tablets 25 parts by weight of silatrane compound and 20 parts by weight of mannitol were thoroughly mixed and pulverized, and then potato starch 4.7 as starch paste was prepared.
Add parts by weight to granulate. The particles are passed through a 60 mesh screen, dried to a specified weight and screened through a 16 mesh screen. Next, the particles were treated with magnesium stearate
It may be mixed with 3 parts by weight, smoothed, and compressed by a tablet molding machine by a conventional method to give tablets of an appropriate size.

Furthermore, the silatrane compound of the present invention exerts a very broad and excellent effect not only on the anti-cancer activity but also on the bactericidal activity, as will be apparent from the examples described later. The bactericidal activity is found in almost all of the silatrane compounds represented by the above general formula (1), but by selecting the values of n and m in the general formula and the types of R and X, Y, Z It shows excellent activity. Generally, n is 3, R
Those having a hydrogen atom or a methyl group tend to exhibit strong activity. Y is a hydroxy group and Z is a hydroxy group, an alkyl group, or an alkoxy group, Y
Is a halogen atom and Z is a halogen atom or a nitro group, Y and Z are both an alkoxy group or a nitro group, and Y and Z are adjacent to each other. The group represented by and the group in which X, Y and Z are all alkoxy groups tend to show particularly excellent activity. Specific examples of the substituent include dihydroxyphenyl group, alkoxy group-hydroxyphenyl group, dialkyl-hydroxyphenyl group, chloro-fluorophenyl group and chloro-
Examples thereof include a nitrophenyl group, a dialkoxyphenyl group, a dinitrophenyl group and a trialkoxyphenyl group.

The silatrane compound of the present invention can be widely applied to a wide variety of pathogens belonging to, for example, basidiomycetes, soybean fungi, ascomycetes, incomplete fungi, and bacteria, and therefore, the activity of agricultural chemicals or pharmaceuticals. It can be said that it is extremely useful as a component.

Specific examples of the fungi in which the silatrane compound of the present invention exhibits extremely strong bactericidal activity include, for example, wilt fungus, sesame leaf blast fungus, vine blast fungus, Botrytis cinerea, white bacterium, Staphylococcus aureus and the like.

The silatrane compound of the present invention, production examples thereof, and bioactivity test examples are shown below. However, the present invention is not limited to these.

Example 1 N- (3,4,5-trimethoxyphenylmethylidene) -γ-a
Minopropyltriethoxysilane (9.46g), Trieta
Nolamine (3.53g), potassium hydroxide (0.18g),
The mixture of tanol (20 ml) was heated under reflux for 2 hours and then cooled.
Light pink color with a melting point of 128-129 ℃ when left in place.
Crystals (5.96 g) were obtained. Infrared absorption spectrum of the product
When the tor was measured, the spectrum as shown in Fig. 1 was obtained.
Is obtained, 1635 cm^-1Shows absorption based on CH = N bond
It was Its elemental analysis values are C54.97%, H7.39%, N7.17%.
, C₁₉H₃₀N₂O₆Calculated value for the composition formula Si (410.54)
C55.58%, H7.37%, N6.83%. Also the mass
The spectrum was measured and found to correspond to the molecular weight of m / e410.
Molecular ion peak (M ), M to e / m ‐C₆H₂(OC
H₃)₃The peak corresponding to, N (CH₂CH₂O)₃Si Corresponding to
Showed a peak. further¹³As a result of measuring C-nmr,
The spectrum as shown in Figure 2 was obtained and the observed
Kurk was attributed as follows.

From the above results, it was revealed that the obtained product was N- (3,4,5-trimethoxyphenylmethylidene) -γ-aminopropylsilatrane. The yield was 61.3%. The compound number of the compound is No.1.

Example 2 N- (1-hydroxynaphthyl-2-methylidene) -γ-ami
Nopropyltriethoxysilane (10.15g) and triethano
With amine (4.03 g) in the same manner as in Example 1,
Yellowish brown crystals with a melting point of 67-70 ℃ by post-treatment
(9.26g) was obtained. Infrared absorption spectrum of the product
When the spectrum is measured, the spectrum shown in Fig. 3
Obtained, 3280 cm^-1Absorption based on a wide range of OH bonds, 1630 cm
^-1Shows absorption based on CH = N bond. Mass spectrum
Was measured to find that the molecular ion corresponding to the molecular weight was m / e386.
Peak (m ), M (e174) N (CH₂CH₂O)₃Si Corresponds to
Showed a peak. further¹³The result of measuring C-nmr is
As shown in FIG. 4, it was assigned as follows.

From the above results, it was revealed that the obtained product was N- (2-hydroxynaphthyl-1-methylidene) -γ-aminopropylsilatrane. The yield was 88.7%. The compound number of the compound is No.2.

Example 3 γ-aminopropyl silatrane (4.09 g), 2-chloro-6
-Fluorobenzaldehyde (2.79g), benzene (30m
The mixture of l) is heated under reflux for 1 hour, and the produced water is azeotropically distilled.
The reaction was carried out while removing it. In the reaction solution
Add hexane (30 ml) and let it stand in the cool place by heating.
This gave pale yellow crystals (2.61g) with a melting point of 107-110 ℃.
It was The infrared absorption spectrum of the product was measured.
Around 1640cm, the spectrum shown in Fig. 5 was obtained.
^-1Shows absorption based on CH = N bond. Elemental analysis value
Is C50.36%, H6.09%, N7.76%, and C₁₆H_{twenty two}N₂O₃ClFS
Calculated value for composition formula i (372.91) C51.53%, H5.95
%, N 7.51%. Also, measure the mass spectrum
A peak of the molecular ion corresponding to the molecular weight at m / e 373
(M ), M / e243 from the molecular ion peak to 2-chloro-6-
A peak that is considered to have eliminated the fluorophenyl group [M
‐C₆H₃ClF], m / e 174 N (CH₂CH₂O)₃Si Corresponding to
Indicated. Furthermore, regarding the compound, tetramethyl
Run in deuterated chloroform¹H-nuclear magnetic resonance scan
Vector (¹H-NMR) was measured and it is shown in FIG.
Unusual spectrum was obtained and the result of analyzing the spectrum
Was as follows (chemical shift value: δ, ppm).

From the above results, the obtained pale yellow crystals were N- (2-chloro-
It was revealed to be 6-fluorophenylmethylidene) -γ-aminopropylsilatrane. Yield 39.8%
Met. The compound number of this compound is No. 3.

Example 4 The following one was prepared by the same method as described in Examples 1-3.
A silatrane compound represented by the general formula was synthesized. Silatra
Compounds, structures, physical properties, instrumental analysis results, and yields
Are also shown in Table 1. The compounds shown in Table 1
The mass spectrum of
And the molecular ion peak (M ) And m / e1
74 has a silatranyl group, i.e.A peak corresponding to was observed.

Example 5 The compound of No. 2 obtained in Example 2 was added to physiological saline containing the surfactant Tween 80 to prepare a suspension containing a specified amount of sample, and this sample solution was used to prepare a suspension. The anti-tumor activity of Ehrlich ascites tumor in mice was tested.

That is, the sample solution was intraperitoneally administered to each of 6 Swiss mice (female) having 5 × 10 ⁶ Ehrlich's cancer cells by intraperitoneal injection of 0.5 ml for 9 consecutive days. The mean survival time (MST) was calculated from the results of the life-prolonging effect over 55 days, and the control group (30
T / C (%) was calculated by comparison with the average number of days of survival of each animal. That is, the average number of days to survive was calculated for the test body (T) and the control body (C), and calculated as T / C × 100 (%). The approximate value is determined by taking the number of days when the 4th animal out of 6 test subjects died as the average number of days to survive, and dividing this by the average number of days to survive similarly determined from the control body, and then multiplying by 100. Second result
Shown in the table. However, although 30 mice were used as a control group, the average value of 6 mice is shown in the table.

From the above results, it was clarified that the compound No. 2 exhibits remarkable antitumor activity against Ehrlich's cancer.

Comparative Example The silatran compound represented by the following general formula was tested for antitumor activity against mouse Erich Ascites tumor in the same manner as in Example 5.

The results are shown in Table A.

Example 6 The compound No. 5 obtained in Example 4 was tested for activity against mouse Ehrlich ascites tumor in the same manner as in Example 5. As a result, at the doses of 100 mg / kg and 50 mg / kg, the number of surviving animals out of 6 was 4, MST was 55.0 days or more, T / C (%) was 337 or more, and No. 5 compound was extremely high. It was confirmed to have high antitumor activity.

A sample solution was prepared by suspending a prescribed amount of the compound of Example 7 No. 5 in a physiological saline solution containing the surfactant Tween 80.

This sample solution was intraperitoneally injected into 6 Sprague Dawley rats (female) having 1 × 10 ⁵ Walker Carcinosarcoma 256 cancer cells in the abdominal cavity for 5 consecutive days for 30 days. The life extension effect was investigated over. The results are shown in Table 3.

From the above results, it was confirmed that the compound of No. 5 had extremely high antitumor activity against the 256 tumors of weeker carcinosarcoma.

Example 8 For the compounds obtained in Examples 1, 3 and 4, Example 5
Similarly to the above, the activity test against Ehrlich's ascites tumor of mice was performed. The results are shown in Table 4.

Example 9 A nutrient medium containing 1.5% agar was sterilized by heating at 121 ° C. for 15 minutes, then cooled to 50 ° C., and a suspension of pre-grown cells or spores in sterile water was added. It was mixed well, poured into a petri dish, and solidified into a flat plate. Example 2
A circular filter paper having a diameter of 8 mm was dipped in a methanol solution containing about 15% of the No. 2 compound synthesized in 1. to remove the excess on the filter paper, and the plate was placed on a solidified agar medium. 24-48 at about 30 ° C
After culturing for a period of time, the diameter of the inhibition circle was measured. Cocliobolus miyabenas (CM), pellicularia sasaki (PS), fusarium oxysporum (FO), trichophyton mentaglophytes (TM), trichophyton rubrum (TR), microsporum gypseum (M)
G), Botrytis cinerea (BC), Staphylococcus aureus (SO), Aspergillus niger (A)
N), Candida albicans (CA). The results of the antibacterial test are shown in Table 5. All the test bacteria in Table 5 are indicated by abbreviations.

From the above results, it was revealed that the compound No. 2 exhibits excellent antibacterial activity.

Example 10 The compounds synthesized in Examples 1, 3 and 4 were subjected to an antibacterial test in the same manner as in Example 9, the diameter of the inhibition circle was measured, and the results are shown in Table 6. In Table 6, all the test bacteria are also described by abbreviations, and the numerical values following the abbreviations represent the diameter of the inhibition circle for the test bacteria indicated by the abbreviations in mm.

[Brief description of drawings]

FIG. 1, FIG. 3 and FIG. 5 show infrared absorption spectra of the silatrane compounds of the present invention obtained in Example 1, Example 2 and Example 3, respectively. Further, FIG. 2 and FIG. 4 show ¹³ C-nuclear magnetic resonance spectra of the silatran compounds obtained in Example 1 and Example 2, respectively. Furthermore, FIG. 6 shows the ¹ H-nuclear magnetic resonance spectrum of the silatrane compound obtained in Example 3.

Claims (3)

[Claims] 1. A general formula (In the formula, R represents a hydrogen atom or an alkyl group, X represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group, a benzoyloxy group, Y and Z represent a different or the same kind of halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group and a benzoyloxy group, and Y and Z are adjacent to each other to form a ring. Which may be formed, n represents an integer of 1 or more, and m represents 0 or 1.). 2. General formula (In the formula, R represents a hydrogen atom or an alkyl group, X represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group, a benzoyloxy group, Y and Z represent a different or the same kind of halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group and a benzoyloxy group, and Y and Z are adjacent to each other to form a ring. Which may be formed, n represents an integer of 1 or more, and m represents 0 or 1.) A fungicide containing the silatran compound represented by the formula (1) as an active ingredient. 3. General formula (In the formula, R represents a hydrogen atom or an alkyl group, X represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group, a benzoyloxy group, Y and Z represent a different or the same kind of halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a hydroxy group, a nitro group, a cyano group, an alkoxycarbonyl group and a benzoyloxy group, and Y and Z are adjacent to each other to form a ring. Which may be formed, n is an integer of 1 or more, and m is 0 or 1.) An anticancer agent comprising a silatrane compound represented by