JPS637552B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is a novel compound substituted phenylureidopropyltrialkoxysilane, namely:
general formula [However, R is an alkyl group, and X is a sulfamoyl group or a bis(β-chloroethyl)amino group]. Traditionally, functional alkylsilane compounds, such as γ
It is known that functional propylsilane compounds such as -aminopropyltriethoxysilane and γ-(glycidyloxy)propyltriethoxysilane are used as water repellent treatment agents for fiber surfaces, rust preventive agents, and the like. Furthermore, the general formula obtained by reacting γ-aminopropyltriethoxysilane and an organic isocyanate γ-(organoureido)propyltriethoxysilane (where Ar represents an organic group) is also a known compound as shown in US Pat. No. 2,907,782. However, none of these known documents describes the physiological activity of organosilicon compounds. The present inventors have continued research on the synthesis of various useful functional organosilicon compounds for many years. As a result, the general formula,
(RO) ₃ SiCH ₂ CH ₂ CH ₂ NCO (however, R is an alkyl group) γ-isocyanatopropyltrialkoxysilane and the general formula,

[46.0]

(CH ₃ CH ₂ ) ₃ N [8.6] From the above results, the white solid obtained is γ-[p
-(Bis-β-chloroethyl)aminophenylureido] It was found to be a 1:1 molar mixture of propyltriethoxysilane and triethylamine hydrochloride. Transfer the white solid (7.12 g) to a mortar and add water (50 g) to a mortar.
ml) was added, crushed well and stirred, followed by suction filtration. The same operation was repeated three more times for the solids collected by filtration. White needle-like crystals were obtained by distilling off water from the filtrate under reduced pressure. When elemental analysis was performed, the measured values were C51.35%, H11.71%, N10.08%, and the calculated values were C52.35%, H11.72% for the composition formula C ₆ H ₁₆ NCl (137.66). , N10.18%. Furthermore, we measured the infrared absorption spectrum,
Comparison with the standard product revealed that the crystals obtained from the filtrate were triethylamine hydrochloride. Furthermore, when ^{the 13} C-nuclear magnetic resonance spectrum of the filtered solid was measured in deuterated chloroform, the results were in good agreement with the measurement results described above, except that the peaks at 46.0 ppm and 8.6 ppm disappeared. Furthermore, several characteristic peaks in the 2800 to 2300 cm ^-1 region due to triethylamine hydrochloride disappeared in the infrared absorption spectrum. From the above results, it is clear that the solid obtained by washing with water does not contain triethylamine hydrochloride.
It was revealed that it was (bis-β-chloroethyl)aminophenylureido]propyltriethoxysilane. Example 3 γ-Aminopropyltriethoxysilane (3.45
g, 0.016 mole) in ether solution (30 ml) of p-
Sulfamoyl phenyl isocyanate (3.09
An ether solution of 0.016 g, 0.016 mole) was added dropwise to the mixture under ice-water cooling, and the mixture was stirred overnight at room temperature. The reaction mixture was further heated under reflux for 5 hours. The solvent was removed by distillation to give a white solid (6.54g). By measuring the infrared absorption spectrum and mass spectrum of the solid, it was determined that the solid was the same as the product obtained in Example 1, that is, γ-(P-sulfamoylphenylureido)propyltriethoxysilane. It became clear that. Example 4 Various substituted phenylureidopropyltrialkoxysilanes were synthesized by methods similar to those described in Examples 1-3. The obtained substituted phenylureidopropyltrialkoxysilane is summarized in Table 1 along with the elemental analysis results, reaction raw material composition, and reaction conditions. In addition, when the substituents (X) on the phenyl side are the same, the infrared absorption spectrum of the propyltrialkoxysilane has a slight difference in the absorption region (3000 to 2800 cm ^-1 ) based on the alkoxy group and the constituent alkyl bond. They were almost the same except for some differences. Furthermore, in the mass spectrum of the propyltrialkoxysilane, a weak molecular ion peak (M) and a relatively strong peak [(RO) ₃ Si] based on the trialkoxysilyl bond were observed. However, the molecular ion peak tends to become weaker as the molecular weight increases, and was hardly observed when the molecular weight was 500 or more.

【table】

[Table] Reference Example 1 Methanol (50 ml) and water (30 ml) were added to γ-(p-sulfamoylphenylureido)propyltriethoxysilane (9.07 g, 0.022 mole) obtained in Example 1, and the mixture was heated to room temperature. After stirring overnight, the mixture was heated to 60°C on a water bath for 1 hour. Low-boiling substances were distilled off from the reaction mixture under reduced pressure, and then vacuum-dried at 70°C for 5 hours to obtain γ-(p-sulfamoylphenylureido)propyl polysilsesquioxane (6.32 g) as a white solid. Obtained. Reference Example 2 A 1:1 mixture (4.00 g) of γ-[p-(bis-β-chloroethyl)aminophenylureido]propyltriethoxysilane and trimethylamine hydrochloride obtained in Example 2 was added to methanol (200 ml).
The mixture was dissolved in water, water (50 ml) was added, and the mixture was stirred at room temperature for 2 days. Methanol was removed under reduced pressure and water was decanted from the residue. Water (approximately 100 ml) was added to wash away the gum-like substance adhering to the flask. After repeating this washing operation four times, the gum state was vacuum-dried to obtain γ-[p-(bis-β-chloroethyl)aminophenylureido]propyl polycissesquioxane (2.11 g) as a pink solid. Obtained. Application example 1 Add the γ-(p-sulfamoylphenylureido)propyl polysilsesquioxane obtained in Reference Example 1 to physiological saline (0.85%) containing the surfactant Tween 80 and prepare a specified amount of sample. A suspension containing the following was prepared. The sample solution was mixed with 5 Ehrlichi cancer cells.
Six Swiss mice (male) containing ×10 ⁶ cells were continuously injected intraperitoneally in 0.5 ml doses for 9 days. From the results of the survival effect over 60 days, the mean survival time (MST) was determined, and by comparing it with the mean survival time of the control group (30 animals), T/C% was accurately calculated using a computer. The results are shown in Table 2.

[Table] Application example 2 γ-(p-sulfamoylphenylureido)propyl polysilsesquioxane obtained in Reference example 1 was suspended in a saline solution (0.85%) containing the surfactant Tween 80. A sample solution was prepared so that the dose was 400 mg/Kg. Inject this sample solution into the peritoneal cavity of Walker Carcinoma Sarcoma 256.
Intraperitoneal injections were administered to 6 Sprague-Dawley rats (female) containing 1×10 ⁵ cancer cells for 5 consecutive days, and the survival effect was investigated over a period of 1 month. As a result, the number of survivors out of 6 rats was 2, and the T/C% was 315. Application Example 3 Using γ-[p-(bis-β-chloroethyl)aminophenylureido]propylpolycissesquioxane obtained in Reference Example 2, mice were cultured in the same manner as described in Example 4. An anticancer activity test against Ehrlichi cancer revealed that the dosage
T/C (%) was 144 at 200 mg/Kg. Application example 4 A nutrient medium containing 1.5% agar is sterilized by heating at 121°C for 15 minutes, then cooled to 50°C, and pre-grown bacteria or spores suspended in sterile water are added to it. The mixture was mixed, poured into a shear plate, and solidified into a flat plate. A circular piece of paper with a diameter of 8 mm was immersed in a methanol solution containing about 3% of γ-(p-sulfamoylphenylureido)propyl polysilsesquioxane obtained in Reference Example 1. The excess was removed and placed on a solidified agar medium. about
After culturing at 30°C for 24-48 hours, the diameter of the inhibition zone was measured. As a result, rice blast disease (Pyrichlaria
oryqae), an inhibition circle of 26 mmφ was observed. Application example 5 A sample with a diameter of 8 mm was added to a methanol solution containing 3% of γ-(p-sulfamoylphenylureido)propyltriethoxysilane synthesized in Example 1.
After soaking circular filter paper and removing the excess on filter paper,
The filter paper was soaked in an aqueous hydrochloric acid solution and dried to fix the organosilicon compound on the filter paper. Using the sample filter paper, an antibacterial test against rice blast disease was conducted in the same manner as in Example 4, and the inhibition circle was 24 mmφ.
It was hot.

[Brief explanation of the drawing]

The accompanying drawings FIG. 1 is a chart showing the infrared absorption spectra of the compound obtained in Example 1, and FIG. 2 is a chart showing the infrared absorption spectra of the compound obtained in Example 2.

Claims (1)

[Claims] 1. General formula [However, X is a sulfamoyl group or a bis(β-chloroethyl)amino group, and R is an alkyl group.] A substituted phenylureidopropyltrialkoxysilane.