JPH0224269B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION Technical Field The present invention relates to a novel pyridine derivative and a thromboxane A ₂ synthase inhibitor containing the same. The pyridine derivative provided by the present invention is a new compound and has a strong thromboxane A ₂ synthetase inhibitory effect. Thromboxane A, a metabolite of arachidonic acid ₂
(TXA ₂ ) is produced by the action of thromboxane A ₂ synthetase and has strong physiological effects such as platelet aggregation, vasoconstriction, and bronchoconstriction, and is associated with the onset of angina pectoris, myocardial infarction, cerebral infarction, and bronchial asthma. is known to be involved. Therefore, the compounds of the present invention are effective in preventing these diseases. Furthermore, platelet aggregation is known to be involved in cancer metastasis, and the compounds of the present invention are also expected to be effective in preventing cancer metastasis. Prior art Methylimidazole has been shown to have thromboxane _A2 synthesis inhibitory activity [Prostaglandins, Vol. 13, No.
611-618 (1977)], several other imidazole derivatives have been found to be antithrombotic agents that exhibit thromboxane _A2 synthesis inhibitory activity, but they do not necessarily show satisfactory antithrombotic effects. It's hard to say. Purpose of the Invention As a result of synthesizing various pyridine derivatives, the present inventors discovered that the pyridine derivative according to the present invention has an excellent thromboxane A ₂ synthetase inhibitory effect, leading to the completion of the present invention. Therefore, an object of the present invention is to provide a novel pyridine derivative and a thromboxane A ₂ synthetase inhibitor containing the same. The pyridine derivative according to the present invention has a strong platelet aggregation inhibitory effect, vasoconstriction inhibitory effect, and bronchoconstriction inhibitory effect, and is effective against diseases caused by platelet aggregation, vasoconstriction, and bronchoconstriction, such as angina pectoris, myocardial infarction, and cerebral infarction. It is useful as a preventive agent for asthma, etc. The object of the present invention is achieved by the configuration shown below. That is, the present invention is based on the general formula () [In the formula, R ¹ represents () a hydrogen atom, () a linear or branched alkyl group having 1 to 5 carbon atoms, () a phenyl group or a substituted phenyl group, and the substituted phenyl group has 1 to 5 carbon atoms. may contain one or two identical or different substituents selected from the group consisting of a straight or branched alkyl group, an alkoxy group having 1 to 2 carbon atoms, fluorine, chlorine, or bromine. X represents a single bond or a carbonyl group, m
represents 1 or 2; however, when X is a carbonyl group, m represents 1. n represents an integer from 0 to 6, and Y represents the formula -OCH ₂ CO ₂ R ² or -CO ₂ R ²
(In the formula, ^R2 represents a hydrogen atom or a linear or branched alkyl group having 1 to 3 carbon atoms.) ]
It is a pyridine derivative represented by Furthermore, the present invention provides the general formula () [In the formula, R ¹ represents () a hydrogen atom, () a linear or branched alkyl group having 1 to 5 carbon atoms, () a phenyl group or a substituted phenyl group, and the substituted phenyl group has 1 to 5 carbon atoms. may contain one or two identical or different substituents selected from the group consisting of a straight or branched alkyl group, an alkoxy group having 1 to 2 carbon atoms, fluorine, chlorine, or bromine. X represents a single bond or a carbonyl group, m represents 1 or 2, and m represents 1 when X is a carbonyl group. n represents an integer from 0 to 6, Y represents the formula -
It represents OCH ₂ CO ₂ R ² or -CO ₂ R ² (wherein R ² represents a hydrogen atom or a straight or branched chain alkyl group having 1 to 3 carbon atoms). This is a thromboxane A ₂ synthetase inhibitor containing a pyridine derivative shown in ]. In the present invention, a thromboxane A ₂ synthetase inhibitor refers to a preparation that inhibits the action of thromboxane A ₂ synthetase. Specific Description of the Invention The pyridine derivative of the present invention has the following formula () (In the formula, the definition of R ¹ is the same as the formula ()) in tetrahydrofuran, benzene, dimethoxyethane or dimethylformamide, or in a mixed solvent obtained by appropriately mixing these solvents. ) (In the formula, n represents an integer of 0 to 6, and R ³ represents a methyl group, ethyl group, propyl group, isopropyl group, butyl group or tert-butyl group) or a phosphonate derivative represented by the general formula () (In the formula, R ⁴ represents a methyl group or an ethyl group) Compounds obtained by reacting using sodium hydrogen (NaH) and pyridine of the formula () lead to derivatives. The pyridine derivative of the present invention is thromboxane A ₂
Active ingredient or one of the active ingredients of a synthetic enzyme inhibitor
Thromboxane A2 can be used as a preventive agent for diseases caused by thromboxane _A2 , but it is particularly used as a preventive agent for angina pectoris, myocardial infarction, cerebral infarction, asthma, and cancer metastasis. Daily amount approx.
The dose is 10 to 800 mg, preferably administered in 1 to 3 doses if necessary. The method of administration can take any form suitable for administration, with oral administration being particularly preferred, although intravenous injection is also possible. The compound of the present invention may be formulated into tablets, powders, capsules, or granules either alone or mixed with pharmaceutical carriers or excipients in a conventional manner. Examples of carriers or excipients include calcium carbonate, calcium phosphate, starch, sucrose, lactose, talc, magnesium stearate, and the like. In addition to the solid formulations mentioned above, the compounds of the present invention can also be formulated into liquid formulations such as oily suspensions and syrups. The compound of the present invention can also be stabilized by inclusion with cyclodextrin. EXAMPLES Next, the present invention will be explained in more detail with reference to Examples and Test Examples, but the present invention is not limited thereto. Example 1 Dimethyl methyl phosphate 4.5 under argon atmosphere
ml was dissolved in 210 ml of dry tetrahydrofuran, and 29 ml of n-butyllithium-hexane solution (1.55 M) was added dropwise at -70°C. After reacting at the same temperature for 1 hour, 29 ml of diethyl adipate was added. After reacting at -70°C for 30 minutes, a saturated ammonium chloride aqueous solution was added and the mixture was returned to room temperature. After distilling off tetrahydrofuran under reduced pressure, the resulting residue was extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
41 g of the obtained residue was subjected to silica gel column chromatography, and from the ethyl acetate elution fraction, 7-
4.1 g of ethyl dimethylphosphono-6-oxoheptanoate was obtained. Under an argon atmosphere, 132 mg of oily sodium hydride (content 60%) was suspended in 8 ml of dry benzene, and 764 mg of ethyl 7-dimethylphosphono-6-oxoheptanoate was dissolved in 8 ml of dry benzene under ice cooling.
was added dropwise and stirred for 30 minutes. To this mixture 292 mg of nicotinaldehyde dissolved in 8 ml of dry benzene.
was added dropwise at room temperature and allowed to react for 30 minutes. below freezing,
A saturated ammonium chloride aqueous solution was added to the reaction solution, and extraction was performed with dichloromethane. The organic layer was washed with water, dried with anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. 568 mg of the resulting residue was subjected to silica gel column chromatography, and from the benzene/ethyl acetate 1:1 elution fraction (7E)-6 -Oxo-8-
180 mg of ethyl (3-pyridyl)-7-octenoate was obtained. Under an argon atmosphere, add sodium borohydride to a solution of 168 mg of the compound dissolved in 8 ml of methanol.
56 mg was added at -10°C and reacted for 30 minutes. After adding an excess of acetone under ice-cooling, a saturated aqueous ammonium chloride solution was added, followed by extraction with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a residue of 170
mg was subjected to silica gel column chromatography, and 152 mg of ethyl (7E)-6-hydroxy-8-(3-pyridine)-7-octenoate was obtained from the ethyl acetate elution fraction. Under an argon atmosphere, 848 mg of triethylamine was added to a solution of 111 mg of the compound dissolved in 9 ml of dry tetrahydrofuran under ice cooling, and then 481 mg of methanesulfonyl chloride was added dropwise. Mix this mixture at room temperature for 16
After reacting for an hour, saturated aqueous sodium hydrogen carbonate solution was added under ice cooling, and extraction was performed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and 110 mg of the resulting residue was subjected to silica gel column chromatography.
7E) 60 mg of ethyl-8-(3-pyridyl)-5,7-octadienoate was obtained. Under an argon atmosphere,
To 54 mg of the compound dissolved in 3 ml of ethanol, 420 μl of a 2N aqueous potassium hydroxide solution was added at room temperature and reacted for 3 hours. Under ice cooling, add hydrochloric acid aqueous solution to neutralize,
Extraction was performed with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. 45 mg of the resulting residue was subjected to silica gel column chromatography, and from the ethyl acetate elution fraction (5E, 7E) -8- (3-pyridyl)-5,7
-33 mg of octadienoic acid () was obtained. The infrared absorption spectrum data and mass spectrometry data of this product are shown below. IRν ^KBr _nax (cm ^-1 ): 1710 MS (m/z): 217 (molecular ion peak), 158,
144,92 Example 2 Obtained by the same method as Example 1 (7E)
To a solution of 140 mg of ethyl -6-oxo-8-(3-pyridyl)-7-octenoate dissolved in 15 ml of ethanol under an argon atmosphere, 2 ml of a 1N aqueous sodium hydroxide solution was added at room temperature and reacted for 2 hours.
Under ice-cooling, an aqueous hydrochloric acid solution was added to the reaction solution to neutralize it, and the mixture was extracted with chloroform. Wash the organic layer with water,
After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and 50 mg of the resulting residue was subjected to silica gel column chromatography.
From the 99:1 elution fraction (7E)-6-oxo-8-
45 mg of (3-pyridyl)-7-octenoic acid () was obtained. The infrared absorption spectrum data and mass spectrometry data of this product are shown below. IRν ^KBr _nax (cm ^-1 ): 1710, 1690 MS (m/z): 233 (molecular ion peak), 174,
146, 132, 104 Example 3 50% oily sodium hydride under argon atmosphere
To a suspension of 3.93 g of dry tetrahydrofuran (100 ml) was added 18.2 ml of triethyl-4-phosphonocrotonate in dry tetrahydrofuran (50 ml) under ice cooling.
The solution was added dropwise over a period of 25 minutes and then stirred for 1 hour. 3-
A solution of 10.0 g of benzoylpyridine in dry tetrahydrofuran (50 ml) was added dropwise over a period of 20 minutes, and the mixture was allowed to react at room temperature for 16 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture under ice cooling, and extraction was performed with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue of 26.5
g was subjected to alumina column chromatography,
5-phenyl-5-(3-
9.605 g of ethyl pyridyl-2,4-pentadienoic acid ester was obtained. 8.00 g of the compound water-methanol (4:5)
5.73 g of sodium hydroxide was added to the 180 ml solution and heated under reflux for 2 hours. After methanol was distilled off under reduced pressure, it was diluted with water and washed with ether. Cool the aqueous layer on ice.
After adjusting the pH to 4 with a 3N aqueous hydrochloric acid solution, extraction was performed with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue.
7.985g was subjected to silica gel column chromatography, and from the chloroform:methanol (99:1) elution fraction, (2E,4E)-5-phenyl-5-
3.24 g of (3-pyridyl)-pentadienoic acid was obtained.
Also, chloroform to methanol (99 to 1 to 97
3) From the elution fraction, 3.15 g of (2E,4Z)-5-phenyl-5-(3-pyridyl)pentadienoic acid was obtained, and the structure of this product was recrystallized from methanol-acetone, and the single crystal X-ray structure Determined by analysis. That is, the crystal system is orthorhombic, the space group is P2,
2,2, the size of the lattice is a=10.124Å, b=
19.510 Å, c = 6.925 Å, and the number of structural units in the lattice was 4. The physicochemical data of these compounds support the structures of the following formulas () and (), respectively. MS (m/e): 251 (molecular ion peak), 206 IRν ^KBr _nax cm ^-1 : 1700 ¹ H-NMR (heavy pyridine) δppm: 6.47 (1H,
d, J=15Hz), 6.96 (1H, d, J=12Hz) ^1H -NMR (heavy pyridine) δppm: 6.40 (1H,
d, J = 14.5Hz), 6.97 (1H, d, J = 11.5
Hz) Example 4 Under an argon atmosphere, 729 mg of (2E,4E)-5-phenyl-5-(3-pyridyl)pentadienoic acid was dissolved in 14 ml of dry methanol, 886 μl of trimethylsilyl chloride was added at room temperature, and the mixture was reacted for 17 hours. . Add 586 mg of sodium hydrogen carbonate to the reaction solution under ice cooling.
After adding 15 ml of an aqueous solution and stirring, extraction was performed with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue of 810 mg.
was subjected to silica gel column chromatography,
From the chloroform elution fraction, 736 mg of (2E,4E)-5-phenyl-5-(3-pyridyl)pentadienoic acid methyl ester was obtained. A solution of 1.5 M diisobutylaluminum hydride in toluene (4.7 mL) at -40°C in a solution of 730 mg of the compound in dry toluene (15 mL) under an argon atmosphere.
ml and stirred for 30 minutes. Add methanol 6 to the reaction solution
ml was added, the temperature was returned to room temperature, water and ethyl acetate were added, and after stirring for 30 minutes, insoluble matter was suction-filtered, and the filtrate was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a residue 732
mg of benzene to ethyl acetate (1:4 to 1:1) was subjected to silica gel column chromatography.
From the elution fraction, (2E,4E)-5-phenyl-5-
(3-pyridyl)pentadien-1-ol 626mg
I got it. Under an argon atmosphere, 89 mg of tetrabutylammonium hydrogen sulfate and 2.6 ml of a 50% aqueous sodium hydroxide solution were added to a solution of 622 mg of the compound in 12 ml of methylene chloride at room temperature and stirred. A solution of 435 mg of bromoacetonitrile in methylene chloride (3 ml) was added dropwise over 2 minutes, and the mixture was reacted for 2.5 hours. After making the reaction solution neutral with a 2N aqueous hydrochloric acid solution under ice cooling,
Extraction was performed with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. 948 mg of the resulting residue was subjected to silica gel column chromatography, and benzene:ethyl acetate (95:5 to 9:1) From the elution fraction,
(2E,4E)-5-phenyl-5-(3-pyridyl)pentadiene-1-oxyacetonitrile
Obtained 395mg. Under an argon atmosphere, 86% potassium hydroxide was added to a solution of 393 mg of the compound in 12 ml of water-ethanol (1:2).
662 mg was added and heated under reflux for 30 minutes. The reaction solution was adjusted to pH 4 with a 1N aqueous hydrochloric acid solution under ice cooling, and then extracted with chloroform:methanol (4:1). The organic layer was washed with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and 320 mg of the resulting residue was subjected to silica gel column chromatography. 2E, 4E)-5-phenyl-5-(3-
200 mg of pentadiene-1-oxyacetic acid (pyridyl) was obtained. The weight and infrared absorption spectrum data of this product are shown below. MS (m/z): 295 (molecular ion peak), 208,
206 IRν ^neat _nax cm ^-1 :1720 Example 5 By the same method as in Example 4, (2E, 4Z) -5
-Phenyl-5-(3-pyridyl)pentadienoic acid ( ), (2E,4Z)-5-phenyl-5-
(3-pyridyl)pentadiene-1-oxyacetic acid () was obtained. The weight and infrared absorption spectrum data are shown below. MS (m/z): 295 (molecular ion peak), 208,
206 IRν ^neat _nax cm ^-1 : 1730 Example 6 Under an argon atmosphere, 155 mg of oily sodium hydride (content 60%) was suspended in 10 ml of dry tetrahydrofuran, and 7-dimethylphosphono- 1.1 g of ethyl 6-oxoheptanoate was added dropwise and stirred for 30 minutes.
To this mixture was added 567 mg of 3-benzoylpyridine dissolved in 10 ml of dry tetrahydrofuran,
The mixture was heated to reflux for an hour. A saturated ammonium chloride aqueous solution was added to the reaction mixture under ice cooling, and extraction was performed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a residue.
1.421 g was subjected to silica gel column chromatography, and the less polar isomer of ethyl 6-oxo-8-phenyl-8-(3-pyridyl)-7-octenoate ( 345 mg of XI) and 262 mg of the highly polar isomer (XII) were obtained. The nuclear magnetic resonance spectrum data of these compounds (XI) and (XII) are shown below. ¹ H-NMR (deuterated chloroform) δ (ppm): 1.23
(3H, t, J = 7Hz), 4.10 (2H, q, J =
7Hz), 6.69 (1H, s) ^1H -NMR (deuterated chloroform) δ (ppm): 1.19
(3H, t, J = 7Hz), 4.06 (2H, q, J =
7 Hz), 6.48 (1 H, s) Under an argon atmosphere, 1.6 ml of a 1N aqueous sodium hydroxide solution was added to 130 mg of the compound (XI) dissolved in 10 ml of ethanol at room temperature, and the mixture was allowed to react for 2 hours. The mixture was neutralized with an aqueous hydrochloric acid solution under ice cooling, and extracted with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 90 mg of one isomer, 6-oxo-8-phenyl-8-(3-pyridyl)-7-octenoic acid (). Ta. The mass spectrometry data of this product is shown below. MS (m/z): 309 (molecular ion peak), 208,
180 The other isomer, 6-oxo-8-phenyl-8-(3-pyridyl)-7-octynic acid (XI), was obtained from compound (XII) in a similar manner. The mass spectrometry data of this product is shown below. MS (m/z): 309 (molecular ion peak), 208,
180 Example 7 6-oxo-8-phenyl-8-(3
90 mg of sodium borohydride was added to a solution of 363 mg of ethyl (pyridyl)-7-octenoate dissolved in 18 ml of methanol at -10°C, and the mixture was reacted for 20 minutes. After adding an excess of acetone under ice-cooling, a saturated aqueous ammonium chloride solution was added and extraction was performed with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. 360 mg of the resulting residue was subjected to silica gel column chromatography, and 6-hydroxy was extracted from the benzene/ethyl acetate 1:1 elution fraction. 329 mg of ethyl -8-phenyl-8-(3-pyridyl)-7-octenoate was obtained. Under an argon atmosphere, 309 mg of the compound was dissolved in 6 ml of dry dimethyl sulfoxide and heated under reflux for 2 hours. After evaporating the solvent under reduced pressure, the resulting residue was subjected to silica gel column chromatography, and benzene/
8-Phenyl- from the 3:1 ethyl acetate elution fraction
102 mg of a low polar isomer ( ) and 96 mg of a high polar isomer ( ) of ethyl 8-(3-pyridyl)-5,7-octadienoate were obtained. Under an argon atmosphere, 1 ml of a 1N aqueous sodium hydroxide solution was added to 88 mg of the compound () dissolved in 8 ml of ethanol at room temperature, and the mixture was allowed to react for 3 hours. The mixture was neutralized with an aqueous hydrochloric acid solution under ice cooling, and extracted with chloroform. After washing the organic layer with water and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain a residue of 80%
8-phenyl-8-(3-pyridyl)-5, 8-phenyl-8-(3-pyridyl)-5,
72 mg of 7-octadienoic acid () was obtained. The infrared absorption spectrum and mass spectrometry data of this product are shown below. IRν ^neat _nax cm ^-1 : 1710 MS (m/z): 293 (molecular ion peak), 234,
206 Using the same method, the other isomer 8-phenyl-8-(3-pyridyl)-
5,7-octadienoic acid () was obtained. The infrared absorption spectrum and mass spectrometry data of this product are shown below. IRν ^neat _nax cm ^-1 : 1710 MS (m/z): 293 (molecular ion peak), 234,
206 Test Example Measurement of thromboxane _A2 synthetase inhibitory activity Nine volumes of blood are collected from the abdominal aorta of a rat using a syringe containing 3.8% sodium citrate solution (1 volume). Obtain platelet-rich plasma by centrifugation. Add 1/10 volume of 77mM EDTA to platelet-rich plasma.
Add the solution, mix well, and rotate at 2500 rpm at room temperature.
Perform centrifugation for 10 minutes. Discard the supernatant and add washing solution (sodium chloride 134mM, tris-aminomethane).
15mM EDTA 1mM D-glucose 5mM dissolved in re-distilled water and adjusted to pH 7.4 with 1N hydrogen chloride) Resuspend platelets in approximately 3ml and stir at room temperature.
Centrifuge at 2000 rpm for 10 minutes. Discard the supernatant, resuspend the precipitated platelets in PH8.0 phosphate buffer, and adjust the platelet count to 1×10 ⁶ cells/μl. The thus obtained washed platelets were treated with thromboxane.
Use as a source of _A2 synthase. Alkydonic acid 3μg, ¹⁴ C-labeled arachidonic acid 0.2μCi
(1 μg) into a test tube with a stopper, add one drop of propylene glycol/ethanol mixture (1:3 volume), and evaporate the ethanol under nitrogen gas. Add 50 μl of sample solution to this, and then add 450 μl of washed platelets.
Add and react at 37°C for 3 minutes. While cooling on ice, add 1 drop of 1N hydrogen chloride to bring the pH to 2.
~3. Add 2 ml of ethyl acetate, shake and extract for 10 minutes, and centrifuge at 2500 rpm for 10 minutes at 4°C. After transferring the supernatant to a flask and concentrating it, the residue was dissolved in 100 μl of ethanol and placed on a thin silica gel plate (manufactured by Merck & Co., Ltd.).
Spot the entire amount on 60F ₂₅₄ ). Developing solvent (chloroform/methanol/acetic acid/
After developing for about 18 cm with water = 70:8:1:0.8), measure the radioactivity of thromboxane B ₂ (a non-enzymatic metabolite of thromboxane A ₂ ) using a radiochromatography scanner to determine the inhibitory activity. As a result of the test, remarkable thromboxane A ₂ synthetase inhibitory activity was found as shown in Table 1 below as a representative example. In addition, similar thromboxane derivatives according to the present invention not shown in Table 1
It was confirmed that it has _A2 synthase inhibitory activity.
In addition, the 50% inhibitory concentration in the table means that when the amount of thromboxane A ₂ produced without introducing the pyridine derivative according to the present invention is 100%, the amount of thromboxane A ₂ produced by introducing the pyridine derivative is 50%. It means the concentration of pyridine derivative solution required to suppress the

【table】

【table】

[Table] Acute toxicity An acute toxicity test was conducted by oral administration using ICR male mice (6 weeks old). The LD ₅₀ values of the compounds of the present invention were all 300 mg/Kg or more, confirming high safety. Effects of the Invention According to the present invention, a novel pyridine derivative and a thromboxane A ₂ synthetase inhibitor containing the same are provided. The above compounds of the present invention inhibit the action of thromboxane _A2 synthetase, resulting in thromboxane
Since it significantly inhibits _A2 biosynthesis, it can be used as a prophylactic agent for diseases caused by thromboxane _A2 , such as angina pectoris, myocardial infarction, cerebral infarction, and asthma. Further, although thromboxane A ₂ has a platelet aggregation effect, since platelet aggregation is involved in cancer metastasis, the above-mentioned compound of the present invention can also be used as an agent for preventing cancer metastasis.

Claims (1)

[Claims] 1 General formula () [In the formula, R ¹ represents () a hydrogen atom, () a linear or branched alkyl group having 1 to 5 carbon atoms, () a phenyl group or a substituted phenyl group, and the substituted phenyl group has 1 to 5 carbon atoms. may contain one or two identical or different substituents selected from the group consisting of a straight or branched alkyl group, an alkoxy group having 1 to 2 carbon atoms, fluorine, chlorine, or bromine. X represents a single bond or a carbonyl group, m represents 1 or 2, and m represents 1 when X is a carbonyl group. n represents an integer from 0 to 6, Y represents the formula -
A pyridine derivative represented by OCH ₂ CO ₂ R ² or -CO ₂ R ² (wherein R ² represents a hydrogen atom or a straight or branched alkyl group having 1 to 3 carbon atoms). 2 General formula () [In the formula, R ¹ represents () a hydrogen atom, () a linear or branched alkyl group having 1 to 5 carbon atoms, () a phenyl group or a substituted phenyl group, and the substituted phenyl group has 1 to 5 carbon atoms. may contain one or two identical or different substituents selected from the group consisting of a straight or branched alkyl group, an alkoxy group having 1 to 2 carbon atoms, fluorine, chlorine, or bromine.
X represents a single bond or a carbonyl group, m represents 1 or 2, and m represents 1 when X is a carbonyl group. n represents an integer from 0 to 6, and Y represents the formula -OCH ₂ CO ₂ R ² or -CO ₂ R ² (wherein R ² is a hydrogen atom, a linear or branched alkyl group having 1 to 3 carbon atoms) represents a group). ]
A thromboxane _A2 synthetase inhibitor containing a pyridine derivative represented by: