JPH0326699B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a polysilsesquioxane having a novel structural unit and an anticancer agent containing the polysilsesquioxane as an active ingredient. Conventionally, some polysilsesquioxanes are (−
The repeating unit is silsesquioxane represented by O-) ₃ (-SiR) ₂ or O _{1 .5} SiR (where R represents a monovalent organic group), and the model is as follows: It is known to be a polymer compound that generally has a ladder-like or cage-like skeleton structure, and is widely used as a water repellent agent, lubricant, catalyst, synthetic intermediate for organosilicon compounds, etc. . On the other hand, as an organosilicon compound having a carbon-nitrogen double bond, in US Pat. No. 3,022,270,
general formula, (However, R ₃ is a hydrocarbon group or a hydrogen atom, and a is 3
or more, b is an integer of 0 to 3, R is pyridine,
Heterocycles such as indole, acridine, piperidine, quinoline, furan, benzofuran, pyran, pyrimidine, cinnoline, quinazoline, phenazine, pyrazole, oxazine, benzoxazine, oxazole, isoxazole, etc.
Alkoxysilane derivatives and polysiloxane derivatives in which the unsaturated valence of the silicon atom represented by si≡ is bonded to alkyl, allyl, alkoxy, hydroxy, or -O-Si≡ group are known. The use of this compound as a filtering agent, an ultraviolet absorber, and a scissoring agent has been proposed. The present inventor has synthesized various polysilsesquioxanes and conducted various studies on their physiological activities. As a result, it was discovered that polysilsesquioxane of the following general formula has excellent physiological activity, and the present invention was completed. That is, the present invention provides the general formula, [In the formula, Ar is

[Formula] or

[Formula], R ₁ and R ₂ are each a hydrogen atom; an alkyl group; a halogen atom; a phenyl group; an alkoxy group; an alkylcarbonyl group; an alkoxycarbonyl group; a carbamide group; a carboxy group or a salt thereof; a sulfonic acid group or its salt; nitro group; cyano group or

A group represented by [Formula], which is a ring-closed group bonded to the 2nd and 3rd carbon atoms of a furan ring or thiophene ring (however, when R ₁ or R ₂ is a hydrogen atom or an alkyl group, other groups i.e. R ₂ or
R ₁ is a hydrogen atom or the above-mentioned substituent other than an alkyl group. The polysilsesquioxane of the present invention is a new compound having a structural unit represented by the above general formula,
In the general formula, an alkyl group represented by R ₁ or R ₂ ,
Alkoxy groups, alkylcarbonyl groups, and aliphatic hydrocarbon residues contained in alkoxycarbonyl groups are not particularly limited and can be used, but generally those with 1 to 4 carbon atoms, such as methoxy groups, ethoxy groups, Propoxy group, butoxy group, acetyl group, ethylcarbonyl group, propylcarbonyl group, butylcarbonyl group, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, methyl group, ethyl group, n-propyl group, iso- Propyl group, n-butyl group, iso-butyl group, t-butyl group, etc. are most preferably used because of their advantages in manufacturing process. Further, in the above general formula, the halogen atom represented by R ₁ or R ₂ includes chlorine, bromine, iodine, and fluorine atoms without particular limitation. Further, in the above general formula, the carboxyl group salt type group and the sulfonic acid group salt type group represented by R ₁ or R ₂ are generally COO M and SO ₃ M, respectively.
M is not particularly limited, but generally includes ammonium (NH ₄ ); alkali metals such as sodium (Na), potassium (K), and lithium (Li); magnesium 1/
Alkaline earth metals such as 2Mg ² ) and calcium (1/2Ca ² ) are most preferably used. Furthermore, in the general formula, R ₁ or R ₂ is

In the group represented by the formula, the ring-closed group bonded to the 2nd and 3rd carbon atoms of the furan ring or thiophene ring is specifically shown by the following general formula.

[Formula] or

【formula】 (However, R is

A group represented by R ₁ or R ₂ other than the group represented by [Formula]. ) Furthermore, in the above general formula, when R ₁ or R ₂ is a hydrogen atom or an alkyl group, another group, that is, R ₂ or R ₁
must be the above atoms or groups other than hydrogen atoms and alkyl groups. Since the physiological activity of the present invention differs depending on each of these atoms or groups, it is sufficient to confirm the physiological activity as necessary and decide in advance which group to use. The polysilsesquioxane represented by the above general formula is amorphous white, pale yellow, yellow, orange-yellow, orange,
It is obtained as a solid polymer exhibiting orange-red, red, brown, blackish-brown colors, etc., and is often crushed and handled as a powder, but depending on the type of Ar in the above general formula, it can be a rubbery solid or a viscous substance. In some cases, it can be obtained as The polysilsesquioxane usually exists as a 3- to 15-mer of the above-mentioned structural units, and is estimated to be a three-dimensional cage-like polymer as described above based on the model of mainly 7- to 8-mers, and is usually composed of ligroin, cyclo It is almost insoluble in pentane and hexane, and is often difficult to dissolve in benzene, toluene, chloroform, carbon tetrachloride, etc. On the other hand, it is soluble in alcohol, and is often soluble in polar non-aqueous solvents such as formamide, N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoamide, etc., and its solubility decreases particularly when heated. There is a tendency for the number to increase significantly. In addition, many substances are poorly soluble in water, and are therefore relatively stable in water, but in acidic or alkaline aqueous solutions, stability varies depending on the concentration and temperature, but in general carbon-nitrogen 2 The heavy bond undergoes hydrolysis, resulting in γ-aminopropyl polysilsesquioxane and corresponding aldehyde compounds (such as substituted furfural or substituted thiophene aldehyde)
Decompose into. The hydrolysis tends to become more severe as the concentration of acid or base increases and as the temperature rises. It can generally be confirmed by chemical analysis and instrumental analysis that the polysilsesquioxane has a chemical structure having a structural unit represented by the above general formula. In particular, elemental analysis and infrared absorption spectrometry are extremely effective methods. That is, the synthesized polysilsesquioxane contains carbon, hydrogen, nitrogen, silicon (and halogen atoms, sulfur atoms, and even metal atoms when the molecule contains halogen atoms, sulfur atoms, and metal atoms). By finding the weight percent of the element and further subtracting the sum of the weight percent of each recognized element from 100,
By calculating the weight percent of the oxygen element, the compositional formula of the polysilsesquioxane sample can be determined. Furthermore, by measuring the infrared absorption spectrum of the sample, it is possible to confirm the characteristic chemical bonds and types of functional groups present within the polysilsesquioxane molecule. In general, the polysilsesquioxane exhibits characteristic infrared absorption based on CH=N bonds in the vicinity of 1650 cm ^-1 to 1620 cm ^-1 , and elemental analysis results indicate that the polysilsesquioxane is in a solid state. It is known that it usually exists in a monohydrated form, sometimes in a dihydrated form, and rarely in an anhydrated form. Furthermore, if the obtained polysilsesquioxane has sufficient solubility in an appropriate solvent to be subjected to measurement, it can be determined by measuring ¹³ C-nuclear magnetic resonance spectrum ( ¹³ C-nmr). It is possible to know the number of carbon atoms in the compound, the arrangement of carbon chains, and the bonding manner of carbon atoms. For example, N-(4-bromothiophenemethylidene)γ
-Aminopropylpolysilsesquioxane in benzene, based on tetramethylsilane
When measuring ¹³ C-nmr, each peak observed is analyzed as follows (unit: δ, ppm). Furthermore, ¹ H-nuclear magnetic resonance spectrum ( ¹ H
-nmr), it is possible to know the bonding mode of hydrogen atoms present in the compound of the present invention represented by the above general formula. For example, N-(4-
When ¹ H-nmr of (bromothiophenemethylidene) r-aminopropylpolysilsesquioxane is measured in benzene using tetramethylsilane as an internal standard, each peak observed is analyzed as follows (unit: δ, ppm). The method for producing the polysilsesquioxane used in the present invention is not particularly limited, and any method may be used to produce the polysilsesquioxane. Generally, it can be easily synthesized by dehydrating condensation of γ-aminopropylpolysilsesquioxane and an aldehyde compound represented by the general formula Ar-CH=O, as shown in the general reaction formula below. O _1.5 SiCH ₂ CH _{2 CH 2} NH ₂ +Ar−CH ₌ O →O _1.5 SiCH ₂ CH ₂ CH ₂ N=CH−Ar [In the formula, Ar is

[Formula] or

[Formula], R ₁ and R ₂ are each a hydrogen atom; an alkyl group; a halogen atom; a phenyl group; an alkoxy group; an alkylcarbonyl group; an alkoxycarbonyl group; a carbamide group; a carboxyl group or a salt thereof; a sulfonic acid group or its salt; nitro group; cyano group or

A group represented by [Formula], which is a ring-closed group bonded to the 2nd and 3rd carbon atoms of a furan ring or thiophene ring (however, when R ₁ or R ₂ is a hydrogen atom or an alkyl group, other groups i.e. R ₂
or R ₁ is the above-mentioned substituent other than a hydrogen atom or an alkyl group). ] The molar ratio of the aminopropyl polysilsesquioxanes and the aldehyde compound during the reaction is not particularly limited, but in consideration of recovery of unreacted materials, the molar ratio should be 1:1 or more, and the aldehyde compound should not be used in excess. Good to use. Unreacted carbonyl compounds may be removed by distillation after the reaction and washing with a solvent such as hexane. In addition, it is generally preferable to use a reaction solvent in the above reaction, and for example, solvents that are azeotropic with water such as benzene, toluene, chloroform, and ethanol can be suitably used. Although the reaction temperature can be varied over a wide range of, for example, 0 to 150°C or higher, it is generally preferable to carry out the reaction at the boiling point temperature of the solvent. Although the reaction time varies depending on the reaction temperature, it can generally be selected from several minutes to several days. In order to promote the dehydration condensation reaction in the above reaction, a method of adding an acid such as acetic acid or formic acid to the reaction system is often suitably employed. The polysilsesquioxane of the present invention represented by the above general formula is a new compound, and when the present inventor conducted a physiological activity test on the polysilsesquioxane, it was confirmed that the polysilsesquioxane has particularly remarkable anticancer activity. . That is, since the polysilsesquioxane exhibits an extremely strong anticancer effect, the polysilsesquioxane having the above-mentioned structural unit can be used as an anticancer agent for the prevention, treatment, or treatment of various cancers. Therefore, the anticancer agent of the present invention can be administered to patients orally, parenterally (for example, intraperitoneally, intrarectally), or locally, and the effectiveness of polysilsesquioxane, the active ingredient, The dosage varies depending on the patient's age, weight, severity of symptoms, type of cancer, etc., but in general, 800
~0.002mg/Kg/day, preferably 500~0.01mg/
It can be Kg/day. The daily dose is 1
It can be administered only once a day or divided into several times (3 to 5 times) a day. In addition, the above dosages are only a guideline and are subject to the judgment of the treating physician.
It goes without saying that it is also possible to administer doses exceeding the above range. When administering the active ingredient, the polysilsesquioxane 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 tablets, pills, sugar-coated tablets, powder packets, granules, syrups, capsules, etc., and for parenteral administration, it can be formulated into suspensions, suppositories, etc. Furthermore, for topical administration, it can be formulated into dosage forms such as ointments, plasters, and creams. The concentration of the active ingredient in these preparations is not particularly limited and can vary widely depending on the dosage form, but it is generally about 0.05 to 90% by weight, preferably 1 to 60% by weight. be able to. As excipients that can be used in the above formulation, any excipient commonly used in the field can be used, and for solid form formulations, for example, lactose,
Examples include sucrose, starch, glycine, crystalline cellulose, mannitrate, magnesium stearate, liquid paraffin, calcium carbonate, sodium hydrogen carbonate, etc. For liquid form preparations,
For example, physiological saline, surfactant solution, glucose solution,
Examples include alcohols and esters. Specific examples of such formulations are as follows. Formulation Example 1: Capsule 0.6 parts by weight of magnesium stearate and 4.5 parts by weight of lactose
Add parts by weight and stir and mix to make the mixture uniform.Furthermore, 5 parts by weight of lactose and 10 parts by weight of crystalline cellulose are added and mixed. 20 parts by weight of polysilsesquioxane, which had been previously pulverized, was added to this mixture.
A prepared powder is obtained by mixing again. Capsules may be produced by filling this powder into gelatin capsules using a capsule filling machine. Formulation Example 2: Ointment After heating and dissolving 10 parts by weight of stearyl alcohol, 20 parts by weight of liquid paraffin, and 160 parts by weight of petrolatum, 0.5 parts by weight of cholesterol and 10 parts by weight of polysilsesquioxane, which had been pulverized in advance, were added. It is preferable to add the mixture with good stirring, and after further stirring, leave it at room temperature to obtain an appropriate hardness. Formulation Example 3: Tablet 25 parts by weight of polysilsesquioxane and mannite
After thoroughly mixing and pulverizing 20 parts by weight, 4.7 parts by weight of potato starch was added as starch paste and granulated. The particles are passed through a 60-mesh sieve, dried to a predetermined weight, and passed through a 16-mesh sieve. Next, the particles may be mixed with 0.3 parts by weight of magnesium stearate, smoothed, and compressed using a tablet machine in a conventional manner to form uncoated tablets of an appropriate size. Examples of the production of polysilsesquioxane used as an active ingredient in the anticancer agent of the present invention, as well as pharmacological activity testing methods and their results are shown below. However, the present invention is not limited to the following examples. Example 1 γ-aminopropyl polysilsesquioxane
A mixture of monohydrate (2.57 g), 5-bromofurfural (5.00 g), and anhydrous benzene (30 ml) was stirred at room temperature overnight, and then heated under reflux for about 5 hours to terminate the reaction while performing azeotropic dehydration. I let it happen. The reaction solution was concentrated, the solid was collected by filtration, washed with benzene, and vacuum dried to give a blackish brown powder (4.72
g) was obtained. Elemental analysis revealed C339.2
%, H4.28%, N5.37%, and C ₈ H ₉ NO ₂ .
Calculated value C33.69% for ₅ BrSi.H ₂ O (285.19),
It was in good agreement with H3.89% and N4.91%. Furthermore, when an infrared absorption spectrum was measured, the infrared absorption spectrum shown in FIG. 1 was obtained. As is clear from Figure 1, no absorption peculiar to the raw material 5-bromofurfural was observed; absorption based on hydration water at 3620 to 3100 cm ^-1 , absorption based on CH=N bond at 1670 cm ^-1 , And absorption based on strong Si-O bond was observed in the range from 1220 to 820 cm ^-1 . From the above results, the isolated product is a Schiff base compound obtained by dehydration condensation reaction, namely N-(5-bromofurylmethylidene).
It became clear that it was γ-aminopropyl polysilsesquioxane. The molecular weight of the product was determined to be 2350 by vapor pressure osmometry (tetrahydrofuran solution). Example 2 γ-aminopropyl polysilsesquioxane Γ
A mixture of monohydrate (4.62 g), 5-nitrofurfural (5.10 g), acetic acid (16.90 g), and benzene (50 ml) was stirred at room temperature for 3 days, and then azeotropically dehydrated by heating under reflux for about 4 hours. The reaction was terminated while After the volatile components were distilled off under reduced pressure, the residue was dried in vacuo to obtain a dark brown powder (8.90 g). Elemental analysis revealed C40.06%, H4.47%,
It shows a value of N11.01%, C ₈ H ₉ N ₂ O ₄ . ₅ SiΓ1/2H ₂ O
Calculated value for (242.27) C39.66%, H4.16%,
It matched well with N11.57%. Furthermore, when an infrared absorption spectrum was measured, the infrared absorption spectrum shown in FIG. 2 was obtained. As is clear from Figure 2
Absorption based on hydration water near 3320cm ^-1 , 1650cm
^-1 Absorption based on CH=N bond and 1220 to 950 cm ^-1
showed absorption based on strong Si-O bonds. From the above results, it was revealed that the isolated product was N-(5-nitrofurylmethylidene)γ-aminopropylpolysilsesquioxane obtained by a dehydration condensation reaction. The molecular weight of the product was measured in the same manner as in Example 1 and was found to be 1590. Example 3 Sodium 5-formylfuran-2-sulfonate (5.15 g) was dehydrated by heating under reflux in benzene (100 ml). The mixture contains γ-
Aminopropylpolysilsesquioxane monohydrate (4.62 g), N,N-dimethylformamide (30 ml), and acetic acid (4.77 g) were added, and the mixture was heated under reflux for an additional 5 days to perform azeotropic dehydration. . A light brown powder (7.10 g) was obtained by suction filtration of the reaction solution. Elemental analysis revealed C31.27%,
The values are 4.72% H, 5.19% N, and C ₈ H ₉ NO ₅ .
₅ Calculated value C31.16 for SNaSiΓH ₂ O (308.34)
%, H3.60%, N4.54%. Furthermore, when an infrared absorption spectrum was measured, the infrared absorption spectrum shown in FIG. 3 was obtained. As is clear from Figure 3, there is absorption based on hydration water near 3540 to 3400 cm ^-1 , absorption based on CH=N bond at 1670 cm ^-1 , and
Strong absorption based on Si-O was observed at 1280 to 960 cm ^-1 . From the above results, it was revealed that the isolated product was N-(5-sodeiosulfofurylmethyldene)γ-aminopropylpolysilsesquioxane obtained by the dehydration condensation reaction. The molecular weight of the product was measured in the same manner as in Example 1 and was found to be 3700. Example 4 γ-Aminopropylpolysilsesquioxane Γ
Monohydrate (1.22g), 5-methoxythiophene-
2-aldehyde (1.33g), anhydrous benzene (30ml)
A dehydration reaction was carried out by heating the mixture under reflux. Benzene was distilled off, and the residue was vacuum-dried to obtain an orange-red rubbery solid (2.34 g). Elemental analysis revealed C42.42%,
The values are 5.20% H, 5.27% N, and C ₉ H ₁₂ NO ₂ .
₅ Calculated value for SSiΓH ₂ O (252.37)
It matched well with C42.83%, H5.59%, and N5.55%.
Furthermore, when we measured the infrared absorption spectrum, the fourth
The infrared absorption spectrum shown in the figure was obtained. As is clear from Figure 4, absorption based on hydration water is present at 3640 to 3200 cm ^-1 , absorption based on CH=N bond is observed at 1630 cm ^-1 ,
It also showed absorption based on Si-O bonds at 1270 to 900 cm ^-1 . From the above results, it is clear that the isolated product is a monohydrate of N-(5-methoxythiophenemethylidene)γ-aminopropylpolysilsesquioxane obtained by a dehydration condensation reaction. Summer. The molecular weight of the product was measured in the same manner as in Example 1 and was found to be 1300. Example 5 γ-aminopropyl polysilsesquioxane Γ
Monohydrate (1.84g) and 4-bromothiophene-2
- An almost white solid (3.17
g) was obtained. Elemental analysis revealed that C32.38
%, H3.18%, N4.62%, Br27.14%, S10.55%,
Showing a value of Si10.02%, C ₈ H ₇ NO ₁ . ₅ BrSSiΓ1/2
C32.88%, which is the calculated value for H ₂ O (292.25),
H3.45%, N4.79%, Br27.35%, S10.97%,
It matched well with Si9.61%. When the infrared absorption spectrum was measured, the spectrum shown in FIG. 5 was obtained. As is clear from Figure 5, there is an absorption based on hydration water at 3600 to 3160 cm ^-1 , an absorption based on CH=N bond at 1630 cm ^-1 , and an absorption based on Si-O bond at 1270 to 900 cm ^-1 . Ta. Furthermore, ¹³ C-nuclear magnetic resonance spectra ( ¹³ C-nmr) (δ, ppm; based on tetramethylsilane) and ¹ H-nuclear magnetic resonance spectra ( ¹ H-nmr) (δ, ppm; based on tetramethylsilane) were analyzed for benzene. The results of analysis of each peak obtained were as follows. From the above results, it was revealed that the isolated product was a monohydrate of N-(4-bromothiophenemethylidene)γ-aminopropylpolysilsesquioxane. The molecular weight of the product was measured in the same manner as in Example 1 and was found to be 2,620. Example 6 The polysilsesquioxanes listed in Table 1 were synthesized by methods similar to those described in detail in Examples 1-5. In Table 1, the mode of each synthesized polysilsesquioxane compound, characteristic absorption value in infrared absorption spectrum and elemental analysis results, as well as the composition of the reaction raw materials used, reaction conditions, and reaction treatment conditions are also abbreviated. . In this example, the molecular weights of polysilsesquioxanes No. 6 and No. 18 were measured in the same manner as in Example 1.
They were 5700 and 2920 respectively.

【table】

【table】

【table】

【table】

【table】

[Table] Example 7 N-(5-bromofurylmethylidene)γ-aminopropylpolysilsesquioxane obtained in Example 1 was added to physiological saline containing surfactant Tween 80, and a specified amount of sample was added. Six types of sample solutions (2512mg/Kg, 1995mg/Kg, 1585mg/Kg,
1259mg/Kg, 1000mg/Kg and 794mg/Kg). Using this sample solution, weigh 20g.
The drug was administered intraperitoneally to 6 female CDF ₁ strain mice before and after the test for 20 days.The acute toxicity value was determined by the method of Richfield and Wilcoxon, and the LD ₅₀ was 2225 mg/Kg. . Example 8 Using the N-(5-bromofurylmethylidene)γ-aminopropylpolysilsesquioxane obtained in Example 1, the anticancer activity against Ehrlichi's ascites carcinoma in mice was tested. That is, an injection prepared from the polysilsesquioxane by the method described in Example 1 was administered to Ehrlichi cancer cells of 5×10 ⁶
Intraperitoneally of 6 Swiss mice (male) with
Continuous injections of 0.5 ml were administered for 9 days. From the results of the survival effect over 60 days, the mean survival days (MST) was determined, and T/C (%) was calculated by comparing it with the mean survival days of the control group (30 animals).
That is, the average survival days were determined for the test subject (T) and the control subject (C), and calculated as T/C x 100 (%). The approximate value is calculated by taking the number of days the fourth of the six test animals died as the average survival days, dividing this by the average survival days similarly determined from the control animals, and multiplying the value by 100. In addition, exact values calculated using a computer are listed in Examples (Table 2). Although 30 mice were used as a control group, the average value for 6 mice is shown in the table.

[Table] Example 9 A specified amount of N-(5-bromofurylmethylidene)γ-aminopropylpolysilsesquioxane obtained in Example 1 was mixed with surfactant Tween 80 to which a small amount of dimethyl sulfoxide was added. A sample solution was prepared by suspending the sample in a physiological saline solution (0.85 g) containing the following. This sample solution was injected intraperitoneally for 5 consecutive days into 6 Sprague-Dawley rats (female) having 1 x 10 ⁵ Walker Carcinosarcoma 256 cancer cells in their peritoneal cavities for 1 month. The life-prolonging effect was investigated over time. The results are shown in Table 3.

[Table] Example 10 Using the polysilsesquioxanes represented by the following general formulas obtained in Examples 2 to 6, an anticancer activity test against Ehrlichi's ascites carcinoma in mice was conducted in the same manner as in Example 8. . The results are listed in Table 4. O ₁ . ₅ SiCH ₂ CH ₂ CH ₂ N=CH−Ar

【table】

【table】

[Table] Example 11 A polysilsesquioxane represented by the following general formula was synthesized in the same manner as in Example 1, and an anticancer activity test against Ehrlichi's ascites carcinoma in mice was conducted in the same manner as in Example 8. The results are listed in Table 5. O ₁ . ₅ SiCH ₂ CH ₂ CH ₂ N=CH−Ar

【table】

【table】

【table】

【table】 [Brief explanation of drawings]

Figures 1 to 5 of the accompanying drawings are charts showing infrared absorption spectra of polysilsesquioxanes obtained in Examples 1 to 5, respectively.

Claims (1)

[Claims] 1 General formula, [Wherein, Ar is represented by [Formula] or [Formula], and R ₁ and R ₂ are each a hydrogen atom; an alkyl group; a halogen atom; a phenyl group; an alkoxy group; an alkylcarbonyl group; an alkoxycarbonyl group; a carbamide group; A carboxyl group or a salt thereof; a sulfonic acid group or a salt thereof; a nitro group; a cyano group or a group represented by the formula, which is bonded to the 2nd and 3rd carbon atoms of a furan ring or thiophene ring and is closed; ( However, when R ₁ or R ₂ is a hydrogen atom or an alkyl group, other groups, that is, R ₂
or R ₁ is the above-mentioned substituent other than a hydrogen atom and an alkyl group] A polysilsesquioxane having a molecular weight of 700 to 6000 and having a structural unit represented by the following.