JPS58222093A - Haloalkylureido group-substituted trialkoxysilane and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula I (R is alkyl; R' is alkylene; X is halogen; n is 1 or 2). EXAMPLE:Chloroethylureido group-substituted trimethoxysilane shown by the formula II. USE:An intermediate for a haloalkylureido group-substituted polysilsesquioxane having improved carcinostatic effect on cancer cells such as Ehrlich ascites carcinoma, ascites carcinoma of Walker carcinosarcoma, leukemia P388, etc. PROCESS:A haloalkyl isocyanate (e.g., beta-chloroethyl isocyanate, etc.) shown by the formula XR'NCO is reacted with an aminoalkyl-trialkoxysilane compound (e.g., gamma-(2-aminoethyl)aminopropyl-trimethoxysilane, etc.) shown by the formula III.

Description

[Detailed description of the invention] The present invention has a general formula.

(RO) a B i CH20Hs CL 4 N
0HICH* f N HON HR'X0=OHHR
Provided are a haloalkylureido group-substituted trialkoxysilane represented by ' It is something.

Conventionally, functional alkyl silane compounds such as 6-amitunrobiltriethoxysilane and functional propylsilane compounds such as he-(glycidyloxy)propyltriethoxysilane have been used as water repellent treatment agents and rust preventive agents for fiber surfaces, etc. It is known that it is used in agents etc. Furthermore, it is obtained by reacting 3-aminopropyltriethoxysilane with an organic isocyanate, and has the general formula (ICtO).
6-(organoureido)propyltriethoxysilane represented by i 5iOH10HtOHINHONHAr (wherein mr represents an organic group) is also US Special Punch No. 29
It is a known compound as shown in No. 07782. 1
However, none of these known documents describes the physiological activity of organosilicon compounds. Ta. As a result, the general formula, (CHnO
) a 810) far; HtOH4(NHOHtOHm
) nN) 1 m (where l = n is an integer represented by 1 or 2) by reacting polyaminoalkyltrimethoxysilane with β-chloroether in cyanate, a new compound with the general formula (where n It was confirmed that a chloroethylureido group-substituted trimethoxysilane represented by the following integer (1 or 2) could be synthesized. Further, the above synthetic studies were continued, and the synthesis of various compounds, their structures and uses were confirmed, and the present invention was completed and provided here. That is, the present invention provides haloalkylureido group-substituted trialkoxy represented by the general formula (wherein, R is an alkyl group, R' is an alkylene group, X is a halogen atom, and n is a number represented by 1 or 2!). It's silane.

Further, the present invention provides a general formula, xR'uco (where R/
is an alkylene group and X is a halogen atom), and a haloalkylinocyanate represented by the general formula, (R
O), sj, aH, OH! 01(Taki -(NHO
Hn CH Also provided is a method for producing a haloalkylureido group-substituted trialkoxy heptadrane.

The haloalkylureido group-substituted trialkoxysilane, which is a novel compound of the present invention, is represented by the general formula (wherein, R is an alkyl group, R' is an alkylene group, X is a halogen atom, and n is an integer represented by 1 or 2). It will be done.

The alkyl group in the above general formula (1) is generally a hydrolyzable alkyl group, since the compound represented by the above general formula 0) is hydrolyzed and used for its purpose as described in 5 below. It can be used without any particular limitations. Generally, lower alkyl groups such as methyl group, ethyl group, zorobyl group, butyl group, etc. are preferably used industrially. Also, the general formula (1)
Like the alkyl group above, the alkylene group in
Six alkylene groups are most preferably used. Further, the halogen atom may be chlorine, bromine, iodine, or fluorine without particular limitation. The properties of the compound represented by the general formula (1) do not change significantly depending on the type of these halogen atoms. Furthermore, n in the general formula (1) is an integer of 1 or 2 due to restrictions depending on the raw materials used when producing the compound represented by the general formula (0).

The haloalkylureido group-substituted trialkoxysilane represented by the above general formula (1) is a very slightly viscous solid at room temperature and pressure when n is 1 in the above general formula (1); In case 2, it is usually solid. Both compounds are extremely hygroscopic, and when left in the air, the moisture in the air turns them into a viscous syrup-like solid. Further, the haloalkylureido group-substituted trialkoxysilane of the present invention is generally prepared by the following formula (0) to ().
It can be confirmed that each compound is represented by 1).

(a) By measuring the infrared Wk yield spectrum (1r), it was found that the ureido group 17' was found near 6R00cm-'.
Absorption based on NH bonds, 2940 an' and 2860
Absorption based on OH bond of alkyl group near Sono 4, 17
Absorption based on the carbonyl bond of the ureido group appears at SO ~ 1620 cm-''.

←) By measuring the mass spectrum (ms) and calculating the composition formula corresponding to each observed peak (generally the mass number expressed as m/θ, which is the ion molecule Jim divided by the number of charges 8), It is possible to estimate the binding mode of the compound subjected to measurement, and ultimately its molecular weight. That is, the general formula (RO) a 810HmOH*OHt (NHOH
*Oshi)nNH! (wherein, R is an alkyl group, n is 1 or 2) (hereinafter simply referred to as polyaminoargylsilane) and the general formula XR'NOO (wherein R' is an alkylene group) , X is a halogen atom) In the products obtained by reacting the haloalkyl isocyanates represented by I2] to 8, peaks exhibiting m/e g larger than that of the corresponding raw material polyaminoalkylsilane. are observed in large numbers. For example, as a raw material, (CHI O)
s 81011* OHa OHa (N HqH*
OHa) When using nIIIs, a/e 12
1 K (aHso), peak corresponding to st■, m/
The strongest peak corresponding to a 51 K OHa 0elC and the strong peak corresponding to c11ρ at m/e15 can be confirmed.

(→ 11 carbon nuclear magnetic resonance spectrum ("c-nmr)
By measuring , it is possible to know the number and types of alkylene groups such as methylene groups, alkyl groups such as methyl groups, carbonyl groups, etc., present in the compound subjected to measurement. Specific examples will be described in more detail in the examples below, but
For example, as the raw material (CHs O)a 810Ht OHt OHa (N
HOH 禦OHt ). By measuring the "O-nmr" of the skeleton product obtained when using HH, and analyzing each peak on cotton 91, the approximate value of each chemical shift is shown in the following general formula, The presence of each peak characteristic of each carbon atom can be confirmed.

) Carbon, hydrogen, nitrogen, halogen,
Determine the weight percent of each silicon, and then calculate the weight percent of each recognized element.
By calculating the sum of 100 and 100, the weight of oxygen can be calculated, and therefore the compositional formula of the compound subjected to measurement can be determined.

On the other hand, as mentioned above, the general formula of the present invention (where R is an alkyl group, W is an alkyref group, and X is a hap
The haloalkylureido group-substituted trialkoxysilane represented by
Colorless mx extremely viscous solid (in the general formula, n is 1)
) or an amorphous solid (when n is 2 in the general formula). However, if the degree of purification is incomplete,
When a purified product is left in the presence of oxygen for a long period of time, it usually becomes pale yellow, yellow, yellow-orange, orange, yellowish brown, or brownish in color depending on the degree of exposure. The haloalkylureido group-substituted triple koxysilane is quite soluble in K such as methanol, ethanol, y,y-dimethylformamide, formamide, dimethyl sulfoxide, etc.; It does not melt very much. In addition, in water or a water-containing solvent, alkoxy of a trialkoxysilane substituted with a haloalkylureido group.

When the group is hydrolyzed, 8l-OH bonds and further 5t-o-'si bonds tend to be produced, and when completely hydrolyzed, organic compounds called polysilsesquioxanes are formed. Provides silicon polymer. The rate of this hydrolysis reaction is significantly accelerated by the presence of a small amount of acid or base in the reaction system. In general, the haloalkylureido group remains unchanged during hydrolysis under normal mild conditions, and It remains in polysilsesquioxane molecules, which are decomposition products.

When the haloalkylureido group ff1i-converted alkoxysilane of the present invention is heated to 120° C. or higher, usually without a solvent or in a solvent, it produces bubbles and decomposes. The decomposition reaction tends to become more intense as the heating temperature becomes higher.

The method for producing the haloalkylureido group-substituted trialkoxysilane of the present invention is not particularly limited, and any method may be used. A representative manufacturing method that is generally suitably employed will be described below. For example, the desired haloalkylureido group-substituted trialkoxysilane can be obtained in good yield by reacting a polyaminoalkylsilane represented by the following formula with a haloalkylisocyanate, preferably under anhydrous conditions. The chemical formula for the above reaction is as follows.

(RO)s 810HM OHx CH@ (NHOH
t CHt ) NH* ” ” ” ” ” The polyaminoalkylsilane represented by the above formula is not limited to its production method, and for example, those obtained by known production methods can be used without particular restriction.

Further, haloalkyl isocyanate can also be used without being limited to its manufacturing method. However, in industrial implementation, restrictions are added to the industrial production of the polyaminoalkylsilane and haloalkylisocyanate, and in the raw materials shown in the reaction formula (I), the alkyl group (6) is generally a lower alkyl group. For example, methyl, ethyl, propyl, and butyl groups are preferably used, and alkylene groups (R'
) is generally preferably an alkylene group having 1 to 6 carbon atoms.

Further, the halogen atom (3) is not particularly limited, and may include chlorine, bromine,
It may be selected from iodine and fluorine as necessary.

In addition to the length, n is an integer of 1 or 2 due to limitations solely from the standpoint of raw materials. Of course, as the alkyl group and alkylene group, groups other than the above-mentioned lower hydrocarbons can be used, so 14
"11"! , 1: L゛′-1"1"1"t*e<
+1i tends to make it difficult to purify the target product.

Representative examples shown by the above reaction formula (It) will be described in detail in the Examples below. Although the reaction can generally be carried out without a solvent, it is generally carried out in the presence of a solvent. The solvent is not particularly limited and can be used as long as it does not react with the raw materials, and generally includes hydrocarbon solvents such as benzene, toluene, and hexane; halogenated hydrocarbon solvents such as chloroform and carbon tetrachloride; dimethyl ether. , ether solvents such as diethyl ether are preferably used.

Further, the conditions of the reaction formula button are not particularly limited. For example, depending on the presence or absence of the solvent or the type of solvent, -CJ4 may be used, but generally at a temperature of -70°C to 120°C.
It is sufficient to select a time in the range of several tens of minutes to 40 hours. In addition, since the reaction pressure is sufficiently low to proceed under atmospheric pressure, it is usually sufficient to carry out the reaction at normal pressure, but it is also possible to carry out the reaction under increased pressure or reduced pressure if necessary.

As is clear from the above reaction formula (1), the amount of haloalkylisocyanate that is lost in the reaction varies depending on the species MK of polyaminoargylsilica/one raw material. That is, when n in the general formula of the polyaminoargylsilane shown in the above reaction formula is 1, 2 equivalents of haloalkylinocyanate are required for the reaction per 1 equivalent of the polyaminoalkylsilane used; When n is 2, 3 equivalents of haloalkyl isocyanate are required for the reaction per 1 equivalent of polyaminoalkyl sila used. Normally, nuclear reactions proceed in a constant manner, so depending on the type of polyaminoalkylsilane used, it is sufficient to use only the stoichiometrically necessary amount of no-roalkylinocyanate. On the other hand, there is no problem even if a small excess or a large excess of /-roalkylisocyanate is used. In such a case, the excess noroargyl isocyanate can be recovered by means of steam trading after the reaction. In addition, the reaction proceeds in the same manner when the amount of the -roalkylisocyanate used is less than the required amount of the polyaminoalkylsilane used, but of course the resulting /-roalkylureido group-substituted trialkoxysilane is It becomes a mixture. The reaction formula in such a case is generally as follows.

(RO)m Si OH* C11* OHμN HO
HtOH! '),, N H (where R is an alkyl group, R' is an alkylene group, X is a halogen atom, n is an integer represented by 1 or 2, and a is the number of moles of the haloalkylisocyanate used. y is x〉0.7〉
0 and X + 7: a. ) After the completion of the reaction, the trialkoxysilanes substituted with no-roargylureido groups produced under the above-mentioned reaction conditions can be removed by distillation to remove excess i.
When a loalkylisocyanate is used, KJIi can be separated very easily by distilling off the 7% u alkyl inocyanate remaining after the reaction together with the solvent. As the distillation means, in addition to normal pressure distillation, means such as reduced pressure distillation and vacuum distillation are preferably used. When an excess of haloalkylinocyanate is used in the reaction, or when a solvent with a relatively high boiling point such as N,N-dimethylformamide or diethylene glycol dimethyl ether is used, the target compound, the no-loalkylureido group, is removed during distillation. In order to prevent thermal decomposition of the substituted trialkoxysilane and to obtain the desired product in a more pure manner, it is desirable to perform distillation under reduced pressure or vacuum distillation. Furthermore, depending on the type of solvent, for example, in the case of hexa/etc., only the desired product becomes an insoluble solid and precipitates, so it can be easily isolated by removing the solvent etc. at an angle. . The trialkoxysilane substituted with a 7-roalkylureido group of the present invention isolated by the above-described procedure is 1[extremely pure, but when a 7-roalkylureido group-substituted trialkoxysilane of even higher purity is required. For this purpose, methods such as recrystallization, column chromatography, and reprecipitation are used.
1.

The p-alkylureido-substituted trialkoxysilane of the present invention contains a trialkoxysilyl group in its molecule that is susceptible to dehydration condensation through hydrolysis. When hydrolyzed with inorganic compounds, various dehydration condensation products are obtained.

Therefore, by applying this property, it can be used as a coating material that changes the surface condition of paper, wood, fiber cloth, glass, etc. Further, the no-roalkylureido group-substituted trialkoxysilane of the present invention is hydrolyzed alone or with other hydrolysis w! under mild conditions. When hydrolyzed together with a monopolymerizable compound, it becomes a no-roalkylureido group-substituted polysilsesquioxane or its rust conductor. The polysilsesquioxane with a base of no-roalkylureido obtained by this hydrolysis has excellent physiological activity, as is clear from the application examples described below, and is particularly effective against Ehrlich ascites carcinoma in mice and Walker cardiac carcinoma. It exhibits excellent anticancer effects on cancer cells such as sarcoma ascites cancer and P38B leukemia cancer. As described above, trialkoxysilanes substituted with no\roalkylureido groups are extremely useful new compounds that can be used in a wide variety of applications.

The present invention will be explained in more detail with reference to the following examples and application examples, but the present invention is not limited to these examples and application examples.

Example 1 Distilled f# prepared r-(2-aminoethyl)aminopropyltrimethoxysilane (10,09i1.0.045
m01e) in anhydrous hexane (20tj)) and β-chloroether inocyanate (10,5077,0
, 99 mole) was added dropwise while cooling with ice, a violent reaction started immediately.

After completion of the dropwise addition, the mixture was stirred at room temperature, the solvent and excess β-chloroethyl isocyanate were removed by distillation under reduced pressure, and the residue was vacuum-dried to obtain a translucent starch syrup-like solid (19.50 g). Ta. When we measured the infrared absorption spectrum by applying it to a potassium bromide plate, we found that
Broad absorption based on the NH bond of the ureido group at 3320 Kuni-1, absorption based on the OH bond of the alkyl group at 2940 Sonoku and 2860 cm-', and absorption based on the OH bond of the alkyl group at 1680 cm' and 1
650cIa-' K Absorption based on the ureido group nocarbonyl bond was observed.

When the quality spectrum was measured, a peak corresponding to rn/e 165 (OHsO)msiOHx'), m/
e121 K (OHsO) asieK showed a strong peak corresponding to O'H・0■ at m/e 31, and each peak corresponding to yr/e 151c CHi'.

In addition, its elemental analysis value is 037.47%XN7゜5゛6
%, N12.58chi, ON 16.881% BL7
．． 02% and composition formula CIa Hsol'140g0
Calculated value tare 60 for 1tSi (463,41)K
! 8.79chi, H6, 98%, N12.93%, c1
16. N6chi, E116.48- matched. Further I
When the j□-nuclear magnetic resonance spectrum (δ, ppm: based on tetramethylsilane) was measured in methanol, the analysis results were as follows.

From the above results, it was revealed that the isolated product was chloroethylureido group fIIt-substituted trimethoxysilane represented by the following formula.The yield is the r-(2-aminoether)aminopropyltrimethoxysilane used. against 10
It was 0chi.

11 Example 2 Distilled flVM r-(2-(ethylenediamino)ethyl]aminoprobyltrimethoxycin (9,5411
0,036moxe) was dissolved in anhydrous ether (20m/), cooled in a dry ice bath, and β
-chloroethyl isocyanate) (11,40J/,
0.108LIIo1θ) in anhydrous ether (201
/) was added dropwise. As the reaction progressed, a viscous solid was first formed. After the dropwise addition was completed, the reaction mixture was continued to be stirred at room temperature for 6 days, and the solution turned yellow and a large amount of white solid was produced. By decanting the solvent and washing the residue several times with anhydrous ether (1QR1), a white solid (20,96,9) was obtained by vacuum drying the residue. When the infrared absorption spectrum was measured by preparing potassium bromide tablets, it was found that NH of ureido group at 3526α-1
Broad absorption based on bonds, 2940-″ and 2825
Absorption based on OH bond of alkyl group at n-', 16
60cm-' and 162QCi! 'An absorption based on the carbonyl bond of the ureido group was observed. Mass spectrometry measurements revealed that (OHaO)sS was found at m/e 149.
i O right OH @ le corresponding peak, // 5th (C
几o), SURHIK compatible with stoki, m/e 121
d((iHsO)a81eK corresponding peak, a/e
31 shows a strong peak corresponding to cH and oΦ, and m/e15 shows a strong peak corresponding to OH. In addition, its elemental analysis value is 059.87%,
N7. IQ'lA, Mi4.69'16.0119, O
is%, 815.24% Teatte composition formula C1,H
,. N, 0.01. Calculated value for Si (s 82.01) c 69.21%% H6,75
%z ”14.44%, ax18.28chi, 514.8
It matched 5%. Furthermore, when the l5C-nuclear magnetic resonance spectrum was measured in methanol, there was a peak at 49.5 ppm based on the methyl carbon of the methoxysilyl group, and a peak at 6.3 ppm.
pm is a peak based on the carbon of the methylene group directly connected to the silicon atom, 22.2 ppnl is the peak based on the carbon of the methylene group adjacent to the methylene group directly connected to the silicon atom, 1
59.21) Pms 160. Q ppm and 162
It showed various characteristic peaks such as beers based on the carbonyl carbon of the ureido group of ppmK6PJl.

From the above results, it was revealed that the isolated product was a chloroethylureido group-substituted trimethoxysilane represented by the following formula. Yield i! r-(2-(ethylenediamino)ethyl)aminozolobyltrimethoxysila/100%.

1 Example 6 Distilled γ-(2-aminoethyl)aminozorobyltrimethoxysilane (8,89#).

04 moxe) to dimethoxyethane (xomj
), and while cooling with ice water, β-chloroether isocyanate (5,28N, 0.05 mole
) was added dropwise. After the dropwise addition was completed, the solvent was distilled off under reduced pressure to obtain a viscous starch syrup-like solid (14, 15#). Elemental analysis of the product revealed that it was 040.0! ichi, H7
, 81%, NI LO6chi, al 12.44%, sl
y, a s qbttl value*, and the compositional formula was calculated as C1t75H2ZONL250t2501125''.In addition, when the infrared absorption spectrum and mass spectrum were measured, the infrared absorption spectrum and mass of the product obtained in Example 1 were obtained. The spectrum was almost the same.

Furthermore, when the 1IC-nuclear magnetic resonance spectrum was measured, it showed a spectrum that was almost the same as that of the product obtained in Example 1, but the intensity of each peak based on the three types of carbon bonds of the chloroethyl ureido group was different from that in Example 1. It was confirmed that the intensity of each peak based on the 61 & carbon bond of the couloetherureido group of the product obtained in 1 was about 80-. From the above results, the product is determined by the amount of r-(2-aminoether)aminoprobyltrimethoxine used and the total amount of β-ri...-thyl isocyanate added to the reaction, , 1
It was revealed that the mixture was a mixture represented by the following general formula.

(cHmo)sstaHIcamcH,Ncn,cH*
IJa-(-La嘱cu*a1).

Example 4 r-(2-aminoethel)aminozorobyltriethoxysilane (8,55p) manufactured by X[M.

0,0 S mole) β-chlorop-ethyl isocyanate) (io, 55 g,
o, inole) in anhydrous benzene solution (zolIL
1) was added dropwise to the ice water coating. After completion of the dropwise addition, the mixture was left at room temperature overnight and heated to 50°C on an oil bath for 1 hour.

Volatile components were removed by vacuum distillation, and the residue was dried in vacuum to obtain a pale yellowish brown solid (14, 22, f). When the infrared absorption spectrum was measured, there was a wide range at 3620α-1 due to the NH bond of the ureido group. Absorption, 2940ch
CH of the alkyl group at t' and 2825 cIIL-'
Based on the bond (absorption, 1680 cuz-” and 1650
Absorption based on the carbonyl bond of the ureido group was observed in ctn-'.

The mass spectrum was measured as m/θ162IΦ (ltO), a peak corresponding to Eii was observed.

In addition, its elemental analysis values are 04LO1chi, H7゜88man,
N12.11%chi, OX zs, ao*, st6.64
% and has a compositional formula of C0, N40. C1,81 (476
, 49) is the calculated value of 042.85chi, H7,
62 buns, N11.76chi, 0114.88chi, st6.
Comparing the measurement results of L Tarosa 6 K" O-Nuclear Magnetic Resonance Spectrum ("O-nmr) with the "O-nmr" of the chloroethylureido group-substituted trimethoxysilane obtained in Example 1. , almost the same peaks except that the peak at 49°5 ppm due to the carbon of the methoxy group disappears, and peaks at 19.1 ppm and 59.0 ppm due to two types of carbon in the methoxy group appear instead. showed that.

From the above results, it was revealed that the isolated product was a chloroethylureido group-substituted triethoxysilane represented by the following formula.

I (Ckb CHa O)s 81ons 01lt O
Ht N OHa CHa N HON HCHa O
H+ 0NQ=Q NHOH,OH,01 Example 5 γ-(2-aminoethyl)aminopropyltri(n-propoxy)silane (6,41#.

0.02 mole) was dissolved in anhydrous N,N-dimethylformamide (3 oml) and heated to -20°C in a dry ice bath.
Fluoromethyl isocyanate) (7,5
1j+, 0.10 mole) was added under stirring to react. After the reaction was completed, volatile components were removed by distillation under reduced pressure to obtain a translucent solid (15,04,9). The product was subjected to instrumental analysis and elemental analysis in the same manner as in Example 1, and it was confirmed that the product was fluoromethylfried group-substituted tri(n-propoxy) 7rane represented by the following formula.

(CHa CHa OHt O)a Si CHa
OHt OHa N OHt CHz N HCN H
OHm F0=CNHOH*F The yield was 97.5% based on the γ-(2-aminoethyl)aminopropyltri(n-propoxy)silane used.

Reference Example 1 Chloroetherureido group-substituted trimethoxysilane (18,4M, !il) obtained in Example 1 and represented by the following formula
Methanol 1 (OHa O)s 810Ht OHt CHa N
01lt Oklm N HONH01(t OHt
By dissolving the mixture in C10x ONHCHa CHz 01 (20t/), adding water (50at) and stirring at room temperature for 6 days, a chloroetherureido group-displaced polysilsesquioxane (hereinafter referred to as Don: UP80) represented by the following general formula was obtained. O 1 0 810HIC obtained as a very pale cream-colored congener! HtOHtNO11tOHIN
H(ENHCH Minoh 0HtO'l
'LJ5 ■ 0=ONHCHa CHa OX (Hereinafter, this compound will be abbreviated as DonUP80) Reference Example 2 The chloroethylureido group-substituted trimethoxysilane (17,48,9) shown by the following formula obtained in Example 2 was dissolved in methanol. (80t/) 0=ONHOH Dissolved in C11,01 1 Further water (20ad) was added and stirred at room temperature for one day.
UPSO) was obtained as a tan solid.

0-ONHCH,OH,O'1 Application example 1 Add ncgupso obtained in reference example 1 and TOEUI'EIO obtained in habit example 2 to physiological saline to prepare sample WI solution containing a specified amount of sample. Created. The nuclear sample was transferred to a CD containing 1 x 100 Ehrlich cancer cells. , mouse (
The drug was administered by intraperitoneal injection for 0.5 days each for 9 days to 6 females (female). From the results of the 60-day survival effect test, the mean survival days (MST) was calculated and compared with the mean survival days of the control group (30 animals) to accurately calculate 'r,'o qA using a computer. . That is, the average survival days (T) of the test subjects and the average survival days (0) of the control subjects were determined by this test, and T10 was calculated by T/cx10G (S). The results are shown in $1. Note that 60 mice were used as a control group, and the average value for 6 mice is shown in the table.

Application example 2 below: DOKUPSO and TOEU, which are chloroethylureido group-substituted polysilsesquioxanes obtained in Reference examples 1 and 2.
Treatment of carcinoma 7 and sarcoma 2 using PBO
An anticancer activity test against s6 ascites H was conducted.

That is, a sample solution containing a specified amount of sample was prepared for each polysilsesquioxane by the method described in Example 1. These sample solutions were intraperitoneally injected for 5 consecutive days into 6 Sprague-Dawley rats (male) that had I x 10' Walker Cardiosarcoma 256 cancer cells in their peritoneal cavities. The survival effect was investigated over a period of days, and the average survival days (M8T) was determined. T/C% was calculated by comparing the average survival days with that of the control group (60 animals). The result is DOBUPS00
In the case of 1.1' administration at 12.5 mti/9 K, T10 (饅) was 685 or more, and surprisingly, all of the rats (6 rats) subjected to the life extension test survived.

In the case of DOBUPSO, the dosing lid 26
At m97Kg, T/c (%) showed a value of 137.

Application example 6 DCEupso, which is a chloroethylureido group-substituted polysilsesquioxane obtained in Reference Examples 1 and 2
A sample solution containing a specified amount of sample was prepared using the method described in Example 1 for FiUP80. The sample solution was
588! Intraperitoneally of 0406 ODF, line mice with a number of I x 10'1 J.P. leukemia cancer cells -0,
5 injections were administered continuously for 9 days. After investigating the life extension effect test over 60 days fC, in the case of DOKUPSO,
Administration ii: T/C (*) is 150 at 50 m177Kg, administration lid 50 mJ in case of TOFiUP80,
T10 (*) showed a value of 136 in %〇%
Kende Applicant: Yamakotatsu Co., Ltd.

Claims (1)

[Scope of Claims] 1, Ell-1R, 2, 2, 1,...
78, X is a halogen atom, and n is an integer represented by 1 or 2). hmm. (2) A haloalkyl isocyanate represented by the general formula xn'xco (where R' is a group at 7 and
810H* CHl CHl-4NHOH*OH*)
HNH is an alkyl group, R' is an alkylene group, X is a halogen atom, and n is an integer of 1 or 2).