JPS60218375A - Novel oxime compound and phrmaceutical composition containing same - Google Patents

Abstract

NEW MATERIAL:An oxime compound of formula I (Het is aromatic heterocyclic group containing one or more N atoms as hetero atoms; X is S or formula II; R is H, lower alkyl or aralkyl; n is 1 or 2). EXAMPLE:(2-Benzoxazolylthio)acetaldehyde oxime. USE:Useful as a remedy for various diseases such as gastric ulcer, duodenal ulcer, gastritis, hyperacidity, etc. having antiulcer activity against intestinal ulcers with low toxidity, and orally and parenterally administrable preferably in 0.5- 50mg dose per kg body weight. 10-1,000mg active constituent is preferably contained in the administration unit form. PREPARATION:For example, a compound of formula III (M is alkali metal) is reacted with a compound of formula IV (Y is halogen or tosyloxy) to give the aimed compound of formula V which is the compound of formula I (X is S).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel oxime compounds having anti-ulcer activity against ulcers of the gastrointestinal tract and pharmaceutical compositions for gastric ulcers and duodenal ulcers containing these compounds.

That is, the present invention relates to the formula % (1) [wherein Het represents an aromatic heterocyclic group containing one or more nitrogen atoms as a heteroatom, and X is S
or represents S, R is a hydrogen atom ↓ still represents a lower alkyl group or an aralkyl group;
n is a number of 1 or 2] and anti-ulcer agents for gastrointestinal tract ulcers containing these compounds as active ingredients.

The compound represented by formula (1) above is a novel compound created by the present inventors, and the present inventors have found that the compound represented by formula (1) has anti-ulcer properties against gastric ulcers and duodenal ulcers. The headline is that it has activity. The present invention is based on this knowledge.

The present invention will be explained in detail below.

To explain the compound of the formula (1), the compound of the formula (1)
) Het in ) is, for example, thiazolyl, oxasilyl, imidazolyl, thiadiazolyl, -triazolyl,
Tetrazolyl, pyridinyl, N-oxide pyridinyl,
Pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, benzimidazolyl, naphthoimidazolyl, benzothiazolyl, benzoxacylyl, quinolinyl, inquinolinyl, quinoxalinyl, imidazopyridinyl, oxazolopyridinyl, purinyl, pyrazolopyrimidinyl,
It is a group selected from the group consisting of naphthyridinyl, quinazolinyl, phthalazinyl and pteridinyl groups, and these heterocyclic groups can have a substituent. Examples of the substituent include one or more lower alkyl groups, halogen atoms, lower alkoxy groups, amine groups, hydroxy groups, carbalkoxy groups, phenyl groups, trifluoromethyl groups, etc. .

The bonding site of the group Het bonded to X in the general formula (1) on the heterocycle can be in various positions within the possible range for each heterocycle. For example, in the case of pyridazinyl, 2-pyridinyl, Q I-' I+ , +1.
− I+, * −h+ +a A −, J) I+
;5, = IF can be attached to LunoF at the 5th, 3rd or 4th position.

The N atom present in the group Het in the general formula (1) is
If it can take the form of N-oxide, it may also be in the N-oxide form.

Examples of lower alkyl groups in the group R include methyl group, ethyl group, n-propyl group, 1-propyl group, n-butyl group, n-pentyl group, n-hexyl group, and cyclohexyl group. Examples include benzyl and phenethyl groups.

The method for producing the compound of formula (1) according to the present invention will be briefly described. A compound (la
): net-8-(CH2)n-CH=N-0-R(la)
[wherein Het, R and n have the meanings as defined in formula 11] can be produced, for example, by the following method.

Production method 1: A compound of the formula, Het -8-M (2) [wherein Het is a group defined in formula (1), and M represents an alkali metal atom],
Formula, Y-(CH2)n-CH=N-0-R (31 [wherein, R
and n have the meanings as defined in formula (1), and Y represents a halogen atom or a tosyloxy group]
to produce a compound of formula (11).

Manufacturing method 2: Formula, net-s-(cH2)n-cu=Q(4) [In the formula, H
et and n have the same meanings as defined in formula (1), and -C)i=Q represents -CH=(] or its acetal type group). R(
51 [wherein R has the meaning as defined in formula (1)] or a salt thereof to form a compound of formula (1).

Manufacturing method 3: Formula, net-8-(CH2)n□CH=N-0-M' (
(3) [where Het, n and M are formula (1) or formula (
21K has the meaning as defined in formula (3)], R-Y (7) [wherein R represents a lower alkyl group or an aralkyl group, and Y has the meaning as defined in formula (3)] having the meaning] to produce a compound of formula (1).

Compound (It) in which X in formula (1) is -8-)
:↓ Het-8-(CH2)H-CH=N-0-R' (l
b)↓ [In the formula, Het, R and n have the meanings as defined in formula (1)] means that X in formula (1) is S
It can be produced from K by oxidizing the compound (1&). Examples of the oxidizing agent used for the oxidation include peracids such as m-chloroperbenzoic acid, hydrogen peroxide, and the like.

The compound of formula (2) can be prepared by a conventionally known method, for example, the following (1).
This can be carried out by methods such as 1 to (3).

(1)') An amine compound such as 2,3-diaminopyridine is reacted with carbon disulfide to form 2-mercapitoimidazo(4,5-b]pyridine.

(2) Reacting a halogeno compound such as 2-bromothiazole with thiourea to produce 2-mercazotothiazole.

(3) Hydroxy compounds such as 1-hydroxyinquinoline are reacted with phosphorus pentasulfide to produce 1-mercaptoisoquinoline.

The oxime compound of formula (1) according to the present invention exists in a mixture of two stereoisomers, namely the syn form and the anti form.

Separation of each of these isomers can be carried out by conventional methods, such as column chromatography.

The compound of formula (1) has various pharmacologically useful properties such as suppressing gastric acid secretion and/or cell protection. The above-mentioned cytoprotective action can enhance the inherent anti-ulcer action of the compound.

The excellent activity and low toxicity of these compounds allow them to be used for the treatment and prevention of inflammatory, ulcerative diseases in the human gastrointestinal tract and diseases based on gastric hyperacidity. For example, acute or chronic gastric ulcers, duodenal ulcers, gastritis, gastric hyperacidity, and various other diseases, such as drug-induced gastritis, can be treated with pharmaceutical compositions containing these compounds. .

The above-mentioned compounds according to the present invention are usually provided in the form of a pharmaceutical composition using a pharmaceutically acceptable carrier or diluent, and the pharmaceutical composition may be, for example, a tablet, coated tablet, powdered tablet, etc. agents, hard and soft capsules, powders, granules,
It can be administered orally or parenterally in various dosage forms such as solutions, emulsions or suspensions.

Compounds of formula (1) or their pharmaceutically acceptable acid addition salts are combined with pharmaceutically inert inorganic or organic excipients for the production of tablets, coated tablets, gunpowders, hard capsules and the like. It can be treated with excipients. As such excipients, for example, lactose, corn starch or its derivatives, cellulose or its derivatives, talc, stearic acid or its salts, etc. can be used for tablets, gunpowders and hard capsules.

Excipients suitable for soft capsules include, for example, vegetable oils, waxes, semisolid and liquid polyols, and the like.

Excipients suitable for producing solutions or syrups include, for example, water, polyols, sucrose, invert sugar, glucose, and the like.

Excipients suitable for injection solutions include, for example, water, alcohols, polyols, glycerin, vegetable oils, and the like.

Suitable excipients for herbal medicines include, for example, natural hardened oils and fats, waxes, fats, semi-solid or liquid polyols, and the like.

Furthermore, the pharmaceutical compositions of the present invention may contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavoring agents or salts to alter osmotic pressure, buffering agents, coating agents or antioxidants. It can be made to contain agents, etc. The composition can still be enhanced by including other substances of therapeutic value.

The dosage of the above compound (1) is appropriately selected depending on the usage, patient's age, sex and other conditions, degree of disease, etc.
Usually, the dosage of the above compound is preferably 90.5 to 50 μg per kg of body weight per day. Further, it is preferable that the dosage unit form contains 10 to 1000 μl of the active ingredient.

Next, in order to better understand the present invention, the formula (1
The production examples and pharmacological properties of the compounds of (a) and (b) will be explained with reference to specific data, but the present invention is not limited to these six examples.

Example 1 (2-benzoxazinorthio)acetaldehyde oxime To a mixture of 200 m9 of sodium hydroxide and 4 me acetonitrile, 755 rng of 2-mercaptobenzoxazole and 161 mg of tetra-n-butylammonium bromide were added with stirring, After a few minutes, 468 η of chloroacetaldehyde oxime obtained by reacting 40 dichloroacetaldehyde solution with hydroxylamine hydrochloride was added to the reaction mixture, and the mixture was stirred for 10 hours. After the produced sodium chloride was separated from the furnace, the solvent was evaporated under vacuum, and the resulting residue was purified by chromatography (S102 column; 1,2-' chloroethane:ethyl acetate-10:1). , and then recrystallized from ethyl acetate and a small amount of n-hexane to obtain the title compound 847 my (section 81).

Melting point: 98-101°C0 In place of the raw material 2-mercaptobenzoxazole in Example 1, the raw material mercapto compound shown in the Example section of Table 1 below was used, and in the same manner as in Example 1. Compounds represented by the formulas listed in Table 1 below were produced.

Table 1 Het -8-CH2-CH=N-OH Example 7 (4-methyl-5-trifluoromethyl-1°2.4-
Triazol-3-ylthio)acetaldehyde 0-
Methyl oxime hydroxide) 4-Methyl-5
-trifluoromethyl-4H-1,2,4-triazoline-3(2H)-thio7366m7 and tetra-bromide
After adding 64wry of n-butylammonium and stirring for 15 minutes, chloroacetaldehyde 0-methyloxime 2157' obtained by reacting 40% chloroacetaldehyde solution with 0-methylhydroxylamine hydrochloride was added.
1Lj was added and the mixture was stirred for 5 hours. The organic layer was separated and dried over sodium sulfate, the solvent was evaporated under vacuum and the resulting residue was chromatographed (5i
Purification by n2 column; 1129 chloroethane:ethyl acetate = 10:l) and then recrystallization from n-hexane and a small amount of ethyl acetate yielded the title compound 420.
■(83chi) was obtained. Melting point: 61-63°C0 In place of the raw material 4-methyl-5-trifluoromethyl-4H-1,2,47) riazoline-3(2H)-thione in Example 7 above, each example in Table 2 below was used. By the same method as in Example 7 using the mercapto compound as the raw material shown in the section,
A compound represented by the formula listed in Table 2 below was produced.

Table 2 Het-8-CH2-CH=N -0-CH382-mercazotothiazole 2-thiazolyl 9 4.6-diphenyl-4-oxazo 4,5-diphenyl-2-oxaline-2-thione Ril 10 4. 5-) Phenyl-2-imidazo 4,5-diphenyl-2-imidalteol Lil 11 2-amino-5-mercapto-1,5-amino-
1,3,4-theacya3.4-thianoazole-2-yl12 5-mercapto-1-phenyl-1-phenyl-1,2,3,4-teto1.2,3.4-tetrazole zole -5-yl13 2-mercaptopyridine 2-pyridinyl]4 2-mercapto-3-t?
Ricinol 3-Hydroxy-2-viridine property/instrumental analysis data Melting point 60-64°G Melting point 123-125°C Melting point 128-130°C La Melting point 62-67°C Mass, (''/e); 182+ 151. +136
1124.111.78 oily material R”-'2'
13100.1570.1445.1310.1195
゜1085, 1030 Ma103O/e); 198.167, 152.1
40.138.134゜27 1145, 1095.1035.840.755 Mas
s(m/e); 198.167, 150.136.
124.123°11.1.88.78 ]7 4-mercaptopyrimidine 4-pyrimidinyl-
18- Oily substance 1R":p'; 1565.1375.1o3
゜Mass (m/e); 183. 152.137.
125 Oily substance 工Ru;y/! ,, 1570.154
5.1330.1030a Mass (m/e) i 197.166, 151.1
39.126.122.94 Melting point 96-98°C Melting point 100-103°C Melting point 126-129°C Melting point 223-227°C (decomposition) Melting point 111-113°C Melting point 66-69°C Oily substance 7t; 1.435.1310.109
5.1030Mass(m/e); 211.180
．． 165.153.140.139.107#U point 1
51-154℃ 30 510 rho 2-mercaptoin 5-chloro-2
-pentthiazolizothiazole 32 2-mercapto-4-methylquino 4-methyl-
2-quinolinyl/33 8-mercaptoquinoline hydrochloride 8-quinolinyl 3711-mercaptoinquinoline 1-isoquinolinyl Melting point 202-205°C (decomposition) Oil Engineering RN? , 1465.1430.1035.
1000.755.725 Tan Melting point 45-48°C Melting point 48-50°C Melting point 47-49°C Oil IRNπ'; 1490.1030.985.
815.785σ Oily material RW7'; 1550.1305.1030
．． 985 Melting point 64-67°C Melting point 166-167°C Examples Raw materials Hθt in the formula 37 2-MercaptoimidazoC4,5-2-imidazo[4,5-C)pyridiCcopyridinyl 39 6-hydroxy-2- Mercapto 6-hydroxy-2-purinylpurine 40 6-mercaptopurine 6-purinyl 41 6-
Amino-8-mercaptopurine 6-amino-8-purinyl 44 1-chloro-4-mercaptophtha 4-chloro-1-phthalazinylradine 45 4-hydroxy-2-mercapto 4-hydroxy-2-pteridinipteridine 46 2-Mercapto-4(3H)-4-hydroxy-2-quinazolininazolinone 47 8-Mercaptoimidazo(1,2-8-imidazo[1,2-a)virilia]pyridine Properties Instrument analysis data solid IRK"-"l"; 1615.1430.13
20.12so, 10300 Stomach Mass (m/e); 222,191+ 176.16
4,151 Melting point 123-125°C Melting point 205-210°C (decomposed) Melting point 161-164°C Melting point 217-221°G (decomposed) Melting point 152-156°C Melting point 77-80°C Melting point 113-117°C Melting point 160-163°C Melting point 157-159°G Oily material R"j'g'; 1490.1325.10
30.735 Buki C Mass (m/e) i 235.204.177, 1
64. , 151.132° Example 48 (2-pyrimidinylthio)acetaldehyde 0-benzyloxime To a mixture of 95 μm of sodium hydroxide and 20 μm of acetonitrile, under stirring, 2-mercaptoimidazo 224 m’i
and 64μ of tetra-n-butylammonium bromide, and after 15 minutes, chloroacetaldehyde 0-benzyloxime 39 was obtained by reacting 40 thichloroacetaldehyde solution with 0-benzylhydroxylamine hydrochloride.
6 TngofA was added and the mixture was stirred for 17 hours. The sodium chloride formed was filtered off, the solvent was evaporated under vacuum and the residue was chromatographed (5i
02 column 1l12 ”Chloroethane:ethyl acetate=1
0:1) to give the title compound 454 (88
%) was obtained as an oil.

Engineering Rsuμi 1560.1545.1375.1200
．． 1175°0π 010 Mass (m/e); 2591 168,138.1
251 112191, 77 In place of 2-mercaptomidine as the raw material in Example 48, the following method was carried out in the same manner as in Example 48, using the mercapto compound as the raw material listed in each example in Table 3 below. Compounds of the formula shown in Table 3 were prepared in Examples 49 and 50.

Table 3 Example 9 1275, 1015', 735 mse (m/e); 261.170°140, 11
4.113.91 Example 51 3-(2-Benzimidazolylthio)zolopionaldehyde oxime 3-(2-benzimidazolylthio) obtained by reacting 2-mercazotobenzimidazole with β-chlorozolopionaldehyde diethyl acetal ) 0.6 m of 12-thihydrochloric acid to a mixture of 560 mg of propionaldehyde diethyl acetal and 278 mg of hydroxylamine hydrochloride.
1 was added and left to stand for 16 hours. Ethyl acetate was added to this mixture, washed with water, dried over sodium sulfate, the solvent was evaporated under vacuum and the resulting residue was chromatographed (5i02 column 1112') chloroethane:ethyl acetate-2=1) and then recrystallized from ethanol to give the title compound 369my (84%). Melting point 119-122°C0 Example 52 (4,6-:)methyl-2-pyriminylthio)acetaldehyde O-7enethyloxime (4,6-:)methyl-2-pyrimidinylthio)acetaldehyP oxime 120 ■ Dimethylformamide 5 m/! 27 μl of sodium 60 thihydride were added in small portions while stirring and cooling to 5°C. After the generation of hydrogen had ceased, 113 μm of phenethyl bromide was added dropwise to the reaction mixture, and after the addition was complete, the mixture was stirred at room temperature for 17 hours. Ethyl acetate was added to this mixture, washed with water, dried over sodium sulfate, and the solvent was evaporated under vacuum. The residue obtained was purified by chromatography (S102 column; 1,2-dichloroethane) and the title 37712g (2
0%) as an oil.

■RNa-C, 4: 1580.1530.1335.
1265.1260. '10200η Mass (m/e); 30L 19L 180+
, 166+ 165+ 153°140.105.91 Example 53 (2-Benzothiazolylsulfinyl)acetaldehyde O-methyloxime ↓ (2-benzothiazolylthio)acetaldehyde O-methyloxime 238mf/, potassium carbonate 138■ and dichloromethane 6 ml of the mixture was stirred while cooling to 0°C and then m-chloroperbenzoic acid 17:lI7
was added little by little. After 1 hour, the mixture was washed with water and
The residue obtained after drying over sodium sulfate and evaporation of the solvent in vacuo was purified by chromatography (5in2 column; 1,2-:)chloroethane) and then recrystallized from ethyl acetate to yield the title compound. 202■ (80
%) was obtained. Melting point 80-83°C.

The same method as in Example 53 was carried out using the sulfide compound as a raw material shown in each example section of Table 4 below in place of (2-benzothiazolylthio)acetaldehyde 0-methyloxime as a raw material in Example 53 above. According to Table 4 below,
Compounds shown in the formula were prepared in Examples 54-56.

Table 4 Het-8'-CH2-CH=N-0-R954 (2-benzimidazolylthio) 2-benzimidazolylacetaldehyde 0-methyloxime 55 (2-pyrimidinylthio)aceto 2-pyrimidinylaldehyro-methyloxime 56 (2-pyrimidinylthio)aceto 2-pyrimidinylaldehyde O-benzyloxime R properties and instrumental analysis data, 1 1f oil IRNa-'gt; 1560.1380
, 1060.1020)4aθs(m/e); 199
,150,128,127,120°112.111,
80.79 Benzyl Melting point 55-60°C Pharmacological action 1. Effect on gastric juice secretion in self-ligated rats The pharmacological action of the compound of the present invention was determined by the method proposed by Hsieh et al. (Gastroenterology'l (1945))
26.906). For this test, male Wistar rats weighing around 1,402 kg were used in groups of 4 to 6 rats. After fasting for U hours, the pylorus of the rat was ligated under ether anesthesia, and immediately thereafter, the test compound (100 μ/g) in the form of a 1% gum arabic suspension or 9 I/gum arabic solution alone was administered into the duodenum. did. After 4 hours, the rats were sacrificed and their gastric juices were drained.

After measuring the volume of gastric juice, its pH was measured.

Regarding the amount of gastric juice, the inhibition rate of the test compound was determined by setting the group administered with 1% gum arabic solution as 0. Regarding pH, the actual values for each administration group were directly compared. These results are shown in Table 5 below.

Table 5 1 83 2 86 2.7g 4 88 5 93 6 87 7 83 8 74 13 51 2.70 576 683 777 476 558 695 27 77 2.33 29 61 2.39 3373 3478 693 092 48 85” 166 54 72 2.78 Note: *50■/9 2. Anti-ulcer activity The anti-ulcer activity of the compound (1) according to the present invention was investigated in a Schiei ulcer experiment.

Male Wistar rats weighing 200 to 230 tons were fasted for 48 hours with 6 rats per group, and under ether anesthesia, Hsieh et al.
The pyloric region was ligated according to the method of (1945). After 18 hours, the rats were sacrificed, and the excised stomachs were immersed in 5-thiformin solution for 5 minutes and then incised along the curvature of the dog. Stretch out your helmet,
The degree of ulceration that occurred in the forestomach was visually observed, and the ulcer coefficient was calculated using the following 5-point method according to the method of Adami et al. (1964) and averaged. compared with the group administered only with Immediately after ligation, the test compound was administered into the duodenum in the form of a 1% gum arabic suspension at a dose of 100 μ/kg.

Ulcer index 0; No change 1; Bleeding or sores 2; 1 to 5 small ulcers (diameter 3 mm or less) 3; 5 or more small ulcers or 1 large ulcer 4; Many large ulcers 5; Perforation test (2-benzimidazolylsulfinyl)acetaldehyde 0-methyloxime was used as the compound.

In this test, (2-be/zoimidazolylsulfinyl)acetaldehyde O-methyloxime showed 53% ulcer inhibition.

3. Cytoprotective effect The cytoprotective effect of the compound (11) according to the present invention was investigated in an ethanol-induced gastric injury experiment.

After fasting for another time, test compound 5 was administered to male Wistar rats weighing 120 to 1,602 kg in the form of a suspension of gum arabic.
9 in 1nf/(dose that does not suppress gastric acid secretion) still 5
Gum thiarabia solution alone (control group) was orally administered. 30
Minutes later, the rats were challenged orally with 1 #1 g of 99.5% ethanol.

After 1 hour, the rats were sacrificed, the stomachs were removed, and saline solution was added for 10 min.
mg was injected intragastrically. After being immersed in a 5-thiformin solution for 5 minutes, an incision was made along the curvature of the gland, and the length of the damage occurring in the blue part of the gland was measured, and the sum of the lengths was taken as the damage factor. The inhibition rate of the test compound on ethanol-induced gastric damage was determined by comparing the test compound administration group and the control group.

(2-benzimidazolylthio)acetaldehyde oxime and (2-pyrimidinylsulfinyl)acetaldehyde 0-benzyloxime were used as test compounds.

In this test, (2-benzimidazolylthio)acetaldehyde oxime showed 38% inhibition of gastric injury and (2-pyrimidinylsulfinyl)acetaldehyde 0-benzyloxime showed 32% inhibition of gastric injury.

4. Toxicity When a toxicity test was conducted using (2-benzimidazolylthio)acetaldehyde oxime, dd
No deaths were observed during the 72-hour observation period even when up to 20 (10 μg/kg (in the form of a 5% gum arabic suspension)) was orally administered to N-strain male mice.

Formulation Example Example A Tablet 2 Corn starch 10.0 12.03 Magnesium stearate -1,01,,04 Crystalline cellulose 30.0 30.05 Hydroxyzorobyl cellulose 2.0 3.06 Lactose 82.0 84.0 150 180 Thoroughly mix ingredients 1.2.4 and 6 in a suitable mixer. A 5-inch aqueous solution of component 5 is added to this mixture, kneaded, granulated, and dried. The dry granules are sized, Component 3 is added, and the mixture is compressed to form 150-inch and 180-inch tablets.

Patent applicant Ota Pharmaceutical Co., Ltd. Continued from page 1■ Int, C1,' Identification code Internal reference number @ Inventor Yasuo Naito 0 Inventor Takashi Kuriyama @ Inventor Yoshi1) Seibu @ Inventor Eiichi Matsuno Jl Old City Kitazono-cho 3-3 Wani Mansion Nakamura 4E 1-1-18 Sumida, Sumida-ku, Tokyo 8 Hata, Nakamachi, Kodaira City M-5, Oyama-cho, Itabashi-ku, Tokyo

Claims (1)

[Claims] 1) Formula: % Formula % [In the formula, Het represents an aromatic heterocyclic group containing one or more nitrogen atoms as a heteroatom, and X is s'
or represents S, R represents water ↓ elementary atom, lower alkyl group or aralkyl group,
n represents a number of ■ or 2]. 2) The above Het is thiazolyl, oxasilyl, imidazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridinyl, N-oxide pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, penzimitazoryl, naphthiimidazolyl, benzothiazolyl,
The claims are groups selected from the group consisting of benzoxasilyl, quinolinyl, isoquinolinyl, quinoxalinyl, imidazopyridinyl, oxazolopyridinyl, purinyl, pyrazolopyrimidinyl, naphthyridinyl, quinazolinyl, phthalazinyl and pteridinyl. A compound according to item 1. 3) Formula (1): %Formula%(11 [In the formula, I(et represents an aromatic heterocyclic group containing one or more nitrogen atoms as a heteroatom, and X is S
or S, R represents a water ↓ elementary atom, a lower alkyl group or an aralkyl group,
A pharmaceutical composition for gastric ulcers and duodenal ulcers, characterized in that it contains an oxime compound represented by the following formula [n represents a number of 1 or 2] as an active ingredient. 4) The above net is thiazolyl, oxasilyl, imidazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridinyl, N7i'/dopyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, benzimidazolyl, naphthiimidazolyl, benzothiazolyl, benzoxasilyl, quinolinyl, inquinolinyl,
Claims No. 1 containing as an active ingredient an oxime compound selected from the group consisting of quinoxalinyl, imidazopyridinyl, oxazolopyridinyl, purinyl, pyrazolopyrimidinyl, naphthyridinyl, quinazolinyl, phthalazinyl and pteridinyl. Pharmaceutical composition according to item 3.