JPH01268670A - 2-nitrobenzoylurea compound, production thereof and anti-cancer drug containing said compound - Google Patents

Abstract

NEW MATERIAL:A 2-nitrobenzoylurea compound shown by formula I {X is group shown by formula II [Y is halogen, nitro, alkyl, etc.; n is 0-4; Z<1> is alkoxy which may be replaced with halogen, group shown by formula III (R<1> is halogen, nitro, etc.; m is 0-4), group shown by formula VI (l is 0-5), formula V (R<2> is halogen, etc.; k is 0-10), group shown by formula VI (j is 0-2), etc.] or group shown by formula VII (Z<2> is alkylene)} or a salt thereof. EXAMPLE:N-(2,2-Difluorobenzo-1,3-dioxolan-5-yl)-N'-(2-nitrobenzoyl)urea. USE:Useful as an anti-cancer drug. PREPARATION:A compound shown by formula VIII (A is isocyanato or amino) is reacted with a compound shown by the formula B-X (B is amino) to give a compound shown by formula I.

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention provides novel 2-nitrobenzoyl urea compounds,
The present invention relates to methods for producing them, anticancer agents containing them, and intermediates thereof.

(Prior Art) Benzoylurea compounds have been described in numerous publications and are well known. For example, JP-A-59-7184, JP-A-59-148763, JP-A-59-176241, JP-A-5
Each publication such as No. 9-176243 discloses a certain benzoyl urea compound. However, the compounds described in these publications have different chemical structures from the 2-nitrobenzoylurea compounds of the present invention in that the phenyl group constituting the benzoyl urea moiety has a different substituent.

(Disclosure of the Invention) The present inventors conducted various studies on benzoyl urea compounds, and found that the phenyl group constituting the benzoyl urea has a nitro group at the ○-position, and the nitrogen atom at the 3-position of the urea moiety. We have discovered that novel compounds with specific substituents exhibit high anticancer activity.

The present invention is based on the general formula (I): a nitro group, an optionally substituted alkyl group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, where n is an integer of O to 4; , Zl is an alkyl group which may be substituted with a halogen atom, a nitro group, or an alkyl group which may be substituted, m is an integer of 0 to 4), l is an integer of O to 5) , is an alkyl group that may be substituted, k is 0 to 10 as described above, j is an integer of O to 2), is an alkyl group or an alkoxy group, and i is an integer atom of 1 to 3, an optionally substituted alkyl group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, h is an integer of 0 to 3), an optional alkylene group)] The present invention relates to a 2-nitrobenzoyl urea compound or a salt thereof.

In the general formula (1), Y, Z', R' to R4
The alkyl group contained in Z2 also includes an optionally substituted alkyl group, an alkoxy group, an optionally substituted alkoxy group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, and an optionally substituted alkyl group. The alkyl moiety constituting the alkylene group which may be substituted with a halogen atom has 1 to 6 carbon atoms, for example,
Examples include methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, etc., and they also include structural isomers of linear or branched aliphatic chains.

Substituents for the optionally substituted alkyl group, optionally substituted alkoxy group, and optionally substituted alkylthio group included in Y, R', R'', and R4 include halogen atoms, etc. There may be one to two or more, and they may be of the same type or different types.

Examples of the halogen atom contained in the compound of general formula (I) include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

In the compound of the general formula (1), since the nitrogen atom in the -NH portion exhibits acidity, a salt can be formed between the compound and an alkaline substance, such as an alkali metal.

Among the compounds of general formula (1), the following are desirable as active ingredients of anticancer agents.

(1) In the benzene ring, Y is at the m-position relative to the bonding position with the nitrogen atom and Zl is at the p-position, or Y
is present at the p-position and Zl is present at the m-position.

(2) Y is a methyl group or a halogen atom which may be substituted with a fluorine atom.

(3) Z'' is alkylene having 1 to 2 carbon atoms which may be substituted with a fluorine atom.

The compound of general formula (I) can be produced, for example, by the following production method.

(X is as described above, A and B are an isocyanate group or an amino group, and when A and B are different from each other, B is an amino group).

The reaction is usually carried out in the presence of a solvent at a temperature of 0°C to reflux, and the reaction time is usually 0.1 to 70 hours.

Examples of solvents include aromatic compounds such as benzene, toluene, xylene, chlorobenzene, and pyridine, aprotic polar solvents such as dimethylacetamide, dimethylformamide, dimethylsulfoxide, and hexamethylphosphoric triamide, diethyl ether, and 1,4-dioxane. ,
Ethers such as tetrahydrofuran, chloroform,
Examples include halogenated hydrocarbons such as methylene chloride and dichloroethane, aliphatic hydrocarbons such as octane and hexane, ketones such as acetone and methyl ethyl ketone, and esters such as ethyl acetate.

The compound represented by the general formula (If) can be produced, for example, by the following method.

(1) Method for producing a compound of general formula (II) in which B is an amino group: In some cases (I[r-3) (III-4) (I[[-5) (the above (a) to (force)) Included in the case, Y-, n, R
'% jsmSR', isR', hSIlSR2, k
and Z2 are as described above, Hal is a halogen atom, and M is a hydrogen atom, potassium or sodium. ) In the reactions (a), (1) and (e) above, when M is a hydrogen atom, the presence of an alkaline substance is required.

Examples of the alkaline substance used in the reaction include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, silver carbonate, sodium hydride, n-butyllithium, potassium tert-butoxide, and the like.
Examples of solvents include aprotic polar solvents such as dimethyl sulfoxide, dimethylformamide, hexamethylphosphoramide, and sulfolane, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, and halogenated hydrocarbons such as methylene chloride and chloroform. Can be mentioned. In particular, in reaction (1), ZS is
Although the above-mentioned ones may be used, tert-butanol is also preferable.

(2) Method for producing a compound of general formula (II) in which B is an isocyanate group: The above general formula (Ill-1), (III-2), (II[
-3), (DI-4) and (I[r-5) at 50 to 150°C in the presence of a solvent.
It can be easily produced by reacting with phosgene for ~24 hours to convert the amino group into an isocyanate group.

Examples of the solvent used in this reaction include those used in the production method (1) above, but dimethyl sulfoxide is undesirable because it reacts with phosgene.

Among the compounds represented by the general formula (n), the compound represented by the following general formula 2B-J(V) is particularly novel.

General formula B-J ... (V) (wherein B is as described above, J is as described above, j, m, i and h are as described above)) or h is as described above) B is an amino group].

Next, representative examples of the compounds represented by the general formula (V) are shown in Table 1.

Table 1 B-J...(V) Table 1 (Continued) Next, synthesis examples of the compounds represented by the general formulas (I) and (V) of the present invention will be described.

Synthesis Example 1 Synthesis of N-(2,2-difluorobenzo-1,3-dioxolan-5-yl)-N'-(2-nitrobenzoyl)urea (compound N113) 4-nitro-2,2-difluorobenzo -2.0 g of 1,3-dioxolane, 0.3 g of 5% palladium-carbon and 25IIIl of methanol
The mixture was reacted for 4 hours at room temperature under a hydrogen atmosphere at normal pressure. After the reaction, methanol was distilled off under reduced pressure, and 2-
Nitropenzoyl isocyaner) 2.4 g and 1.4
-Dioxane 20++j! Add a solution of 1.5 at room temperature.
The reaction was allowed to take place under stirring for an hour. After that, the reaction solution was filtered to remove palladium-carbon, and dioxane was distilled off under reduced pressure.
Purified by silica gel column chromatography,
1.65 g of the target product having a melting point of 189-194°C was obtained.

Synthesis Example 2 Synthesis of N-[3-chloro-4-(5-methyl-2-pyrimidinyloxy)phenyl)-N'-(2-nitrobenzoyl)urea (compound Nll0) (1) 2-chloro-
1.63 g of 5-methylpyrimidine, 1.82 g of 4-amino-2-chlorophenol.

3.50 g potassium carbonate and 22 g dimethyl sulfoxide
0 mJ of the mixture was reacted under nitrogen atmosphere at 130° C. for 3.5 hours with stirring. After the reaction, the reactants are poured into water,
Extracted with ethyl acetate. After washing the extracted layer with saturated saline,
Dry over Glauber's salt and purify by silica gel chromatography to give 3-chloro-4-(
2.28 g of 5-methyl-2-pyrimidinyloxy)aniline (intermediate compound Hikari 5) was obtained.

(2) the intermediate compound 52 obtained in the reaction step (1);
28 g, 2-nitrobenzoyl isocyanate 2,7
A mixed solution of 0 g and 30 mf of 1.4-dioxane was stirred and reacted at room temperature for 2 hours. After the reaction, 1,4-dioxane was distilled off under reduced pressure, 5 ml of methanol was added, and the mixture was filtered. The obtained crystals were dissolved in dimethyl sulfoxide 30-1, poured into water 200+sjj, and the precipitated solid was filtered to obtain 3.16 g of the target product with a melting point of 216-218°C.

Synthesis Example 3 N-(4-[N-(5-bromo-2-pyrimidinyl)sulfamoyl-3-methylphenyl]-N'-(2-
Synthesis of nitrobenzoyl)urea (compound N113) (1) 33.33 g of 2-methyl-4-nitrobenzenesulfonamide, 35 g of 5-bromo-2-chloropyrimidine
．． A mixture of 70 g of potassium carbonate, 42.60 g of potassium carbonate, and 600 m of dimethyl sulfoxide was reacted at 100° C. for 1.5 hours with stirring. After the reaction, the reactants are poured into water,
Extracted with ethyl acetate. Wash the extracted layer with saturated saline,
After drying with Glauber's salt and distilling off ethyl acetate under reduced pressure, it was purified by silica gel column chromatography to obtain white crystals of N-(
7.5 g of 5-bromo-2-pyrimidinyl)-2-methyl-4-nitrosulfonamide was obtained.

(2) 6.0 g of the sulfonamide obtained in the reaction step (1) was dissolved in 80+++j2 of glacial acetic acid, and io.

6.3 g of reduced iron was gradually added and reacted at °C. Thereafter, the temperature of the reaction mixture was returned to room temperature, poured into water, and extracted with methylene chloride. The extracted layer was washed with water, dried with Glauber's salt,
After distilling off methylene chloride, it was purified by silica gel column chromatography to obtain white crystals of 4-amino-N-(5-
2.6 g of bromo-2-pyrimidinyl)-2-methylsulfonamide (intermediate compound number 8) was obtained.

(3) Intermediate compound light 8 obtained in the reaction step (2)
2.6g, 2-nitrobenzoyl isocyanate 1.8
A mixed solution of g and 30 ml of 1,4-dioxane was reacted at room temperature for 4 hours. After the reaction, the reaction product was poured into water, filtered, and washed with ethyl acetate to obtain 1.12 g of the target product having a melting point of 215-218°C.

Next, representative examples of compounds represented by general formula (1) are shown in Table 2.

Table 2 (Continued) Table 2 (Continued) (Effect) The compound of the general formula (1) can be used in experimental animals such as mice, P-3880 Ikemia, L'-1210 Leukemia, B
-16 melanoma, M-5076 sarcoma (sarc
oma), Colon 38, Colon (C
It is effective against cancers such as L. olon 26 and Lewis Lang carcinoma. Meanwhile, certain in vivo test systems and process charts have been developed by the National Cancer Institute to determine the stability of test compounds as antineoplastic agents. These are rCaner Chemotherap
y Reports+■ Part, Volume 3, N112. (1
972), Deran, Green Belve (
Greenberg), MacDonald
ald), Schun+acher
) and Abbott. These process test tables measure standardized pre-tests that are commonly performed in the field of testing for frequent use of anti-tumor drugs. Of these systems, lymphocytic leukemia P-388 is of particular significance to the present invention. These neoplasms were discovered in mice. In general, the good antitumor activity indicated by the % increase in mean survival time of treated (T) animals relative to control (C) animals in these process test tables is consistent with similar results in human leukemia. Suggests.

(Effects of the Invention) Next, the anticancer activity, dosage, and administration method of the compound of general formula (1) will be described, and these compounds exhibit good anticancer activity.

(1) Anticancer activity test example 1 (intraperitoneal - intraperitoneal) BDF, mice were injected with 1 x 106 P-388 leukemia cells.
Compound Hatsuko 1.3.1 after intraperitoneal implantation at the ratio of mice/mouse
For 0.11 and 14, the reagent was administered intraperitoneally twice on the 1st and 8th day, and for compound magnetism 4 to 9 and 12 on the 1st and 4th day, respectively. did.

The survival rate of mice in the control group administered with physiological saline was increased by 1 (ILS, %).
) 0, the increased life extension rate (ILS, %) of each treatment area was determined, and the results are shown in Table 3.

The test drug was prepared according to Formulation Example 8 described later.

Table 3 (Note) *Increase life span (ILS, %)
5pan) and can be calculated using the following formula.

Increased survival rate (ILS, %) = Test Example 2 (intraperitoneal - oral) BDF, mice injected with 1 x 10'' P-388 leukemia cells
Transplanted intraperitoneally at a ratio of 100 mice/mouse, and on day 1 and 8 after transplantation.
The test drug was orally administered twice on the same day. The life and death of the mice were observed for 30 days, and the number of survival days of the mice in the control group administered with physiological saline was increased, and the survival rate (ILS, %) was set as 0.
The increased life extension rate (ILS) of each treatment area was determined in the same manner as in Test Example 1 above.

%) and the results are shown in Table 4. The test drug was prepared according to Formulation Example 8.

Table 4 The compounds of general formula (1) have high anticancer activity regardless of whether the cancer cell inoculation site and the drug administration site are the same or different. The reason for this is not clear, but
This is presumed to be because the compounds of the present invention are also excellent in drug absorption in the gastrointestinal tract, drug concentration in the blood, drug migration to target sites, etc.

(2) Dosage and method of administration In the case of animals, the method of administration is intraperitoneal injection, intravenous injection, local administration, etc., or oral administration, and in the case of humans, intravascular injection into veins or arteries. , as an injection for local administration, or as an oral administration, a suppository, etc.
The dosage is determined by taking into account the results of animal tests and various circumstances, and the total dosage is administered continuously or intermittently within a range that does not exceed a certain amount. However, the dose may be changed as appropriate depending on the administration method, the condition of the patient or treated animal, such as age, weight, sex, sensitivity, diet, administration time, concomitant drugs, and the degree of the patient or the disease. Of course, the appropriate dose and frequency of administration under certain conditions must be determined by a specialist's appropriate dose determination test based on the above guidelines.

The anticancer agent of the present invention is formulated in the same manner as ordinary pharmaceuticals, for example, from an active ingredient and various pharmacologically acceptable auxiliaries, such as an inert diluent, and these are administered orally or intravenously. It is most appropriate to administer the drug by intravenous injection or by suppository.

Furthermore, the content of the active ingredient in the anticancer agent of the present invention varies depending on the differences in various conditions and cannot be unconditionally defined, and the active ingredient may be contained in the same manner as in the case of ordinary anticancer agents, for example, at least 0.001%. It is possible to contain the above active ingredients.

Since the compound of the general formula (1) has a property of being difficult to dissolve in both water and organic solvents, it is preferably made into an aqueous suspension, for example, and may contain a phospholipid. As a method for producing an aqueous suspension that does not contain phospholipids, for example, the active ingredient compound is pulverized in advance, and then the above-mentioned pulverized active ingredient compound is added to an aqueous solution containing a surfactant and, if necessary, an antifoaming agent. Wet grind the powder to a particle size of 5.
An example of this method is to make the thickness 80% smaller than μm, for example, 2 μm or smaller, and add a thickener if necessary. Examples of surfactants include polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, and Si! Examples of antifoaming agents include dimethylpolysiloxane, methylphenylsiloxane, sorbitan fatty acid ester, and polyoxyethylene polyoxypropylene. Examples of thickeners include ethylene/polyoxypropylene cetyl ether and silicone, and examples of thickeners include guar gum, alginic acid, gum arabic, pectin, starch, xanthan gum, and gelatin. On the other hand, as a method for producing an aqueous suspension containing phospholipids, for example, a phospholipid such as soybean phospholipid or egg yolk phospholipid is used instead of the surfactant in the above method, and α -Methods using antioxidants such as tocopherol can be mentioned.

Furthermore, they can be made into tablets, capsules, enteric-coated formulations, powders, injections, suppositories, etc. by conventional pharmaceutical methods.

Next, specific formulation examples of the anticancer agent of the present invention will be given.

Formulation Example 1 70 μm of amorphous powder of the compound of general formula (I) is thoroughly mixed with 30 μm of lactose, and 100 μg each is filled into capsules to prepare oral capsules.

Formulation Example 2 85 parts by weight of amorphous powder of the compound of general formula (I) was mixed with 1.1 parts by weight of grapes, 10 parts by weight of cornstarch, and 5 parts by weight of corn starch.
% cornstarch paste and 1.5 parts by weight of the paste liquid, granulated by a wet method, and 1 part by weight of magnesium stearate is added thereto and compressed into tablets for oral use.

Formulation Example 3 After dissolving 5 g of the compound of general formula (I) in dimethylacetamide 5IIIN, 25 ml of coconut oil was added. .

Pegnol HC-17 (manufactured by Toho Chemical) 7g and HO-1
Add 6 g of 0M (manufactured by Toho Chemical Co., Ltd.) to prepare an emulsion. The same amount of sterilized distilled water is added to this emulsion and subjected to ultrasonication for 20 to 30 seconds to form an oily suspension.

Formulation Example 4 The compound of general formula (1) was pulverized in advance using a centrifugal pulverizer, and then polyoxyethylene (60) hydrogenated castor oil 5
parts by weight, 0.2 parts by weight of silicone and 0.3 parts by weight of polyoxyethylene polyoxypropylene Brochure polymer are added to 79.5 parts by weight of physiological saline to form an aqueous solution,
Therein, the finely divided compound 10 of the general formula (1) is added.
After adding parts by weight and wet-pulverizing in a sand mill using glass beads (80% having a particle size of 2 μm or less), 5 parts by weight of xanthan gum (2% liquid) was added to prepare an aqueous suspension.

Formulation Example 5 The general formula (I) is added to an aqueous solution in which 1.5 parts by weight of oxyethylated polyallylphenol phosphate and 0.2 parts by weight of silicone are dissolved in 53.3 parts by weight of physiological saline.
After adding 40 parts by weight of the compound and wet grinding with a sand mill using glass beads (90% particle size is 2 μm or less),
Add 5 parts by weight of xanthan gum (2% solution) to prepare an aqueous suspension.

Formulation Example 6 The compound of general formula (I) is pulverized in advance using a centrifugal pulverizer. Egg yolk phospholipid 2! 5 parts by weight of the pulverized compound of general formula (1) was added to an aqueous solution prepared by stirring and dispersing 0.001 part by weight of α-tocopherol and 92.999 parts by weight of physiological saline, and the mixture was milled with a sand mill using glass beads. Wet-grind (80% particle size is 2 μm or less) and form an aqueous suspension.

Formulation Example 7 The compound of general formula (1) was pulverized in advance using a centrifugal pulverizer, and then polyoxyethylene (60) hydrogenated castor oil 5
Parts by weight were added to 60 parts by weight of physiological saline to form an aqueous solution, to which 30 parts by weight of the above-mentioned finely divided compound of general formula (1) was added and wet-pulverized in a sand mill using glass beads (particle size of 2 μm or less was obtained). 80%), then xanthan gum (2
% liquid) to prepare an aqueous suspension.

Formulation Example 8 Add the above to an aqueous solution prepared by dissolving 1.5 parts by weight of oxyethylate sodoboriallyl phosphate, 0.2 parts by weight of silicone, and 0.3 parts by weight of polyoxyethylene/polyoxypropylene block polymer in 81 parts by weight of physiological saline. 10 parts by weight of the compound of general formula (1) was added and wet-pulverized with a sand mill using glass beads (90% of the particles had a particle size of 2 μm or less).
), 7 parts by weight of xanthan gum (2% solution) is added to prepare an aqueous suspension.

Patent applicant: Ishihara Sangyo Co., Ltd.

Claims (4)

[Claims] (1) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) [In the formula, X is ▲There are mathematical formulas, chemical formulas, tables, etc.▼Group (Y
is a halogen atom, a nitro group, an optionally substituted alkyl group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, n is an integer of 0 to 4, and Z^1 is a halogen atom. There are optionally substituted alkoxy groups, ▲numerical formulas, chemical formulas, tables, etc.▼group {R^1 is a halogen atom, a nitro group, or an optionally substituted alkyl group,
m is an integer from 0 to 4), ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ groups (R^1 is as described above, l is an integer from 0 to 5), ▲ Numerical formulas, chemical formulas, tables, etc. There are ▼ groups (R^2 is a halogen atom or an optionally substituted alkyl group, and k is an integer from 0 to 10), ▲numerical formulas, chemical formulas, tables, etc.▼ groups (R^
1 is as described above, and j is an integer from 0 to 2), ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ groups (R^1 and m are as described above), ▲ Numerical formulas, chemical formulas, tables, etc. etc. ▼ group (R
^3 is an alkyl group or alkoxy group, i is an integer from 1 to 3), ▲ Numerical formula, chemical formula, table, etc. ▼ group (R^4 is a halogen atom, an optionally substituted alkyl group, a substituted is an optionally substituted alkoxy group or an optionally substituted alkylthio group, h is an integer from 0 to 3), ▲ mathematical formula, chemical formula, table, etc. ▼ group (R^1 and h are as described above) ) or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ It is a group} or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ It is a group (Z^2 is an alkylene group that may be substituted with a halogen atom)] A 2-nitrobenzoylurea compound represented by: or a salt thereof. (2) General formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, A is an isocyanate group or an amino group) A compound represented by the general formula: B-X [wherein, X is ▲ mathematical formula, There are chemical formulas, tables, etc.▼Group {Y
is a halogen atom, a nitro group, an optionally substituted alkyl group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, n is an integer of 0 to 4, and Z^1 is a halogen atom. There are optionally substituted alkoxy groups, ▲numerical formulas, chemical formulas, tables, etc.▼group {R^1 is a halogen atom, a nitro group, or an optionally substituted alkyl group,
m is an integer from 0 to 4), ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ groups (R^1 is as described above, l is an integer from 0 to 5), ▲ Numerical formulas, chemical formulas, tables, etc. There are ▼ groups (R^2 is a halogen atom or an optionally substituted alkyl group, and k is an integer from 0 to 10), ▲numerical formulas, chemical formulas, tables, etc.▼ groups (R^
1 is as described above, and j is an integer from 0 to 2), ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ groups (R^1 and m are as described above), ▲ Numerical formulas, chemical formulas, tables, etc. etc. ▼ group (R
^3 is an alkyl group or alkoxy group, i is an integer from 1 to 3), ▲ Numerical formula, chemical formula, table, etc. ▼ group (R^4 is a halogen atom, an optionally substituted alkyl group, a substituted an optionally substituted alkoxy group or an optionally substituted alkylthio group, and h is 0
is an integer of ~3}, ▲ There is a mathematical formula, chemical formula, table, etc. ▼ (R^1 and h are as described above) or ▲ There is a mathematical formula, chemical formula, table, etc. ▼ is a group) or ▲ Mathematical formula, There are chemical formulas, tables, etc. ▼ (Z^2 is an alkylene group that may be substituted with a halogen atom), B is an amino group or an isocyanate group, A and B are different from each other, provided that X is ▲ There are mathematical formulas, chemical formulas, tables, etc. In the case of the ▼ group, B is an amino group. General formula (I) characterized by reacting with a compound represented by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) A method for producing a 2-nitrobenzoylurea compound. (3) An anticancer agent containing the compound according to claim 1 as an active ingredient. (4) General formula: B-J...(V) [In the formula, J is a ▲ mathematical formula, chemical formula, table, etc. ▼ group (Y
is a halogen atom, a nitro group, an optionally substituted alkyl group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, g is an integer of 1 to 4, and Z^3 is ▲ formula, There are chemical formulas, tables, etc. ▼ groups (R^1 is a halogen atom, nitro group, or an optionally substituted alkyl group, and j is an integer from 0 to 2), ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ There are groups (R^1 and m are as mentioned above), ▲ mathematical formulas, chemical formulas, tables, etc. ▼ groups (R
^3 is an alkyl group or alkoxy group, i is an integer from 1 to 3), ▲ Numerical formula, chemical formula, table, etc. ▼ group (R^4 is a halogen atom, an optionally substituted alkyl group, a substituted Alkoxy group that may be substituted or alkoxy group that may be substituted ▲ There are mathematical formulas, chemical formulas, tables, etc. R^1 and h are as mentioned above) or ▲ there is a mathematical formula, chemical formula, table, etc. ▼ group) or ▲ there is a mathematical formula, chemical formula, table, etc. ▼ group, and B is an amino group or an isocyanate group Yes, but J is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Groups (Y, g, R^1
and h are as described above), B is an amino group].