JPS62223164A - Substituted benzophenone oxime ether derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [R<1> and R<2> are H or lower alkoxy; X is group shown by formula II (R<3> is H or lower alkyl), group shown by formula III (R<5> is R<3> and R<4> is lower alkyl), etc.]. EXAMPLE:4,4'-Dimethoxybenzophenone,O-(3-ethoxycarbonyl-2-oxopropyl)oxime. USE:An antiplatelet and an anti-thrombogenic agent having improved inhibitory action on blood platelet aggregation, useful for remedying and preventing cerebrovascular disorder, blood flow disorder, ischemic cardiac diseases, etc. PREPARATION:A benzophenone oxime compound shown by formula IV is condensed with a halide shown by the formula Hal-X (Hal is halogen) in a solvent such as DMF, etc., in the presence of a base at 0-100 deg.C to give a compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to substituted benzophenone oxime ether derivatives and pharmacologically acceptable salts thereof having excellent medicinal effects, methods for producing the same, and pharmaceuticals containing the same.

Prior Art Currently, acute vascular disease9 is one of the diseases that pose a serious health risk to human beings, such as myocardial infarction, stroke, cerebral thrombosis, cerebral infarction, pulmonary embolism, deep vein thrombosis, and peripheral artery occlusion. and so on.

In recent years, it has been used as one of the therapeutic agents for these diseases.

Antiplatelet agents are attracting clinical attention and are becoming widely used, but the history of antiplatelet agents is relatively new, and the development of better drugs is expected in the future.

OBJECTS OF THE INVENTION An object of the present invention is to provide substituted benzophenone oxime ether derivatives and their pharmacologically acceptable salts which have excellent effects as pharmaceuticals, and furthermore, to provide substituted benzophenone oxime ether derivatives and their pharmacologically acceptable salts. The object of the present invention is to provide a method for producing an acceptable salt, and further to provide a medicament containing the substituted benzophenone oxime ether derivative and its pharmacologically acceptable salt as an active ingredient.

Structure and Effects of the Invention The object compound of the present invention is a substituted benzophenone oxime ether derivative represented by the following general formula fIl or a pharmacologically acceptable salt thereof.

Il N-0-X(Il [In the formula, R1 and R2 represent the same or different hydrogen atoms or lower alkoxy groups.

Xl;! , formula CHt C-CH, -C0OR'
(In the formula, R3 means a hydrogen atom or a lower alkyl group) -CH2-C-CH2-COOR
1;I-0R4 (in the formula, R5 means a hydrogen atom or a lower alkyl group;
R' means a lower alkyl group) 2
Formula -CH-(CH,)n-COOR" (in the formula, R6N means a hydrogen atom or a lower alkyl group, and n is 1 to 3
), or a group represented by the formula 2 -(CH
,)m-Y (wherein Y is substituted with a group represented by formula 2-8Ii, a group represented by formula 1-8CN, or a ring having one or more nitrogen or sulfur atoms in the ring) means a monovalent group derived from a good five-shell ring or a six-membered ring; m means an integer of 1 to 2). ] A substituted benzophenone oxime ether derivative represented by

In the above definition, the lower alkyl group found in R', R', R' and R6 refers to a straight or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, n-
Propyl, n-7” thyl, isopropyl, isobutyl,
1-Methylpropyl.

All meanings such as tert-phthyl, n-pentyl, 1-ethylpropyl, isoamyl, n-hexyl, etc.

The lower alkoxy group found in R1 and R2 means all lower alkoxy groups derived from the above-mentioned lower alkyl groups. Of these.

The most preferred lower alkyl groups are methyl and ethyl groups, and the most preferred lower alkoxy groups are methoxy.

Furthermore, in the compound of the present invention (Il, in the definition of Y.

The monovalent group derived from a five-shell ring or a six-shell ring which may be substituted with a ring having one or more nitrogen or sulfur atoms in the ring is specifically, for example, a 1-pyrrolyl group,
1-(1,2,3°4,-tetrazolyl) group, 1
-pyrrolidinyl group.

1.3-dithianyl group, 3-allylmercapto-1,2
, 4-triazolyl group, etc.

Pharmacologically acceptable salts include metal salts such as Na, K, Ca, Mg, etc. when R', R' and 1 or R1'l in the structural formula tIl of the target substance are hydrogen. .

Furthermore, depending on the target substance, it can be easily converted into an acid addition salt by reacting with a pharmacologically acceptable inorganic or organic acid. Such inorganic acids include hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, etc., and organic acids include maleic acid, fumaric acid, succinic acid, etc. 12. malonic acid, citric acid.

Examples include benzoic acid, kojic acid, and methanesulfonic acid.

Production Method There are various possible production methods for the compound of the present invention (Il), but representative methods among these are as follows.

Manufacturing method 1 death I N OX (H (In the formula, R', R2 and X have the above meanings.

Hal means a halogen atom, i.e. 9 formula + II
The benzophenone compound represented by I is reacted with hydroxylamine to obtain a benzophenone oxime represented by formula (2) (Step 1). The reaction temperature is usually about 0 to 200°C, preferably room temperature to 100°C.
C, and the solvent is 9 such as methanol, ethanol,
Proper tools, benzene, toluene, water, etc. can be used.

Step 2 is usually carried out at a reaction temperature of about 0 to 100° C. and a solvent such as dimethylformamide (DMF).

Dimethyl sulfoxide (DMSO), methanol.

Ethanol, propatool, benzene, toluene, etc. can be used. At this time, sodium hydride (Na
Favorable results are obtained by carrying out the reaction in the presence of a base such as 1I), triethylamine, dimethylaniline, potassium hydroxide, sodium methoxy (NaOMe), sodium ethoxy (Na0Et), potassium tert-butoxy.

Production method 2 I R31R' in the definition of N-0-X' M (wherein X' is 9 formula tI)
Unless IR6 is hydrogen, that is, it is a lower alkyl group, the desired substance can be obtained by hydrolyzing the ester with an alkali such as caustic soda in a conventional manner.

Production method 3 General formula (II, X is the formula -CH, -C-CHt-C0OR' N-0-CHt-C-CH, -COOR-N -0-C
H, -C-CH, -GOOR' -0R4 (in the formula, R1, R2, R4, R5 have the above meanings)
That is, compound (1) is subjected to a condensation reaction with an amine represented by "-" by a conventional method to obtain compound (1), which is one of the target substances. This reaction is preferably performed at a temperature of about -20 to 200°C, and methanol, ethanol, propatool, benzene, toluene, water, etc. can be used as a solvent.

Next, two representative compounds of the present invention will be listed.

The purpose of this description is to facilitate understanding of the present invention, and it goes without saying that the scope of the present invention is not limited thereby. Please note that all of the following information is written in free form.

04.4'-dimethoxybenzophenone, 0-(3-methoxycarbonyl-2-oxopropyl)oxime 04.4'-dimethoxybenzophenone, 0-(3-ethoxycarbonyl-2-oxopropyl)oxime 04.4'-dimethoxy Benzophenone, O-(3-methoxycarbonyl-2-methoxyiminopropyl)oxime 04.4'-Dimethoxybenzophenone, O-(3-ethoxycarbonyl-2-methoxyiminopropyl)oxime 04.4'-Dimethoxybenzophenone, o -(3-carboxy-2-methoxyiminopropyl)oxime 04.4'-dimethoxybenzophenone, 〇-(1-cyano-3-methoxycarbonylpropyl)oxime 04.4'-dimethoxybenzophenone, ○-(1-cyano- 3-ethoxycarbonylpropyl)oxime 04.4'-dimethoxybenzophenone, 0-(1-cyano-3-carboxypropyl)oxime 04.4'-dimethoxybenzophenone, 0-(1-cyano-4-methoxycarbonylbutyl)oxime 04.4'-dimethoxybenzophenone, 0-(1-cyano-4-carboxybutyl)oxime 04.4'-dimethoxybenzophenone, 0-(2-[
:1-g3-allylmercapto-1,2゜4-triazolyl)]ethyl)oxime 04.4'-dimethoxybenzophenone, 0-(2-[1-(1,2,3,4-tetrazolyl)]ethyl ) Oxime 04.4'-dimethoxybenzophenone, 〇-(2-(
2-(1,3-dithianyl)]ethyl)oxime 04.4'-dimethoxybenzophenone, O-[2-(
1-pyrrolidinyl)ethyl]oxime 04.4'-dimethoxybenzophenone, ○-(2-thiocyanatoethyl)oxime 04.4'-dimethoxybenzophenone, 0-(2-mercaptoethyl)oxime 04.4'-dimethoxybenzophenone ,0-(2-(
1-hyloryl)ethyl]oxime 04.4'-jethoxybenzophenone, 0-(3-ethoxycarbonyl-2
-Oxopropyl)oxime 04.4'-Jethoxybenzophenone, 0-(3-ethoxycarbonyl-2-methoxyiminopropyl)oxime 04.4'-Jethoxybenzophenone, 0-(3-carboxy-2-methoxyiminopropyl) ) oxime 04.4'-jethoxybenzophenone, 0-(1-cyano-3-ethoxycarbonylpropyl)oxime o4,4'-jethoxybenzophenone, 0-(1-cyano-3-carboxypropyl)oxime 04-methoxy Benzophenone, 0-(3-ethoxycarbonyl-2-oxopropyl)oxime o4-methoxybenzophenone, 0-(3-evil)oxime o4-methoxybenzophenone, 0-(3-carboxy-2-methoxyiminopropyl)oxime 04- Methoxybenzophenone, 0-(1-cyano-3
-ethoxycarbonylpropyl)oxime 04-methoxybenzophenone, 0-(1-cyano-3
-carboxypropyl)oxime The substituted benzophenone oxime ether derivative provided by the present invention has an excellent platelet aggregation inhibiting effect, and is a therapeutic agent based on this effect.

be. Specifically, Tewo (transient ischemic attack).

Cerebral infarction (thrombus, embolism), cerebral vascular disorders such as cerebral arteriosclerosis, postoperative thromboses and embolisms and blood flow disorders associated with vascular surgery and extracorporeal blood circulation, Buerger's disease.

Arteriosclerosis obliterans, peripheral arteriosclerosis, SLE, chronic arterial occlusion diseases such as white wax disease, angina pectoris, myocardial infarction'ty fv
J'/711r! ＞It”% fix skewer?”μ
ffi oil is'izi tff+r is useful for preventing recurrence of these diseases and improving prognosis.

Next, pharmacological experimental examples will be presented to explain in detail the effects of the compounds of the present invention.

Experimental Example: 3.8% sodium citrate solution from human cubital vein.
Blood was collected to contain 10ffi, and the method 1 of Packham et al.: Packham, M. A. et al.
, J. Exp. Med, 126.171-18.
9 (1967)).
...Platelet Rich Plasma
) was prepared. Various concentrations of the compounds of the present invention (compounds A to G) were added to 2 ml of this human PRPO.

25 μt of the solution was added and incubated at 37° C. for 3 minutes to induce platelet aggregation with arachidonic acid, collagen, ADP and PAF. Platelets are manufactured by Cienko,
Or Aggrego, manufactured by Binary Biosciences.
Using etor, the method of Mustard et al.
ard.

J, f? , et al. J. Lab C11
n, Mad, 64.548-559 (1964)
).

The results are shown in Table 1.

2. Platelet aggregation inhibitory effect (ex vivo) Compounds A-G, representative compounds of the present invention, were orally administered to guinea pigs, and 2 hours later, blood was collected from the abdominal aorta under ether anesthesia, and collagen (3 μg/nL) and arachidone were collected. The inhibitory effect of acid (50 μM) on platelet aggregation was investigated. Find the solvent administration rate.

5096 effective doses are shown in Table 2.

Table 2 3. Acute toxicity Representative compounds of the present invention compounds (compounds A-E):
Rat (Weight 300-400 g Wistar male)
When an acute toxicity test was conducted using LD,...
Yes, all of them were 500 mg/μg or more.

When the compound of the present invention is used as an antiplatelet agent or an antithrombotic agent, it can be administered orally or parenterally (intramuscularly, subcutaneously,
Administered intravenously (intravenously, etc.). Dosage varies depending on the disease,
The severity of symptoms varies depending on factors such as age, but is not particularly limited, but for adults it is usually about 0.1 to 300 m9 per day. Preferably 0.1-60 mg.

More preferably 0.3 to 30 mg, still more preferably 0.
It is 6-10+++g.

In order to formulate a compound of the present invention, it is formed into a dosage form such as a tablet, granule, powder, capsule, injection, herbal medicine, etc., by a conventional method in the field of pharmaceutical preparation.

That is, when preparing oral solid preparations, excipients are added to the crude drug, and if necessary, binders and disintegrants are added.

Lubricants 9 After adding coloring agents, flavoring agents, etc., the mixture is prepared into tablets, coated tablets, granules, powders, capsules, etc. by conventional methods.

Add pH adjusters, buffers, stabilizers, preservatives, etc.
Administer as subcutaneous, intramuscular, or intravenous injection using conventional methods.

Example 1 Synthesis of oxime (114,4'-dimethoxybenzophenone oxime) 4.242 g (1 mol) of 4'-dimethoxybenzophenone was suspended in 2.000 mL of ethanol, and 210 y (3 mol) of hydroxylamine hydrochloride was suspended in 2.000 mL of ethanol. , I
Add 300ml (3 mol) of QN-NaOH aqueous solution,
Heat to reflux. After 2 to 3 hours, ethanol is distilled off under reduced pressure, and then brine is added and extracted with chloroform. The chloroform layer is washed with water and dried over magnesium sulfate, and after distilling off the chloroform, the remaining bath is recrystallized from ethanol to obtain 240 g of the title compound in the form of colorless needle crystals.

Touch point (0C) 2131-132 NMR (CDCI,) δ: 9.60 (b-s, I
H), 7.50 (m, 8H).

3.83 (s, 3H), 3.80 (s, 3
H) Synthesis of oxime 2.57 y (0.01 mol) of 4,4-dimethoxybenzophenone oxime obtained in (1) was dissolved in 51 rLL of dimethylformamide, and 1.2 g of potassium tert-butoxide was added under water cooling. Stir for a minute. To this was added 1.8 g of ethyl-4-chloroacetitrate, and the mixture was stirred at room temperature. After 2 hours, the reaction solution was poured into dilute hydrochloric acid and extracted with ethyl alcohol. Purification of the crude product by silica gel column chromatography yields 3.1
g of the title compound is obtained.

ONMR (CDCl5) δ: 6.7-7.4 (8H), 4.6 (2)r) 3
．． 9-4.2 (2H) 3.8 (6H) 3.5 (
2H), 1.2 (3H) Example 2 3.85 g of 4,4'-dimethoxybenzophenone and 0-(3-ethoxycarbonyl-2=oxopropyl)oxime obtained in Example 1 were dissolved in 5 ml of pyridine. 1 g of methoxylamine hydrochloride was added thereto, and the mixture was stirred at room temperature. After 2 hours, the reaction solution was poured into ethyl acetate, washed with dilute hydrochloric acid and saturated brine, and purified by silica gel chromatography to obtain 4 g of the title compound as a colorless oil.

o NMR (CDCI,) δ: 6.7-7.4 (8H), 5.0.4.7 (2H
>.

3.8-4.2 (2H) 3.8 (9H) 3.3
．． 3.4 (2H) 1.0-1.2 (3H) Example 3 Oxime 4,4'-dimethoxybenzophenone, 0-(3-ethoxycarbonyl-2-methoxyiminopropyl)oxime obtained in Example 2 4.14. was dissolved in 20 rnL of methanol, and added with 3 mL of 5N sei soda aqueous solution.
ml and stirred at room temperature for 5 hours.

After the reaction was completed, the reaction solution was made acidic with dilute hydrochloric acid.

Extraction with ethyl acetate gives 3.8 g of the title compound as a colorless oil.

ONMR (CDCl,) δ: 9.50 (IH),
6.8-7.5 (8H).

5.0.6.8 (2H), 3.8-3.9 (9H),
3.5°3.3 (2H) Example 4 Instead of ethyl-4-chloroacetoacetate, 4-
Using 2.2 g of bromo-4-cyanobutyric acid ethyl ester, 3.6 g of the title compound having the following physical properties was obtained according to the method of Example 1.

o NMR (CDC1a) δ: 6.8-7.5 (8
H), 5.0 (tH).

4.0-4.3 (2H), 3.8 (6H).

2.2-2.6 (4H), 1.2 (3H) Example 5 4,4'-dimethoxybenzophenone obtained in Example 4, 0-(1-cyano-3-ethoxycarbonylpropyl)oxime 3 .96 is dissolved in 20 rrtL of dioxane, 3 mL of 5N aqueous sodium hydroxide solution is added thereto, and the mixture is reacted at 60° C. for 5 hours.

After the reaction is completed, the two reaction solutions are acidified and extracted with ethyl acetate to obtain 3.6 g of the title compound as a colorless oil.

ONMR (CDCI,) δ: 6.7-7.5 (8H), 5.0 (IH) 3.
8 (6H) 2.1-2.7 (4H) Example 6 Instead of ethyl-4-chloroacetoacetate, 5-
Bromo-5-cyanopentanoic acid methyl ester 2.2g
The reaction and treatment were carried out in accordance with the method of Example 1 using 3.7 g of the title compound having the following physical properties.

o NMR (CDCl,) δ: 6.8-7.6 (8
H), 4.9 (LH).

3.8 (6H), 3.6 (3H), 2.4 (2H)
.

1.6-2.2 (4H) Example 7 A reaction was carried out according to the method of Example 5 to obtain the title compound having the following physical properties.

o NMR (CDC δ: 6.7-7.5 (8H)
, 4.9 (IH).

3.8 (6H), 2.4 (2H).

1.6-2.2 (4H)

Claims (14)

[Claims] (1) General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R^1 and R^2 mean the same or different hydrogen atoms or lower alkoxy groups. X is a group represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (in the formula, R^3 means a hydrogen atom or a lower alkyl group), a group represented by the formula ▲
There are mathematical formulas, chemical formulas, tables, etc. Groups represented by ▼ (in the formula, R^5 means a hydrogen atom or a lower alkyl group, and R^4 means a lower alkyl group), formulas ▲ Numerical formulas, chemical formulas, tables, etc. There is a group represented by ▼ (in the formula, R^6 means a hydrogen atom or a lower alkyl group, and n means an integer of 1 to 3), or a group represented by the formula -(CH_2)m-Y (in the formula, Y is a group represented by the formula -SH, a group represented by the formula -SCN, or a 5- or 6-membered ring which may be substituted with a ring having one or more nitrogen or sulfur atoms in the ring. m means a monovalent group derived from m means an integer of 1 to 2). ] Substituted benzophenone oxime ether derivatives and pharmacologically acceptable salts thereof. (2) Both R^1 and R^2 are lower alkoxy groups, and X is a formula ▲ has a mathematical formula, chemical formula, table, etc. ▼ (in the formula, R^3 means a hydrogen atom or a lower alkyl group) Substituted benzophenone oxime ether derivatives according to claim 1, which are the groups shown, and pharmacologically acceptable salts thereof. (3) Both R^1 and R^2 are lower alkoxy groups, and X is a formula ▲ Numerical formula, chemical formula, table, etc. The substituted benzophenone oxime ether derivative and its pharmacologically acceptable salt according to claim 1, wherein ^4 means a lower alkyl group. (4) Both R^1 and R^2 are lower alkoxy groups, and X is a formula ▲ Numerical formula, chemical formula, table, etc. means an integer of 1 to 3)
Substituted benzophenone oxime ether derivatives and pharmacologically acceptable salts thereof as described in 1. (5) Both R^1 and R^2 are lower alkoxy groups, and X is the formula -(CH_2)_m-Y (wherein Y is the formula -
A ring derived from a group represented by SH, a group represented by the formula -SCN, or a 5- or 6-membered ring which may be substituted with a ring having one or more nitrogen or sulfur atoms in the ring. means a group of valence. m means an integer of 1-2. ) The substituted benzophenone oxime ether derivative according to claim 1, which is a group represented by: (6) Both R^1 and R^2 are methoxy groups, and X is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^ in the formula
The substituted benzophenone oxime ether derivative and its pharmacologically acceptable salt according to claim 1, wherein 5 represents a hydrogen atom or a lower alkyl group. (7) The substituted benzophenone oxime ether derivative according to claim 1, wherein R^1 and R^2 are both methoxy groups, and X is the formula ▲ Numerical formula, chemical formula, table, etc. ▼ and its pharmacology acceptable salt. (8) Both R^1 and R^2 are methoxy groups, and X is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^ in the formula
6 means a hydrogen atom or a lower alkyl group, and n means an integer of 1 to 3. salt. (9) The substituted benzophenone oxime ether derivative according to claim 1, wherein R^1 and R^2 are both methoxy groups, and X is the formula ▲ Numerical formula, chemical formula, table, etc. ▼ and its pharmacology acceptable salt. (10) The substituted benzophenone oxime ether derivative according to claim 1, wherein R^1 and R^2 are both methoxy groups, and X is the formula ▲ Numerical formula, chemical formula, table, etc. ▼ and its pharmacology acceptable salt. (11) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 and R^2 mean the same or different hydrogen atoms or lower alkoxy groups). Hal-X [wherein,
Hal means a halogen atom, and X is a group represented by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. There are tables, etc. ▼ (In the formula, R^5 means a hydrogen atom or a lower alkyl group, R^
4 means a lower alkyl group), formula ▲ Numerical formula, chemical formula, table, etc. or a group represented by the formula -(CH_2)m-
Y (wherein Y is a group represented by the formula -SH, a group represented by the formula -SCN, or a 5-membered ring which may be substituted with a ring having one or more nitrogen or sulfur atoms in the ring) or a monovalent group derived from a 6-membered ring.m is 1-
means an integer of 2. ) means a group represented by ] is subjected to a condensation reaction with a halogen compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2 and X have the above meanings)
A method for producing a substituted benzophenone oxime ether derivative or a pharmacologically acceptable salt thereof, which comprises obtaining a substituted benzophenone oxime ether derivative represented by the formula, and optionally subjecting the obtained substituted benzophenone oxime ether derivative to a salt formation reaction. . (12) General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R^1 and R^2 mean the same or different hydrogen atoms or lower alkoxy groups. A is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^ in the formula
3 means a lower alkyl group), a group represented by the formula ▲ numerical formula,
There are chemical formulas, tables, etc. ▼ (In the formula, R^5 means a lower alkyl group, R^4 means a lower alkyl group) or formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( In the formula, R^6 means a lower alkyl group, n means an integer of 1 to 3)] is hydrolyzed to form the general formula ▲ mathematical formula, chemical formula, table etc.▼ [In the formula, R^1 and R^2 mean the same or different hydrogen atoms or lower alkoxy groups. B is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^ in the formula
There are groups, formulas, formulas, mathematical formulas, chemical formulas, tables, etc. (where R^5 means a hydrogen atom and R^4 means a lower alkyl group) (where R^5 means a hydrogen atom and R^4 means a lower alkyl group). or a group represented by the formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^6 means a hydrogen atom and n means an integer from 1 to 3). A method of obtaining a substituted benzophenone oxime ether derivative or a pharmacologically acceptable salt thereof, wherein the substituted benzophenone oxime ether derivative is obtained by subjecting the obtained substituted benzophenone oxime ether derivative to a salt formation reaction if necessary Production method. (13) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 and R^2 mean the same or different hydrogen atoms or lower alkoxy groups. R^5 is a hydrogen atom or lower alkyl group ) to the compound represented by
By reacting with an amine compound represented by the general formula H_2N-OR^4 (R^4 means a lower alkyl group), the general formula ▲ has numerical formulas, chemical formulas, tables, etc. ▼ (in the formula R^1, R ^2, R^4 and R^5 have the above-mentioned meanings), and if necessary, the obtained substituted benzophenone oxime ether derivative is subjected to a salt-forming reaction. A method for producing the benzophenone oxime ether derivative or a pharmacologically acceptable salt thereof. (14) General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R^1 and R^2 mean the same or different hydrogen atoms or lower alkoxy groups. X is a formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (R^ in the formula
3 means a hydrogen atom or a lower alkyl group) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^5 means a hydrogen atom or a lower alkyl group, R^
4 means a lower alkyl group), formula ▲ Numerical formula, chemical formula, table, etc. ), or a group represented by the formula -(CH_2)_m-Y (where Y is a group represented by the formula -SH, a group represented by the formula -SCN, or a group having one nitrogen or sulfur atom in the ring or means a monovalent group derived from a 5-membered ring or a 6-membered ring which may be substituted with one or more rings; m means an integer of 1 to 2) . ] An antiplatelet/antithrombotic agent containing a substituted benzophenone oxime ether derivative represented by the following and a pharmacologically acceptable salt thereof as an active ingredient.