JPH06220022A - Pyrimidinone derivative and peptic ulcer medicine containing same as active ingredient - Google Patents

Abstract

PURPOSE:To provide a novel pyrimidinone derivative low in toxicity, having an excellent gastric damage-inhibiting action, useful as a peptic ulcer medicine, and capable of being easily produced. CONSTITUTION:A pyrimidinone derivative of formula I (R1 is amino, nitroamino, cycloalkyleneamine, phenylalkylamine which may be substituted with an alkoxy group, phenylalkylpiperazinyl which may be substituted with an alkoxy group; R2 is phenylalkyl which may be substituted with an alkoxy group, lower alkyl; R3 is lower alkyl, excluding the case where R2, R3 are both methyl and R1 is amino or nitroamino or its salt, e.g. 5,6-dimethyl-2-pyrrolidinyl-4(1H)- pyrimidinone. The compound of formula I is obtained e.g. by reacting a 2- substituted alkylacyl acetate ester of formula II with a C-substituted amidine of formula III.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a pyrimidinone derivative or a salt thereof and an anti-peptic ulcer agent containing them as an active ingredient.

[0002]

2. Description of the Related Art A wide variety of compounds have been known as anti-peptic ulcer agents, and they are roughly classified into defense factor-enhancing drugs and attack factor-suppressing drugs. Many of these have complicated chemical structures and are difficult to manufacture, and there are still problems to be solved in terms of toxicity and side effects. Conventionally, it is known that certain compounds of the pyrimidinone derivative structurally related to the compound of the present invention have an enzyme inhibitory action, an antiviral action and a bactericidal action (for plants) (Journal of Medicin).
al Chemistry Vol. 19, pp. 71-78, 19
1976; Biochemistry, Volume 11, 4723.
-4731, 1972; Chemical and.
Pharmaceutical Bulletin,
Vol. 18, pp. 261-268, 1970; Japanese Patent Publication No. 44-
32600). However, it is completely unknown that these compounds have an anti-peptic ulcer effect.

[0003]

SUMMARY OF THE INVENTION The present invention provides a novel pyrimidinone derivative which is easy to produce and solves the above-mentioned problems of the prior art, and its effect on peptic ulcer has hitherto been achieved. The present invention provides an anti-peptic ulcer agent containing a pyrimidinone derivative which has not been known as an active ingredient.

[0004]

[Means for Solving the Problems] In order to solve the above-mentioned problems of the prior art, the present inventors have synthesized various compounds including a pyrimidinone derivative and tested their anti-peptic ulcer action. Formula (I)

[0005]

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(Wherein R ₁ is an amino group, a nitroamino group, a cycloalkyleneamino group, a phenylalkylamino group which may be substituted with an alkoxy group, a phenylalkylpiperazinyl group which may be substituted with an alkoxy group, and A lower alkylthio group, R ₂ is a phenylalkyl group or a lower alkyl group which may be substituted with an alkoxy group, and R ₃ is a lower alkyl group) or a pyrimidinone derivative thereof The fact that salt has an anti-peptic ulcer effect was found and the present invention was completed.

The compound of the above formula (I) provided in the present invention is explained below. In the above formula (I), R ₁ is an amino group, a nitroamino group, a cycloalkyleneamino group, a phenylalkylamino group which may be substituted with an alkoxy group, and a phenylalkylpiperazinyl group which may be substituted with an alkoxy group. Is selected from the group consisting of. Here, the cycloalkyleneamino group means an azetidino group, a pyrrolidino group, a piperidino group,
A C ₂ C ₆ cyclic alkyleneimino group containing one nitrogen atom such as an azepano group, and a phenylalkylamino group which may be substituted with an alkoxy group is a benzylamino group, a phenethylamino group, a phenylpropylamino group, etc. Is an amino group in which the C ₁ -C ₃ alkylene is substituted on the phenyl group. In this case, the phenyl group may be substituted with about 1-3 alkoxy groups, and the alkoxy group is a methoxy group, an ethoxy group, a propyloxy group, or the like. The phenylalkylpiperazinyl group which may be substituted with an alkoxy group is a C ₁ -C ₃ alkylene group such as an N-benzylpiperazinyl group, an N-phenethylpiperazinyl group or an N-phenylpropylpiperazinyl group. Is a piperazinyl group substituted with a phenylalkyl group having, and in this case, the phenyl group may be substituted with about 1-3 alkoxy groups, and the alkoxy group is a methoxy group, an ethoxy group or a propyloxy group. is there. Further, the R ₁ lower alkylthio group is a thio group substituted with a C ₁ -C ₄ alkyl group such as a methylthio group, an ethylthio group, a propylthio group and a butylthio group.

In the above formula (I), the phenylalkyl group which may be substituted with an alkoxy group for R ₂ is a phenyl group such as benzyl group, phenethyl group or phenylpropyl group, which is substituted with C ₁ -C ₃ alkylene. In this case, the phenyl group may be substituted with about 1 to 3 alkoxy groups, and the alkoxy group is a methoxy group, an ethoxy group, a propyloxy group or the like. Further, in the above formula (I), the lower alkyl group for R ₂ is a C ₁ -C ₄ alkyl group such as a methyl group, an ethyl group, a propyl group or a butyl group.

In the above formula (I), the lower alkyl group for R ₃ is a C ₁ -C ₄ alkyl group such as methyl group, ethyl group, propyl group and butyl group. Therefore, specific compounds of the formula (I) are exemplified below. 5,6-Dimethyl-2-pyrrolidinyl-4 (1H) -pyrimidinone 5,6-dimethyl-2-benzylamino-4 (1H)-
Pyrimidinone 5,6-dimethyl-2- (3,4,5-trimethoxybenzylpiperazinyl) -4 (1H) -pyrimidinone 5-benzyl-6-methyl-2-amino-4 (1H)-
Pyrimidinone 5-benzyl-6-methyl-2-nitroamino-4 (1
H) -Pyrimidinone 5-benzyl-6-methyl-2-pyrrolidinyl-4 (1
H) -Pyrimidinone 5-benzyl-6-methyl-2-piperidino-4 (1
H) -Pyrimidinone 5- (3,4,5-trimethoxybenzyl) -6-methyl-2-amino-4 (1H) -pyrimidinone

As a typical method for producing the compound of the present invention,
It is as follows. The compound (I) of the present invention is, for example,
It can be produced by reacting a 2-substituted alkylacyl ethyl acetate represented by the general formula (II) with a C-substituted amidine represented by the general formula (III).

[0011]

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(In the formula, R ₁ represents an amino group or a nitroamino group, R ₂ represents a phenylalkyl group or a lower alkyl group which may be substituted with an alkoxy group, and R ₃ represents a lower alkyl group). This reaction can be carried out with or without a solvent. When a solvent is used, an organic solvent inert to the reaction, such as methanol, ethanol, propanol, benzene, toluene,
Xylene, dimethylformamide, dimethylsulfoxide, chloroform, tetrahydrofuran, dioxane and the like can be used. In addition, metallic sodium, metallic potassium and the like can be used as a catalyst, the reaction temperature is usually from room temperature to the boiling point of the solvent, and the reaction can be carried out by heating under reflux. When a solvent is not used, it is advantageous to heat the solid-liquid reaction at a high temperature. It is preferable that the starting compounds (II) and (III) are used in equimolar amounts or one of them is used in a slight excess. The reaction time is appropriately set in consideration of the reaction conditions adopted, but is preferably about 1 to 5 hours.

The compound (I) of the present invention is produced, for example, by reacting a pyrimidinone derivative represented by the general formula (IV) with a substituted amine represented by the general formula (V) or the general formula (VI). be able to

[0014]

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(In the formula, X is a nitroamino group or a methylthio group, n is an integer of 2-6, Y is a phenylalkyl group which may be substituted with an alkoxy group, and R ₁ is a cycloalkyleneamino group or an alkoxy group. A phenylalkylamino group which may be substituted with a group or a phenylalkylpiperazinyl group which may be substituted with an alkoxy group, R ₂ is a phenylalkyl group or a lower alkyl group which may be substituted with an alkoxy group, R ₃ Represents a lower alkyl group).
This reaction can be carried out with or without a solvent. When a solvent is used, an organic solvent inert to the reaction, such as methanol, ethanol, propanol, benzene, toluene, xylene, dimethylformamide, dimethylsulfoxide, chloroform,
Tetrahydrofuran, dioxane and the like can be used. The reaction temperature is usually from room temperature to the boiling point of the solvent,
The reaction can be carried out by heating under reflux. When a solvent is not used, it is advantageous to heat and react at a high temperature. It is preferable to use the starting compounds (IV), (V) and (VI) in equimolar amounts or to use one of them in a slight excess, and the substituted amines can be used in a large excess for the reaction. The reaction time is appropriately set in consideration of the reaction conditions adopted, but is preferably about 1 to 5 hours.

The compound of the present invention is effective against human or mammalian peptic ulcer (in the present invention, ulcers in the upper digestive tract such as gastritis and gastric ulcer and ulcers in the lower digestive tract are included in the disease to be treated). It can be applied orally or parenterally for the purpose of its prevention and treatment. At this time, the compound of the present invention, which is an active ingredient, may be used alone, but for suitable use, a suitable formulation is prepared by adding a pharmaceutically acceptable additive to the compound of the present invention. Is applied. Examples of the preparation obtained by such formulation include an oral preparation, an injection preparation, an oral mucosal preparation, a rectal mucosal preparation, and an external preparation.

In the case of a preparation for internal use, the above-mentioned additives are usually selected from ingredients such as excipients, binders, disintegrants, lubricants, corrigents, coating agents, etc. Include tablets, granules, fine granules, powders, syrups, capsules and the like. In the case of injectable preparations, as the above-mentioned additive, an aqueous injection or a preparation component which can constitute a non-hydrated injection is used. Usually, a dissolving agent or a solubilizing agent, a suspending agent, a pH adjusting agent is used. In addition to pharmaceutical ingredients such as stabilizers and the like, pharmaceutical ingredients that can constitute a powder injection for use by dissolving or suspending at the time of administration are also used. In the case of an oral mucosal administration agent, the same formulation ingredients as in the case of the oral preparation are used as the above-mentioned additives, and specific dosage forms include lozenges, buccal agents, sublingual tablets and the like. On the other hand, in the case of a rectal mucosal administration agent, as the above-mentioned additive, a formulation component that can form a suppository, such as an oily base, a water-soluble base, an emulsifier, and a suspending agent is used. In the case of external preparations, formulation components such as fats, fatty oils, lanolin, petrolatum, waxes, resins, plastics, glycols, higher alcohols, glycerin, water, suspending agents, emulsifiers and adhesives are used. Examples of typical dosage forms include ointments, creams and patches.

The above-mentioned components or additives for formulation are known ones, for example, Japanese Pharmacopoeia and its description,
Remington's Pharmaceuticals
l Science (1980 version, Mack Pub
lighting Co. Appropriate amounts of the components for formulation described in (Issue) can be conveniently used. In order to obtain a desired drug of the compound of the present invention by using the above-mentioned components for formulation, the production method described in the 12th revised pharmacopoeia (JP XII) or the production method to which the appropriate modification is added It can be manufactured.

The dose of the compound of the present invention, when converted to the amount of the compound of the present invention, is usually 20 when used orally.
-1000 mg / day, preferably 50-50
It is about 0 mg / day. When used parenterally, it is usually about 10-500 mg / day, preferably 20-
It is about 300 mg / day. The above-mentioned dose specifically refers to the type, site, symptom, peptic ulcer of humans or mammals,
The optimal dose is determined by taking into consideration progress, age, sex, weight, etc.

The following are examples of the compounds of the present invention, synthetic examples,
Formulation examples and test examples on safety and efficacy were shown.

[0021]

【Example】

Example 1 5,6-Dimethyl-2-pyrrolidinyl-4 (1H) -pyrimidinone Pyrrolidine 16 g (0.255 mol) was added to 5,6-dimethyl-2-nitroamino-4 (1H) -pyrimidinone 2.76 (0). (.015 mol) was added and the mixture was refluxed overnight. After the reaction was completed, the reaction solution was distilled off under reduced pressure, and the residue was recrystallized from methanol to give 2.3 g (7) of colorless prism crystals.
9.3%). mp211-212 ° C

Elemental analysis value (C ₁₀ H ₁₅ N ₃ O): Calculated value C; 62.15, H; 7.82, N; 21.7
5; measured value C; 61.98, H; 7.91, N; 2
1.72. Mass spectrometry: EI-MS m / z 193 (M ⁺ ), CI
-MS m / z 194 (M + 1). IR (KBr cm ^-1 ): 1650. MR (δ ppm): 1.8-2.1 (7H, m),
2.2 (3H, s), 3.4-3.8 (4H, m).

Example 2 5,6-Dimethyl-2-benzylamino-4 (1H)-
Pyrimidinone benzylamine 1.0 g (0.01 mol) and 5,6-dimethyl-2-nitroamino-4 (1H) -pyrimidinone 1.8 g (0.01 mol) were refluxed in toluene overnight. After completion of the reaction, the reaction solution was distilled off under reduced pressure, and the residue was recrystallized from methanol to give colorless prism crystals 1.2.
g (52.3%) was obtained. mp175-177 ° C

Elemental analysis (C ₁₃ H ₁₅ N ₃ O): Calculated value C; 68.37, H; 6.60, N; 18.33; Found value C; 68.37, H; 6.63, N : 18.5
6. Mass spectrometry: EI-MS m / z 229 (M ⁺ ),
CI-MS m / z 230 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 2.2 (3H, s), 2.5
(3H, s), 4.4 (2H, m), 7.4 (5H,
s).

Example 3 2.6 g of 5,6-dimethyl-2- (3,4,5-trimethoxybenzylpiperazinyl) -4 (1H) -pyrimidinone 3,4,5-trimethoxybenzylpiperazine
(0.01 mol) and 1.8 g (0.01 mol) of 5,6-dimethyl-2-nitroamino-4 (1H) -pyrimidinone were refluxed in toluene overnight. After completion of the reaction, the reaction solution was distilled off under reduced pressure, and the residue was recrystallized from methanol to obtain 2.2 g (57.9%) of colorless prism crystals. mp252-254 ° C

Mass spectrometry: EI-MS m / z 388
(M ⁺ ), CI-MS m / z 389 (M + 1) IR (KBr cm- ¹ ): 1650. MR (δ ppm): 1.9 (3H, s), 2.2 (3
H, s), 2.4-2.7 (4H, m), 3.5 (2
H, s), 3.6-3.8 (4H, m), 3.9 (9
H, s), 6.6 (2H, s).

Example 4 5-Benzyl-6-methyl-2-amino-4 (1H)-
To 4.5 g (0.025 mol) of pyrimidinone guanidine carbonate, 5.5 g (0.025 mol) of ethyl 2-benzylacetoacetate was added, and the mixture was heated with stirring at 170 ° C. for 6 hours. After completion of the reaction, 10% hydrochloric acid was added to the reaction solution, impurities were extracted with chloroform, the aqueous solution was made alkaline, and the precipitated crystals were collected by filtration and recrystallized from methanol to give 0.5 g of colorless prism crystals (10 %) Was obtained. mp288-2
90 ° C

Mass spectrometry: EI-MS m / z 215
(M ⁺ ), CI-MS m / z 216 (M + 1). IR (KBr cm ^-1 ): 1650. MR (δ ppm): 2.1 (3H, s), 3.5 (3
H, s), 7.2 (5H, s).

Example 5 5-Benzyl-6-methyl-2-nitroamino-4 (1
H) -pyrimidinone 1.5 g of sodium metal in 70 ml of anhydrous methanol
(0.065 mol) was dissolved, 6.0 g (0.0575 mol) of nitroguanidine was added to this solution, and the mixture was stirred under reflux for 1 hour, and then ethyl 2-benzylacetoacetate 11.0 was added.
g (0.0499 mol) is added and the mixture is refluxed overnight. After completion of the reaction, the reaction solution was distilled off under reduced pressure, 50 ml of water was added, the solution was acidified with concentrated hydrochloric acid under ice cooling, and the precipitated crystals were collected by filtration and recrystallized from methanol to give colorless prism crystals 7. 2 g (55.5%) was obtained. mp188-1
91 ° C

Elemental analysis (C ₁₂ H ₁₂ N ₄ O ₃ ): Calculated value C; 55.38, H; 4.65, N; 21.53
Measured value C; 55.18, H; 4.57, N; 2
1.58. Mass spectrometry: EI-MS m / z 260 (M ⁺ ), CI
-MS m / z 261 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 2.1 (3H, s), 3.5
(2H, s), 7.2 (5H, s).

Example 6 5-Benzyl-6-methyl-2-pyrrolidinyl-4 (1
H) -Pyrimidinone Pyrrolidine (30 ml) was added to 5-benzyl-6-methyl-2-
2.2 g of nitroamino-4 (1H) -pyrimidinone
(0.077 mol) was added and the mixture was refluxed overnight. After the reaction was completed, the reaction solution was distilled off under reduced pressure, and the residue was recrystallized from methanol to give 0.89 g (31.
8%). mp202-203 ° C

Elemental analysis (C ₁₆ H ₁₉ N ₃ O): Calculated value C; 71.35, H; 7.10, N; 15.60;
Found C; 71.65, H; 7.11, N; 15.7.
8. Mass spectrometry: EI-MS m / z 269 (M ⁺ ), CI
-MS m / z 270 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 1.7-2.0 (4H, m),
2.2 (3H, s), 3.3-3.6 (4H, m),
3.8 (2H, s), 7.2 (5H, s).

Example 7 5-Benzyl-6-methyl-2-piperidino-4 (1
H) -Pyrimidinone Piperidine (130 ml) was charged with 5-benzyl-6-methyl-2.
-Nitroamino-4 (1H) -pyrimidinone 3.0
(0.0115 mol) was added and the mixture was refluxed overnight. After the reaction was completed, the reaction solution was distilled off under reduced pressure, and the residue was recrystallized from methanol to give 1.6 g (57.1) of colorless prism crystals.
%) Was obtained. mp169-170 ° C

Elemental analysis (C ₁₇ H ₂₁ N ₃ O): Calculated value C; 72.05, H; 7.47, N; 14.83; Found value C; 72.24, H; 7.48, N 14.9
1. Mass spectrometry: EI-MS m / z 283 (M ⁺ ), CI
-MS m / z 284 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 1.5 (6H, s), 2.1
(3H, s), 3.4-3.8 (6H, m), 7.2
(5H, s).

Example 8 5- (3,4,5-Trimethoxybenzyl) -6-methyl-2-amino-4 (1H) -pyrimidinone 1.5 g of sodium metal in 70 ml of absolute ethanol.
(0.065 mol) was dissolved, and guanidine (6.0 g, 0.0575 mol) was added to the solution, and the mixture was stirred under reflux for 1 hour and then ethyl 2- (3,4,5-trimethoxybenzyl) acetoacetate 11 Add 0.0 g (0.0499 mol) and reflux overnight. After the reaction was completed, the reaction solution was distilled off under reduced pressure, and water 5
0 ml was added and the solution was acidified with concentrated hydrochloric acid under ice cooling, and the precipitated crystals were collected by filtration and recrystallized from methanol to obtain 0.4 g (13.3%) of colorless prism crystals. mp252-254 ° C

Elemental analysis (C ₁₅ H ₁₉ N ₃ O ₄ ): Calculated value C; 59.00, H; 6.27, N; 13.76;
Found C; 58.74, H; 6.15, N; 13.7.
7. Mass spectrometry: EI-MS m / z 305 (M ⁺ ), CI
-MS m / z 306 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 2.0 (3H, s), 3.2-
3.5 (11H, m), 6.4 (2H, s).

[0037]

[Synthesis example]

Synthesis Example 1 5,6-Dimethyl-2-methylthio-4 (1H) -pyrimidinone 14.7 g (0.66 mol) of sodium hydroxide was dissolved in 560 ml of water, and 5,6-dimethyl-2- was added to this solution.
28.0 g (0.18) of thio-4 (1H) -pyrimidinone
Mol) and 26.0 g (0.183 mol) of methyl iodide.
Was added and the mixture was heated at 70 ° C for 2 hours. After completion of the reaction, the reaction solution was acidified with concentrated hydrochloric acid under ice cooling, and the precipitated crystals were collected by filtration and recrystallized from methanol to obtain 20.5 g (66.6%) of colorless prism crystals. mp2
23-225 ° C

Elemental analysis (C ₇ H ₁₀ N ₂ OS): C; 4
9.39, H; 5.92, N; 16.46; measured value.
C; 49.47, H; 5.85, N; 16.34. IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 2.1 (3H, s), 2.5
(3, s).

Synthesis Example 2 5,6-Dimethyl-2-nitroamino-4 (1H) -pyrimidinone 250 ml of absolute ethanol and 5.6 g of sodium metal.
(0.245 mol) was dissolved, 22.5 g (0.216 mol) of nitroguanidine was added to this solution, and the mixture was stirred under reflux for 1 hour, and then 27.1 g of ethyl 2-methylacetoacetate.
(0.188 mol) is added and the mixture is refluxed overnight. After the reaction,
The reaction solution was distilled off under reduced pressure, 150 ml of water was added, the solution was acidified with concentrated hydrochloric acid under ice cooling, and the precipitated crystals were collected by filtration.
Recrystallization from methanol gave 26.2 g (75.9%) of colorless prism crystals. mp 300 ° C

Mass spectrometry: EI-MS m / z 184
(M ⁺ ), CI-MS m / z 185 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 2.1 (3H, s), 2.5
(3H, s).

Synthesis Example 3 5,6-Dimethyl-2-amino-4 (1H) -pyrimidinone guanidine carbonate 20.0 g (0.098 mol) and 2-
Ethyl methylacetoacetate 14.3 g (0.011 mol)
Is stirred at 170 ° C. for 6 hours. After the completion of the reaction, the reaction solution was dissolved in 170 ml of 10% hydrochloric acid, neutralized with aqueous ammonia, and the precipitated crystals were collected by filtration and recrystallized from DMF to give 26.2 g (7) of colorless prism crystals.
5.9%) was obtained. mp> 300 ° C

Elemental analysis (C ₆ H ₉ N ₃ O): Calculated value
C; 51.78, H; 6.25, N; 30.20; measured value C; 51.31, H; 6.44, N; 30.16. Mass spectrometry: EI-MS m / z 139 (M ⁺ ), CI
-MS m / z 140 (M + 1). IR (KBr cm ^-1 ): 1650. NMR (δ ppm): 1.9 (3H, s), 2.1
(3H, s).

[0043]

[Formulation example]

 Formulation Example 1 (Formulation example in one tablet) Compound of Example 1 100 mg Lactose 110 mg Crystalline cellulose 20 mg Dextrin 17 mg Magnesium stearate 3 mg Total amount 250 mg

Based on the above-mentioned disposal, tablets were produced according to the method described in the general rules of the Japanese Pharmacopoeia XII formulation.

Formulation Example 2 (Formulation Example in 1 Ampoule of Injection) Compound of Example 1 30 mg Propylene glycol 2 mg Polysorbate 80 2 mg Water for injection Appropriate amount 10 ml

Based on the above formulation, an injection was prepared according to the method described in the general rules of the Japanese Pharmacopoeia XII preparation.

[0047]

[Test example]

Test Example 1 (Acute toxicity test) The compound of the present invention described in Examples and Synthetic Examples was used as 25-2.
8 g of male ddy strain and 220-250 g of S
The LD ₅₀ value was calculated from the mortality rate 2 weeks after the administration by intraperitoneal administration to male D rats. Results: LD ₅₀ value> 1000 mg / kg

Test Example 2 (Hydrochloric Acid-Aspirin Stomach Damage Suppressing Effect on Rats) As animals, Slc: SD male rats (group 3-5) having a body weight of 220-260 g were used after fasting overnight. Each sample was suspended in a 1% gum arabic solution at a concentration such that the administration volume was 0.5 ml per 100 g of body weight, and hydrochloric acid-
It was orally administered 30 minutes before the administration of aspirin. As a general rule, the dose of the sample should be 100 mg / kg, and 1% for the control group.
The gum arabic solution was administered orally. Stomach injury was induced by orally administering 0.5 ml / 100 g body weight of hydrochloric acid-aspirin (suspended in 0.15 M hydrochloric acid so that aspirin was 150 mg / kg) to rats. One hour after that, the rat was sacrificed, and the damage inhibition rate was calculated from the ratio to the damage index of the control group in which only the gum arabic solution was orally administered, using the total length of gastric damage on the gastric mucosa as the damage index. The results are shown in Table 1.

[0049]

[Table 1]

As can be seen from Table 1, the compounds of the present invention were found to have an excellent inhibitory effect on gastric damage.

[0051]

INDUSTRIAL APPLICABILITY The present invention provides a novel anti-peptic ulcer agent having low toxicity and excellent gastric damage inhibitory action.

(72) Inventor Katsuyuki Uchida 2-7-19 Ichinomiya, Samukawa-cho, Takaza-gun, Kanagawa Prefecture (72) Yasuko Igarashi, 5-1-4 Shinshiro, Nakahara-ku, Kawasaki-shi, Kanagawa Prefecture

Claims (2)

[Claims] (1) Formula (1) (In the formula, R ₁ is a group consisting of an amino group, a nitroamino group, a cycloalkyleneamino group, a phenylalkylamino group which may be substituted with an alkoxy group, and a phenylalkylpiperazinyl group which may be substituted with an alkoxy group. those selected, the R ₂ is a phenyl group or a lower alkyl group optionally substituted by an alkoxy group, R ₃
Represents a lower alkyl group. Provided that R ₂ and R ₃ are both a methyl group and R ₁ is an amino group or a nitroamino group)) or a salt thereof. 2. The formula: (In the formula, R ₁ is an amino group, a nitroamino group, a cycloalkyleneamino group, a phenylalkylamino group optionally substituted with an alkoxy group, a phenylalkylpiperazinyl group optionally substituted with an alkoxy group and a lower alkylthio group. R ₂ is a phenylalkyl group or a lower alkyl group which may be substituted with an alkoxy group, and R ₃ is a lower alkyl group, and a pyrimidinone derivative or a salt thereof is effective. Anti-peptic ulcer agent as an ingredient.