JPS63255223A - Antiulcer - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the use of new and known semicarbazone derivatives as anti-ulcer agents.

Certain semicarbazones and thiosemicarbazones have antibacterial activity and are used in chemotherapy [J,M
, Patel, M.P., Dave
, N.A., Langaria, K.

A. Thaker, Journal of
Indian Chemical Society (J, I
ndian Chem, S oc, ) 6↓(8),
718-720 (I984); Cl shear patent application (Ru
ssian Patent Appl 1cat
1on) No. 770.045; P, S, Fernandes, V, V-Na
dkar n Y s Journal of Indian Chemical Society 52 (I1), 1059-
1062 (I975); F, Fuji Saiki, R, Hirao, T
.

Shiota, M, Natio, S, Tsukuma, Pharmaceutical Journal I2, l 493-1500 (I967)
].

Similarly, certain semicarbazones and thiosemicalper I-
Nol + 6 + 1 / Wari Suga Iuram (Kutai Isu "V ^ Sui,
Annual Report of Takeda Research Laboratory (Ann, Rap, Takeda Res, L'
ab,) 2U, 144-168 (I968); D, M,
Wifes, T., Sprunczuk (S u
prunchuk), Medical Chemistry (Med)
, Chem, ) ± 1 (3), 252-254 (I971
)].

Furthermore, it is known from animal and clinical studies in China that the healing rate of patients with gastric and intestinal ulcers treated with flagilidone (A) is significantly higher than that of patients treated with cimetidine. . However, the use of flagilidone for the treatment of ulcers is severely limited due to its toxicity.

General formula (I) below, where X represents O, NH or NCH3, and Y represents 0 or S
and R represents amino, alkoxy with up to 6 carbon atoms, represents benzyloxy, or in the above formula R1 represents hydrogen, halogen, nitro, hydroxyl, amino, up to 4 in the alkyl group represents alkylamino or acetylamino with up to 8 carbon atoms, and R8 represents hydrogen, sulfalkoxy, nitro, halogen, sulfamoyl or 3-methyl-2-butenyloxy with up to 8 carbon atoms; It has been found that the semicarbazone derivatives shown below have good anti-ulcer effects.

Surprisingly, compared to the current state of the art, the formula (I
) semicarbazone derivatives have better anti-ulcer effect and less toxicity.

Semicarbazone derivatives according to the invention are generally defined by formula (I).

In this formula, X preferably represents 0, NH or NCH, Y preferably represents 0 or S, and R preferably represents amino, benzyloxy, or preferably In the formula R1 represents hydrogen, nitro or acetylamino, and R3 represents hydrogen, fluorine, chlorine, bromine, methoxy, butoxy, octoxy, sulfamoyl, nitro or 3-methyl-2-butenyloxy.

Particularly preferred compounds of the general formula are those as shown in the table below: 0 0 NH.

NCHs o −NH%oc mountain 0 0 −
NHC0CsH+y NHO-NH%0CsH+t NCHs O-NH+OCJ+ to o
-NH-CI-NO NHO-NH-CI-NO NCH,O-No()N.

NHS -NH.

Very particular preference is given to the throatol-2-aldehyde N'-(4-methoxyphenyl)semicarbazone of formula (Ia).

The new and known semicarbazones of the general formula (I) are the aldehydes of the general formula (I[), where X has the above meanings, the semicarbazides of the general formula (III), where Y and R have the above meanings, or It can be prepared by reaction with thiocarbazide in an inert solvent, optionally in the presence of a catalyst.

The manufacturing process can be illustrated by the following scheme: Suitable inert solvents are water or common organic solvents that do not change with the reaction conditions. These are preferably alcohols such as methanol, ethanol, furopanol or isopropanol, or ethers such as diethyl ether, butyl methyl ether, dioxane, tetrahydrofuran or glycol dimethyl ether, or carbonized alcohols such as benzene, toluene or xylene. Includes hydrogens, or amides such as dimethylformamide or hexamethylphosphoric triamide, or acetic acid. Furthermore, it is also possible to use mixtures of the abovementioned solvents.

In particular, methanol, ethanol, optionally mixed with water
Particular preference is given to using alcohols such as propatool or isopropatool.

Protic acids are commonly used as catalysts. These are preferably free from hydrochloric acid or sulfuric acid, such as hydrochloric acid or sulfuric acid. ! I acids, or organic carboxylic acids having up to 6 carbon atoms, optionally substituted with fluorine, chlorine and/or bromine, such as, for example, acetic acid, trichloroacetic acid, trifluoroacetic acid or propionic acid, or C,- Included are sulfonic acids having C,-furkyl or aryl residues, such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid or toluenesulfonic acid. Benzenesulfonic acid or toluenesulfonic acid is particularly preferably used.

The water formed during the reaction can optionally be removed during or after the reaction in a mixture with the solvent used, for example by distillation or by addition of water extractants, such as molecular sieves.

The reaction is generally carried out at 0°C to +100°C, preferably +2
It is carried out at temperatures ranging from 0°C to +80°C.

The reaction is carried out at atmospheric pressure, increased pressure or reduced pressure (e.g. 0.5 to 5
This can be done in a bar. Generally carried out under atmospheric pressure.

When carrying out the reaction, starting materials are generally used with a molar ratio of aldehyde to semicarbazide of 0.5:2 to 1:1.5. However, equimolar amounts of reactants are preferably used.

The aldehydes used as raw materials are known [Merck Index I 0
14179; Beilstein's Handbook of Organic Chemistry
'5Handbook of Organjc Che
mistry) 3rd Saturday, 270; next day 2, 24].

Semicarbazide and thiosemicarbazide of the general formula ([1)] used as raw materials are known or can be produced by known methods. Depending on the meaning of the residue R, semicarbazide and thiosemicarbazide can be used, for example, in 7-Houben-Weyl's "Method".
(Organischen Chamie)
"■ Volume, 168: ■ Volume 905, GatLermann, H., W.
ieland) by Waiterde Gruyter GmbH, Berlin, 195
``Die Praxis Des O Organischien Hemicus'' published in 2006.
rgabischen Chemikers) 37th edition,
by the reaction of isocyanates or inthiocyanates with hydrazine, as described on page 122, or by the reaction of H. Billman, E.S.

Organic by C1eland
Synthesis Collection (Org, 5ynth,
It can be produced by reacting hydrazine with carbon disulfide and then by a hydrazine decomposition method, as described in J. Col., Volume 1, 360 (I955).

Among the semicarbazone derivatives of general formula (I) used according to the invention as antiulcer agents, the following compounds shown in the table are new and can be prepared by the above method:
R The compounds of general formula (I) used according to the invention, as already mentioned, exhibit not only low toxicity but also a good anti-ulcer effect and can therefore be used in the treatment of peptic and duodenal ulcers. can.

Anti-ulcer activity was determined in a pathological model of gastric ulcer induced by indomethacin in rats.

The test substance is administered orally to rats in graded doses;
A parallel control group received no protectant.

Indomethacin was administered half an hour after administration of the test substance;
The extent of lesions was quantified either by gastric erosion counts (Nu, Er, ) or by score. Percent ulcer inhibition was determined for each group using the following formula: Nu,Er, -Nu,Er.

(Control) The acute toxicity expressed by LDsa was determined by Litchfield (
L 1tchfield) and Wilcoxon (W i
1 cox.

Measured by method n). Relative toxicity was quantified using the following formula: The test results are summarized in the table below: The new active substance was determined using an inert, non-toxic, pharmaceutically suitable excipient or solvent. It can be converted into conventional pharmaceutical forms such as tablets, coated tablets, pills, granules, aerosols, syrups, emulsions, suspensions, and solutions.

The therapeutically active compound accounts for about 0.5 to 9 of the total mixture.
It must be present at a concentration of 0% by weight, ie, in an amount sufficient to achieve the indicated dosage range.

Preparations are prepared, for example, by extending the active compound with solvents and/or excipients, optionally using emulsifiers or dispersants, and optionally using organic solvents as co-solvents, for example when water is used as diluent. It can be used as

Two examples of auxiliaries that should be mentioned are paraffins (e.g. mineral distillate), vegetable oils (e.g. peanut/sesame oil), alcohols (e.g. ethyl alcohol and glycerol).
Non-toxic organic solvents such as natural rock powders (e.g. kaolin, alumina, talc and chalk), synthetic rock powders (e.g. highly dispersed silica and silicates) and solid excipients such as sugars (e.g. sucrose, lactose and glucose). Excipients, emulsifiers (e.g. polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, alkyl sulfates and aryl sulfonates), dispersants (e.g. sulfite lignin waste, methylcellulose, starch and polyvinylpyrrolidone) and lubricants (e.g. magnesium stearate, talc, stearic acid and sodium lauryl sulfate).

Administration is in the usual manner, preferably orally or parenterally,
It is particularly preferably carried out translingually or intravenously. For oral administration, the tablets may of course contain, in addition to the excipients mentioned above, additives such as sodium citrate, calcium carbonate and dicalcium phosphate, various additives such as starch, preferably potato starch, gelatin, etc. It can be contained together with target substances. Additionally, lubricants such as magnesium stearate, lauryl sulfate and talc can also be used in making tablets. In the case of aqueous suspensions, the active compounds can be mixed, in addition to the auxiliaries mentioned above, with various aroma improvers or colorants.

For parenteral administration, the active compound can be employed as a solution in a suitable liquid vehicle.

Generally, for effective results, for intravenous administration,
Approximately 0.001 to 11 g/kg body weight, preferably about 0.001 g/kg body weight. It is convenient to administer an amount of between 0.1 and 0.5119 kg of body weight, and in the case of oral administration, the dosage is about 0.00 m/kg of body weight. 1 to 20 II g, preferably from 0.1 to 10119, but sometimes deviations from the above amounts may occur, especially as a function of body weight or the nature of the method of administration, and also individual behavior towards the drug or formulation of the drug. It may be necessary to do so because of the nature of the agent and the time or interval at which the administration takes place. Therefore, in some cases it may be sufficient to treat less than the above-mentioned minimum amount, while in other cases the above-mentioned upper limit may have to be exceeded. When administering relatively large amounts, it may be advisable to administer this dosage in several doses over a - day treatment period.

Preparation Example ①, General method for preparing compounds of general formula (I): equivalents of aldehyde (If) and semicarbazide (III) are mixed in a suitable solvent such as water or alcohol at a temperature of 50° C. to +80° C. The reaction is induced with stirring at a temperature in the range of +20 to +50°C, with or without para-toluenesulfonic acid. The reaction time depends on the raw materials used and can be from several minutes to several hours.

The precipitated crystals are separated in a suction furnace and washed with water or an aqueous alcohol solution. The desired product is obtained after recrystallization from a suitable solvent.

Il, General process for the preparation of N'-substituted phenylsemicarbazones: a) Preparation of N'-substituted phenylsemicarbazides 1.5 mol of carbon disulfide and 150 ff (25-28%)
The ammonia mixture is cooled in water and, with vigorous stirring, a solution of 1 mol of the appropriate substitute for aniline in 150 mQ of 95% strength ethanol is added dropwise. When the precipitated crystals are separated in a furnace and washed with ethanol, ammonium phenyldithiocarbamate is obtained in quantitative yield.

1 mole of this salt is dissolved in approximately 250 ml of water.

A solution of 1 molar lead nitrate in 70 cod water is added to this solution with constant stirring. The mixture is then IN
of sulfuric acid by steam distillation into a receiver containing sulfuric acid.

The distillate is extracted three to five times with methylene chloride. The organic phases are combined and dried over anhydrous sulfuric acid. The solvent is removed by evaporation in vacuo and the residue is then distilled under reduced pressure. The yield of phenyl isocyanate substitution is 40-60% of theory. 2 moles of hydrazine hydrate (80 to 85%) and L OOtxQ (I'
) 101 with stirring a mixture of ethanol (95%)
A solution of 1 mol of the phenyl isocyanate substitute in 00R ethanol (95%) is added dropwise at a temperature below 25°C. The reaction mixture is cooled and the resulting crystals are filtered out and washed with cold ethanol. N4-substituted phenyl semicarbazide is obtained with a yield of 90-95%.

b) Method for producing N'-substituted phenylthiosemicarbazone Add an equivalent amount of heterocyclic-2-aldehyde dissolved in ethanol to a heated and stirred solution of N41-substituted phenylthiosemicarbazide dissolved in appropriate amounts of ethanol and water. Add dropwise in the presence of traces of vara-toluenesulfonic acid. The precipitated crystals are cooled in a water bath for several hours, filtered out and washed with ethanol. By recrystallizing from a suitable solvent,
The product is obtained with a yield of about 45%.

IIl, General method for producing N'-R-substituted phenylsemicarbazone a) Process for producing N'-1-substituted phenylsemicarbazone 8
A solution of 1.5 moles of sodium cyanate dissolved in 00m(2) of water was dissolved in glacial acetic acid (I00-500 cod glacial acetic acid/300 to 1.000mQ of water) to which water was added.
The molar solution of the aniline substitute is slowly added with stirring at a temperature above +35° C. When the reaction product begins to precipitate, the remaining solution is added to the reaction mixture. The reaction mixture is left at room temperature for several hours. 1.000 mα of water is added, the mixture is cooled, and the crystals are then filtered out, washed with cold water and dried. The phenylurea substitution product is obtained in a yield of 85-95%. A mixture of 1 mol of the phenylurea substitute and a 25% strength aqueous hydrazine hydrate solution is heated under reflux for 5-7 hours. When the phenylurea in the reaction mixture is consumed (checked by thin layer), the reaction mixture is cooled to 0° C., filtered and the residue is washed alternately with cold water and a suitable solvent. Recrystallization from a suitable solvent gives N4- in 30-60% yield.
A substituted phenyl semicarbazide is obtained.

b) Method for producing N'-substituted phenylsemicarbazone 1 mol of N4-substituted phenylsemicarbazide is dissolved in a hot aqueous ethanol solution. A catalytic amount of bara-toluenesulfonic acid is added to this solution, followed by dropwise addition of a solution of 1 molar aldehyde in ethanol of 5011IQ. Stir the reaction mixture at room temperature1. Body - dream F';It'a-tsl
Wash and dry the AMsj)-p+, 1. When the crystals are purified by recrystallization from a suitable solvent, 85-95%
The N4-substituted phenyl semicarbazone is obtained in a yield of .

■, Production Example Wataru Toho - Ubilol-2-aldehyde N'-(4-methoxyphenyl) semicarbazone υ a) 4-methoxyphenyl acetic acid water soluble i (I50mQ f) Glacial acetic acid/1,000ma
With vigorous stirring, a solution of 1.5 mol of sodium cyanate in 1.000 m of water is rapidly added dropwise to a solution of 1 mol of 4-methoxy-aniline in 1.000 m of water. A white precipitate precipitates out with the evolution of (temperature approximately 45° C.). After several hours at room temperature, the reaction mixture is cooled in a water bath and the residue is washed with water until the washing water is neutral.

Yield: 92.1% of theory Melting point: 159-160°C b) N'-(4-methoxyphenyl)semicarbazide 1
A mixture of 388 m<2 of a 25% strength solution of 61.5 g (0.97 mol) of 4-methoxy-phenylurea and 1.94 mol of hydrazine hydrate is added until the phenylurea is completely consumed (dilute Layer check, silica gel GF, methylene chloride:methanol-10:0.4) Heat under reflux for 7 hours. The reaction mixture is diluted with 200rsQ of water, heated under reflux with 4 g of animal activated charcoal for a few minutes to decolorize, and the solution is filtered. When the furnace liquid is cooled, white crystals precipitate.

After standing overnight in the refrigerator, the crystals are separated from the iron furnace and washed with cold water.

Yield: 110 g The crude product is heated in 500+lIQ of toluene for 10 minutes in a boiling water bath. After cooling in the refrigerator, the crystals are separated in a suction oven and dried.

Yield: 45% of theory Melting point: 197-199°C C) Virol-2-aldehyde N'-(4-methoxyphenyl)semicarbazone○ 809 dissolved in 60% strength ethanol 640rnQ
(0.44 mol) of N'-('4-methoxyphenyl)
A catalytic amount of para-toluenesulfonic acid is added to a hot solution of semicarbazide. Then 95% S ethanol 5
A solution of 449 (0°462 mol) of virol-2-aldehyde in Qmff is added dropwise to this hot solution. The mixture is stirred for an additional hour in a heated water bath. The heated water bath is then removed and the reaction mixture begins to cool. After standing overnight in the refrigerator, the crystals are separated in a suction furnace and washed alternately with cold water and ethanol. The crude product is recrystallized from 95% strength ethanol.

Yield: 92.4% of theory Melting point: 198.5-199.5°C (decomposition) Analysis: C14
H14N 402 Calculated value: C60,45H5,46N 21.69 Analysis value: C60,55H5,54N 21.33UV: max. 310 nm, log=4.47 (in ethanol) I
R: (c+m-') 3400.1670.1660
．． 1650.1607.1532.1512.1256
．． 1240.830.805'H-NMR (90 MHz, d, -in DMSO): δ-
3,80 (s, 3H); 6.14 (+, IH); 6.4
0 (mSI H); 6.96.7.54 (2xd14H
); 7.02 (m, l H); 7.81 (s,
l H); 8.84 (s, L H); l O,00
(s, L H); l l, 06 (s, IH) MS: 258 (M”), 149, 135, 133
(I00%), 108.93.80 Example 2 Virol-2-aldehyde N'-(4-methoxyphenyl)thiosemicarbazone a) Ammonium 4-methoxyphenyldithiocarbamate 2.49 mol of ice-cold disulfide Carbon and ammonia water (
300 ml of 95% strength ethanol into a vigorously stirred mixture of
A solution of 2.0 mol of 4-methoxyaniline in g is added dropwise. The precipitated white crystals are separated in a suction furnace and washed with ethanol.

Yield: Quantitative b) 4-Methoxyphenylthiocyanate 8.76 mol of ammonium dissolved in 20 Q of water. Mix with solution. The resulting mixture is steam distilled. The distillate is extracted five times with methylene chloride. The organic phases are combined and dried over sodium sulfate. The solvent is removed by evaporation in vacuo and the residue is then distilled under reduced pressure.

Yield: 42.8% of theory c) N'-(4-methoxyphenyl)thiosemicarbazide 7.49 mol of hydrazine hydrate (85%) and 723
A solution of mQ ethanol (95%) on ice/chloride.
95% with cooling and continuous stirring in the Jum mixture.
A solution of 3.75 mol of 4-methoxyphenyl isothiocyanate in a concentration of ethanol 277+xff is added dropwise. The temperature is kept below +25°C. Collect the precipitated crystals and wash with cold ethanol.

Yield: 93.1% of theory Melting point: 146-149 °C (decomposition) d) Pyrrole-2-aldehyde N'-(4-methoxyphenyl)thiosemicarbazone 2.500i (50% concentration of 2 Dissolve in ethanol,
While stirring a hot solution of 1,19 moles of N'-(4-methoxyphenyl)thiosemicarbazide with a small amount of vara-toluenesulfonic acid, 1,19 moles of pyrrole-2-aldehyde dissolved in 200 imQ of ethanol were added. Add a solution of The reaction mixture is cooled and the precipitate that separates is filtered off and then washed with diluted ethanol. After recrystallization from absolute ethanol, pyrrole-2-
The aldehyde N'-(4-methoxyphenyl)thiosemicarbazone is obtained.

Melting point: 199-200°C (decomposition) Analysis: C+, H148ao S Calculated value: C56,91H5,14N 20.42 Analysis value: C56,64H4,94N 20.24I R:
(KBr cry-') 3350.1620.1
555.1520.1500.1240.1220,l
040.835.790.755.742'H-NMR (90MHz%d, in -DMSO): δ-
3,76 (s, 3H); 6.61 (m% IH); 6.
48 (m, l H); 7.06 (m, l H); 6.9
6.7°50 (2Xd, J-9, 4H); 7.98 (
sllH); 9.98 (s, L H); 11.52
(s, L H); 11.60 (s, l H) MS: 274 (M”), 183.151.147.1
23 (I00%), 108.93.92.80.79

Claims (1)

[Claims] 1) The following general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) However, X represents O, NH or NCH_3, Y represents O or S, and R represents amino , represents alkoxy with up to 6 carbon atoms, represents benzyloxy, or the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the above formula, R^1 is hydrogen , halogen, nitro, hydroxyl, amino, alkylamino with up to 4 carbon atoms in the alkyl group, or acetylamino, and R^3 is hydrogen, alkoxy with up to 8 carbon atoms, nitro, halogen , sulfamoyl or 3-methyl-
The use of a semicarbazone derivative having 2-butenyloxy, which represents a residue of , for the treatment of diseases, preferably for the control of ulcers. 2) In the general formula (I), X represents O, NH or NCH_3, Y represents O or S, and R represents amino, benzyloxy, or the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the above formula, R^1 represents hydrogen, nitro, or acetylamino, and R^2 represents hydrogen, fluorine, chlorine, bromine, methoxy, butoxy, octoxy, sulfamoyl, nitro, or The use of semicarbazones of the general formula (I) according to claim 1, which represents a residue of 3-methyl-2-butenyloxy, for the treatment of diseases, preferably for the control of ulcers. 3) In the general formula (I), X, Y and R have the following meanings: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Preferably for use in the treatment of ulcers. 4) Use of pyrrole-2-aldehyde N^4-(4-methoxyphenyl) semicarbazone of the following formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ for the treatment of diseases, preferably ulcers. 5) The following general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) However, X represents O, NH or NCH_3, Y represents O or S, and R is amino, up to 6 carbons. Represents alkoxy with an atom, represents benzyloxy, or the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ In the above formula, R^1 is hydrogen, halogen, nitro, hydroxyl , amino, alkylamino with up to 4 carbon atoms in the alkyl group, or acetylamino, and R^2 is hydrogen, alkoxy with up to 8 carbon atoms, nitro, halogen, sulfamoyl or 3-methyl −
A medicament, preferably an anti-ulcer agent, comprising one or more semicarbazone derivatives having 2-butenyloxy, representing the residue of . 6) In the general formula (I), X represents O, NH or NCH_3, Y represents O or S, and R represents amino, benzyloxy, or the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the above formula, R^1 represents hydrogen, nitro, or acetylamino, and R^2 represents hydrogen, fluorine, chlorine, bromine, methoxy, butoxy, octoxy, sulfamoyl, nitro, or 3 - Methyl-2-butenyloxy, which represents the residue of - A medicament, preferably an anti-ulcer agent, comprising one or more semicarbazone derivatives of the general formula (I) according to claim 5. 7) In the general formula (I), X, Y and R have the following meanings: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ One or more semicarbazones of the general formula (I) according to claim 5 Medicaments containing derivatives, preferably anti-ulcer agents. 8) Pyrrole-2-aldehyde N^4-(4-methoxyphenyl) semicarbazone with the following formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ disease, preferably an anti-ulcer agent. 9) A semicarbazone derivative having the following general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In (I), X, Y, and R have the following meanings: ▲There are mathematical formulas, chemical formulas, tables, etc.▼. 10) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) However, X has the above meaning. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (III) A method for producing a semicarbazone derivative of general formula (I), characterized by reacting with semicarbazide or thiosemicarbazide, where Y and R have the above meanings. 11) One or more semicarbazone derivatives according to the general formula (I) in the meaning of one or more of claims 5 to 8 are intimately mixed and formulated with pharmaceutically customary auxiliaries. A method for producing a drug according to any one of claims 5 to 8. 12) A semicarbazone derivative of general formula (I) according to claim 9 for controlling diseases. 13) A semicarbazone derivative of general formula (I) according to claim 9 for producing an anti-ulcer agent. 14) A drug, preferably an antiulcer agent, containing one or more semicarbazone derivatives of general formula (I) according to claim 9. 15) Use of the semicarbazone derivative of general formula (I) according to claim 9 for controlling ulcers. 16) Use of the semicarbazone derivative of general formula (I) according to claim 9 for producing a drug for controlling ulcers. 17) Claim 9, characterized in that the semicarbazone derivatives of general formula (I) according to claim 9 are intimately mixed and formulated with pharmaceutically customary auxiliaries.
A method for producing a drug containing a semicarbazone derivative of general formula (I) as described in 1.