JPH0514712B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to novel amine derivatives and salts thereof. For more details, see the following general formula [] "In the formula, R ¹ and R ² are the same or different,
Indicates a hydrogen atom or an alkyl group. Furthermore, R ¹ and R ² may form a heterocyclic group together with the nitrogen atom to which they are bonded. A is an alkenylene group, R ³ is a hydrogen atom or an alkyl group, R ⁴ is an aryl group which may have a substituent, p is 1, 2 or 3, X is oxygen or sulfur atom, Y is sulfur atom, q is 2, 3
or 4, and Z represents an alkylene group, respectively. ” and its salts. The present inventors focused on the fact that compounds with histamine H ₂ inhibitory effects are useful for treating peptic ulcers, and as a result of intensive research into compounds that competitively antagonize histamine at H ₂ receptors, The present inventors have discovered that a novel amine derivative represented by the general formula [] and its salt have excellent anti-ulcer effects, leading to the completion of the present invention. Therefore, an object of the present invention is to provide an amine derivative represented by the general formula [] and a salt thereof. The amine derivatives and salts thereof represented by the general formula [ ] of the present invention have a

[Based on M.N.Ghosh and H.O.Schild; Birt.J.Pharmacol., 13.54 (1958)]

Wistar fasted for 18 hours
Rats (male, weighing 200 to 250 g) were anesthetized with urethane, and after laparotomy, the forestomach was incised, the inside of the stomach was sufficiently washed with physiological saline, and the incision was sutured. A silicone tube was inserted approximately 5 mm into the stomach from the duodenal side and fixed. Next, physiological saline adjusted to approximately PH10 with an aqueous sodium hydroxide solution was perfused into the stomach through the oral probe at a constant rate (1 ml/min), and the PH changes of the perfusion solution flowing out from the silicone tube were continuously recorded. did. During this period, histamine 30μ is used as an acid secretion stimulant.
g/Kg/min was continuously infused from the femoral vein at a rate of 0.3 ml/min. The drug was administered intravenously when acid secretion reached a nearly constant level (PH 3.3 ± 0.2), and additional doses were cumulatively administered when the acid secretion suppressive effect of each dose reached a plateau. From the point at which acid secretion is almost completely suppressed by cumulative administration of the drug and the PH value of the effluent perfusion solution becomes almost the same as the PH value before histamine administration,
The duration of action was defined as the time until the PH value reached 4. The number of experimental cases was 3 for each dose. The results are shown in Table-1.

【table】

[According to H. Shay et al.: Gastroenterology, 5, 43 (1945). ]

After fasting 6 to 7 Wistar rats (male, 190 to 230 g) per group for 35 hours, the drug was orally administered, and 2 hours later, the pylorus was ligated under ether anesthesia. Then, the abdominal wall was sutured, and 25 mg/Kg of histamine was immediately administered subcutaneously to the back. Three hours later, the animal was sacrificed, the cardia was ligated, and the stomach was removed. The gastric juice was centrifuged and the amount of gastric juice was measured. 1 ml of this gastric fluid was titrated with a 0.1N aqueous sodium hydroxide solution with pH 7.0 as the end point. 0.5% Tween for control group
80 water was administered. The gastric juice secretion suppression rate was calculated using the following formula. Suppression rate of gastric acid secretion (%) = Acid production amount of the control group - Acid production amount of the medicinal effect administration group / Acid production amount of the control group x 100 The results are shown in Table 2.

【table】

[Table] [Indomesacin ulcer] After fasting 7 Wistar rats (male, 200-230 g) in one group for 24 hours, the drug was orally administered, and 30 minutes later, indomesacin 30
mg/Kg was injected subcutaneously. After 5 hours, the animal was sacrificed, the stomach was removed, and the stomach was fixed with 1% formalin. The length of the ulcer that had developed in the stomach was measured using a stereomicroscope, and the sum of the lengths was calculated as the ulcer coefficient. The control group received 0.5% Tween 80 water.
The suppression rate was calculated using the following formula. Inhibition rate (%) = Ulcer coefficient of control group - Ulcer coefficient of drug administration group / Ulcer coefficient of control group x 100 The results are shown in Table 3.

[Table] [Acute Toxicity] Drug No. 6 was orally administered at 1000 mg/Kg to 5 ICR mice (male, 27-30 g) per group, and observations were made for one week later, with no deaths. Based on Tables 1 to 3 and acute toxicity, the amine derivatives of the general formula [] and their salts have excellent acid secretion suppressing effects, excellent anti-ulcer effects, long duration of action, and low doses. It is clear that it has excellent properties such as being effective, having low toxicity, and a wide safety margin. Next, a method for producing the amine derivative of the general formula [] or a salt thereof will be described. The amine derivative of general formula [] or its salt is
It is manufactured by the following manufacturing method, a method known per se, and a method analogous thereto. [In the formula, Q and Q' are the same or different groups that can be eliminated, R ¹ , R ² , R ³ , R ⁴ , X, Y, Z,
p, q and A have the meanings described above.] Each manufacturing method will be described in detail below. () [] + [] → [] and [] + []
→Step [] Both of these steps can be performed under substantially the same conditions. This production method involves reacting a compound of general formula [] with a compound of general formula [] or a salt thereof, and a compound of general formula [] and a compound of general formula [] or a salt thereof in the presence or absence of a solvent. It is done by certain things. Q and in general formulas [] and []
Examples of the leaving group for Q' include a halogen atom; an alkylthio group; an alkylsulfinyl group; an aralkylthio group such as benzylthio;
Alkoxy group; 1-imidazolyl group; 3,5-
Commonly known leaving groups such as dimethylpyrazolyl group can be mentioned. Examples of the salts of the compounds of the general formulas [] and [] include the salts exemplified in the case of the salts of the amine derivatives of the general formula [], but in the case of acid addition salts, for example, alkali metals such as sodium methoxide It is preferable to use it in a free state by treating it with an appropriate base such as an alkoxide, an alkali hydroxide such as potassium hydroxide or sodium hydroxide, or an alkali carbonate such as potassium carbonate or sodium carbonate. The solvent is not particularly limited as long as it does not adversely affect the reaction, but examples include alcohols such as methanol, ethanol, isopropanol, and ethylene glycol; nitriles such as acetonitrile and propionitrile; diethyl ether, diisopropyl ether, ，
2-dimethoxyethane, tetrahydrofuran,
Ethers such as dioxane; methylene chloride,
Halogenated hydrocarbons such as chloroform and 1,2-dichloroethane; benzene, toluene,
Aromatic hydrocarbons such as xylene; Amides such as N,N-dimethylformamide and N,N-dimethylacetamide; Dimethylsulfoxide; Pyridine; Solvents such as water are used alone or in combination of two or more of these. be able to. Furthermore, in carrying out this reaction, it may be preferable to use a base or a heavy metal salt.
Such bases include alkali hydroxides such as potassium hydroxide and sodium hydroxide; alkali carbonates such as potassium carbonate and sodium carbonate;
Examples include inorganic bases such as alkali hydrogen carbonates such as potassium hydrogen carbonate and sodium hydrogen carbonate, and tertiary amines such as triethylamine, N-methylmorpholine, N-methylpiperidine, and pyridine. The base can also be replaced by using an excess of a compound of the general formula [] or [] or a salt thereof.
Examples of heavy metal salts include silver nitrate, lead(II) acetate, and mercuric acetate. Some of these raw material compounds exist as geometric isomers, tautomers, optical isomers, and racemates, and any of these isomers can be used in this method. In particular, since the compound of the general formula [] or a salt thereof has an asymmetric carbon in its molecule, when obtaining an optically active form of the amine derivative of the general formula [] or a salt thereof, the compound of the general formula [] It is preferable to use an optically active form of or a salt thereof. The amount of the compound represented by the general formula [] to be used is preferably at least equimolar to the compound represented by the general formula [] or a salt thereof. The reaction temperature and reaction time in the reaction of the compound of general formula [] or its salt with the compound of general formula [] are not particularly limited and are appropriately selected depending on the reaction reagent, etc., but are usually -30 to 40°C. , can be completed in 10 minutes to 48 hours. The obtained compound of general formula [] can also be used in the next reaction without being isolated. Further, the amount of the compound of general formula [] or a salt thereof to be used is preferably equal to or more than the amount of the compound of general formula []. The reaction temperature and reaction time in the reaction of the compound of general formula [] with the compound of general formula [] are not particularly limited and are appropriately selected depending on the reaction reagent, etc., but the reaction is usually carried out at -5 to 200°C,
Preferably, it is carried out at 5 to 120°C and completed in 10 minutes to 48 hours. () Process of [] + [] → [] This production method involves reacting the compound of the general formula [] or its salt with the compound of the general formula [] or its salt in the presence or absence of a solvent. It is done by folding. Examples of the salts of the compound of general formula [] include salts with alkali metals such as potassium and sodium; salts with alkaline earth metals such as calcium and magnesium; and salts with tertiary amines such as triethylamine. The solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, but specific examples include the solvents exemplified in the previous route (). The compound of general formula [] or a salt thereof is preferably used in an amount equal to or more than the same mole relative to the compound of general formula [] or a salt thereof. The reaction temperature and reaction time are not particularly limited and are appropriately selected depending on the reaction reagent, etc., but the reaction is usually carried out at -5 to 200°C, preferably at -5 to 200°C.
It is carried out at 20 to 120°C and is completed in 10 minutes to 48 hours. Note that the raw material compounds of the general formulas [], [], [], [], and [] in each of the above-mentioned production methods, as well as their salts, include new compounds, but methods known per se, the examples and references described below, It is easily produced by the methods described in the examples and methods analogous thereto. The amine derivative of the general formula [] or a salt thereof thus obtained can be easily isolated and collected by conventional operations such as recrystallization, concentration, extraction, optical resolution, column chromatography, etc. Furthermore, the salt of the amine derivative of the general formula [] is
It can be easily obtained from the educt by conventional methods. The anti-ulcer agent containing the amine derivative of the general formula [] or a salt thereof is, for example, a tablet, a hard capsule, a soft capsule, a granule, a powder, a fine granule, a pill, a troche, an ointment, a suppository, injections, suspensions,
It can be prepared in the form of emulsions, drops, syrups, etc. by conventional methods and administered by oral or parenteral routes, with oral administration being particularly preferred. For formulation into various forms suitable for oral or parenteral administration, commonly used non-toxic excipients;
It can be formulated using additives such as binders, lubricants, disintegrants, suppository substrates, and if necessary, isotonic agents, stabilizers, dispersants, antioxidants, etc.
Additives such as colorants, flavoring agents, buffering agents, etc. may also be used. It may also contain other therapeutically useful agents. The dosage of the amine derivative of general formula [] or its salt is generally 0.001 mg/Kg to 10 mg/Kg once to 4 times per day for adults by oral or parenteral administration, but depending on the route of administration, The dosage and frequency of administration will be changed as appropriate depending on the patient's symptoms. Next, the present invention will be explained with reference to Examples and Reference Examples, but the present invention is not limited thereto. Example 1 (1) 20.0 g of 2-thiophene acrolein is dissolved in 180 ml of ethanol, and 18.1 ml of pyrrolidine is added at -5 to 0°C while stirring. Then, 1.5 g of sodium borohydride is added in portions at the same temperature, and the mixture is allowed to react at the same temperature for 1 hour. The solvent was distilled off under reduced pressure, and 200 ml of 1N hydrochloric acid and 50 ml of ethyl acetate were added to the resulting residue to dissolve it, and the pH was adjusted to 2 with 6N hydrochloric acid. Separate the aqueous layer, add 20ml of 25% ammonia water and 200ml of ethyl acetate,
The organic layer is separated, washed with 100 ml of saturated brine, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. When the obtained oil is distilled under reduced pressure, 2-[3
19.8 g (yield 71%) of -(1-pyrrolidinyl)-1-propenyl]thiophene is obtained. (2) 19.8 g of 2-[3-(1-pyrrolidinyl)-1-propenyl]thiophene was dissolved in 72 ml of anhydrous tetrahydrofuran, and the solution was dissolved at -20°C under a nitrogen stream.
-Butyllithium hexane solution (15% w/w)
Drop 71.7ml. Then, the temperature is raised and the reaction is carried out at room temperature for 2 hours, and then 3.69 g of paraformaldehyde is added in portions while maintaining the solution at 10 to 20°C, and the reaction is carried out at room temperature for 2 hours. Distill the solvent under reduced pressure and add 100 ml of ice water and 200 ml of ethyl ether.
was added, the organic layer was separated, washed with 100 ml of water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained oil was subjected to column chromatography (Wako Gel C-200 silica gel: eluent, chloroform: methanol = 9:
If purified in step 1) and recrystallized with a mixed solvent of isopropyl ether and diethyl ether, 13.5 g of 5-[3-(1-pyrrolidinyl)-1-propenyl]-2-thiophenemethanol having a melting point of 63 to 65°C is obtained. (yield 59%). (3) 2.2 g of 5-[3-(1-pyrrolidinyl)-1-propenyl]-2-thiophenemethanol is dissolved in 22 ml of anhydrous methylene chloride, and 2.13 ml of thionyl chloride is added dropwise at 0 to 5°C. After gradually increasing the temperature and reacting at room temperature for 1 hour, the solvent was distilled off under reduced pressure to obtain oily 2-chloromethyl-5-[3-
2.74 g of (1-pyrrolidinyl)-1-propenyl]thiophene hydrochloride is obtained. (4) Dissolve 5.2 g of sodium metal in 150 ml of ethanol, and dissolve cysteamine hydrochloride under a nitrogen stream.
100ml of ethanol solution containing 11.2g was heated to 0°C.
Drip with. After stirring at the same temperature for 1 hour, Example 1
-2-chloromethyl-5[3-(1) obtained in (3)
20 ml of an ethanol solution containing 13.7 g of -pyrrolidinyl)-1-propenyl]thiophene hydrochloride is added dropwise. After the dropwise addition is completed, the temperature is gradually raised and the mixture is allowed to react at room temperature for 2 hours. Then, the solvent was distilled off under reduced pressure, and 200 ml of diethyl ether was added to the resulting residue.
Add 50 ml of saturated saline and separate the organic layer. The organic layer was washed with 100 ml of water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain oily 2-<{5-[3-(1-pyrrolidinyl)-1-propenyl]-2. -thienyl}methylthio>ethylamine 10 g (yield 72%) are obtained. (5) 2-<{5-[3-(1-pyrrolidinyl)-1-
propenyl]-2-thienyl}methylthio>ethylamine 0.85 g and 2-nitromethylene-
Add 0.62 g of 5-phenyloxazolidine to 5 ml of acetonitrile, and react at room temperature for 6 hours with stirring. The solvent was distilled off under reduced pressure, and the resulting residue was subjected to column chromatography (Wakogel C-
200 silica gel: eluent, chloroform: methanol = 9:1), amorphous N
-(2-hydroxy-2-phenylethyl)-
N′-[2-<{5-[3-(1-pyrrolidinyl)-
1.1 g (yield 75%) of 1-propenyl]-2-thienyl}methylthio>ethyl]-2-nitro-1,1-ethenediamine is obtained. NMR ( _CDCl3 ) δ value: 1.45-1.85 (4H, m), 2.2-2.9 (6H, m), 2.95
~3.60 (4H, m), 3.11 (2H, d), 3.80 (2H,
s), 4.81 (1H, m), 5.91 (1H, dt), 6.45 (1H,
s), 6.50 (1H, d), 6.60 (1H, d), 6.71 (1H,
d), 7.21 (5H, s), 10.38 (1H, bs) Example 2 (1) 2-<{5-[3-(1-pyrrolidinyl)-1-
6.0 g of propenyl]-2-thienyl}methylthio>ethylamine and 7.0 g of 1,1-bis(methylthio)-2-nitroethene are added to 60 ml of acetonitrile, and the mixture is reacted under heating under reflux for 1 hour.
The solvent was then distilled off under reduced pressure, and the resulting residue was subjected to column chromatography (Wakogel C-
After treatment with 200 silica gel (eluent chloroform: methanol = 9:1) and recrystallization with ethanol, 1-methylthio-2-nitro-1-[2-<{5-[ 3-(1
-pyrrolidinyl)-1-propenyl]-2-thienyl}methylthio>ethylamino]ethene6.3
g (yield 74%). NMR ( _CDCl3 ) δ value: 1.60 to 1.95 (4H, m), 2.25 to 2.90 (4H, m),
2.40 (3H, s), 2.72 (2H, t), 3.15 (2H, d),
3.35-3.75 (2H, m) 3.83 (2H, s), 5.97 (1H,
dt), 6.45 (1H, s), 6.51 (1H, d), 6.65 (2H,
m), 10.55 (1H, bs) (2) 1-methylthio-2-nitro-1-[2-<
Add 1.0 g of {5-[3-(1-pyrrolidinyl)-1-propenyl]-2-thienyl}methylthio>ethylamino]ethene and 0.5 g of 1-(4-hydroxyphenyl)-2-aminoethanol to 5 ml of methanol. Dissolve and react under stirring at room temperature for 12 hours. The solvent was distilled off under reduced pressure, and the resulting residue was subjected to column chromatography (Wako Gel C
-200 silica gel: eluent chloroform: methanol = 6:1), amorphous N
-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-N'-[2-<{5-[3-(1-
pyrrolidinyl)-1-propenyl]-2-thienyl}methylthio>ethyl]-2-nitro-1,
1.0 g (yield 79%) of 1-ethenediamine is obtained. NMR ( _d6 -DMSO) δ value: 1.55-2.0 (4H, m), 2.4-2.95 (6H, m), 3.0
~3.65 (6H, m), 3.99 (2H, s), 4.6 (1H,
m), 5.92 (1H, d), 6.49 (1H, s), 6.70,
7.15 (4H, AA′BB′) 6.75 (1H, d), 6.86 (2H,
s) Example 3 The following compound is obtained by carrying out the reaction and work-up in the same manner as in Example 1 or 2. ΓN-[2-hydroxy-2-(3-methoxyphenyl)ethyl]-N'-[2-<{5-[3-(1-
pyrrolidinyl)-1-propenyl]-2-thienyl}methylthio>ethyl]-2-nitro-1,
1-ethenediamine amorphous NMR ( _CDCl3 ) δ value: 1.4-1.9 (4H, m), 2.1-2.85 (6H, m), 2.9
~3.6 (4H, m), 3.08 (2H, d), 3.72 (3H,
s), 3.83 (2H, s), 4.8 (1H, m), 5.90 (1H,
dt), 6.2-7.35 (8H, m), 10.4 (1H, bs) ΓN-[2-hydroxy-2-(3-bromophenyl)ethyl]-N'-[2-<{5-[3-(1 -pyrrolidinyl)-1-propenyl]-2-thienyl}methylthio>ethyl]-2-nitro-1,
1-ethenediamine amorphous NMR ( _CDCl3 ) δ value: 1.45-1.95 (4H, m), 2.25-2.9 (6H, m),
2.95-3.65 (4H, m), 3.12 (2H, d), 3.84
(2H, s), 4.8 (1H, m), 5.90 (1H, dt), 6.48
(1H, s), 6.51 (1H, d), 6.62 (1H, d),
6.72 (1H, d), 7.0-7.6 (4H, m), 10.3 (1H,
bs) ΓN-<2-{[5-(3-dimethylamino-1-
propenyl)-2-thienyl]methylthio}ethyl>-N'-(2-hydroxy-2-phenylethyl)-2-nitro-1,1-ethenediamine amorphous NMR (CDCl ₃ δ value: 2.12 (6H, s ), 2.5-3.05 (2H, m), 2.93
(2H, d), 3.1-3.7 (4H, m), 3.85 (2H, s),
4.90 (1H, m), 5.9 (1H, dt), 6.52 (1H, s),
6.53 (1H, d), 6.66 (1H, d), 6.76 (1H, d),
7.28 (5H, s), 10.30 (1H, bs) ΓN-(2-hydroxy-2-phenylethyl)-
N′-[2-<{5-(3-(1-pyropidinyl)-
1-propenyl]-4-methyl-2-thienyl}
Methylthio>ethyl]-N'-(2-hydroxy-2-phenylethyl)-2-nitro-1,1
- Ethendiamine melting point: 82-84°C NMR ( _CDCl3 ) δ value: 1.42-1.82 (4H, m), 2.10 (3H, s), 2.21-
2.52 (4H, m), 2.52~2.88 (2H, m), 2.92~
3.63 (4H, m), 3.09 (2H, d), 3.79 (2H, s),
4.8 (1H, m), 5.81 (1H, dt), 6.48 (1H, s),
6.50 (1H, d), 6.55 (1H, s), 7.24 (5H, s),
10.30 (1H, bs) ΓN-[2-hydroxy-2-(3-methylphenyl)ethyl]-N'-[2-<{5-[3-(1-pyrrolidinyl)-1-propenyl]-4-methyl −
2-Thienyl}methylthio>ethyl}-2-nitro-1,1-ethenediamine Amorphous NMR ( _CDCl3 ) δ value: 1.35-1.95 (4H, m), 2.13 (3H, s), 2.31
(3H, s), 2.41~2.98 (6H, m), 3.01~3.68
(6H, m), 3.82 (2H, s), 4.85 (1H, m),
5.91 (1H, dt), 6.54 (1H, s), 6.61 (1H, d),
6.63 (1H, s), 7.14 (4H, s), 10.35 (1H, bs) ΓN-<2-{[5-(3-dimethylamino-1-
propenyl)-2-furyl]methylthio}ethyl>-N'-(2-hydroxy-2-phenylethyl)-2-nitro-1,1-ethenediamine amorphous NMR ( _CDCl3 ) δ value: 1.93 (6H, s), 2.65~3.04 (4H, m), 3.14~
3.60 (4H, m), 3.70 (2H, s), 4.84 (1H, m),
5.93-6.23 (4H, m), 6.53 (1H, s), 7.28
(5H, s), 7.50~8.15 (1H, bs), 10.14 (1H,
bs) ΓN-<2-{[5-(3-dimethylamino-1-
propenyl)-2-furyl]methylthio}ethyl>-N'-[2-hydroxy-2-4-fluorophenyl)ethyl]-2-nitro-1,1-
Ethendiamine amorphous NMR ( _CDCl3 ) δ value: 1.98 (6, s), 2.68~3.14 (4H, m), 3.17~
3.64 (4H, m), 3.72 (2H, s), 4.88 (1H, m),
5.94~6.26 (4H, m) 6.56 (1H, s), 6.75~
7.53 (4H, m), 7.73 (1H, bs), 10.17 (1H, bs) Reference example 1 Dissolve 40g of DL-β-hydroxyphenethylamine in 60ml of ethanol and 200ml of xylene,
This solution was added dropwise to a solution of 57.8 g of 1,1-bis(methylthio)-2-nitroethene dissolved in 600 ml of xylene under heating under reflux for 1.5 hours. During the reaction, the low boiling point fraction is gradually distilled off,
Keep the reaction temperature at 130-140°C. After the reaction, crystals are precipitated while stirring under ice cooling. After removing the precipitated crystals and drying them, add 5% aqueous sodium hydroxide solution.
Mix with 200ml. After removing trace amounts of insoluble matter,
Adjust the pH of the liquid to 6 with a 10% acetic acid aqueous solution, and separate the precipitated crystals. By drying the obtained crystals, 34 g of 2-nitromethylene-5-phenyloxazolidine having a melting point of 139-141 DEG C. is obtained. Meanwhile, concentrate the liquid and add 50ml of ethanol to the residue.
and collect the precipitated crystals. The obtained crystals are mixed with 25 ml of 5% aqueous sodium hydroxide solution to remove insoluble materials. Adjust the pH of the liquid to 6 with a 10% acetic acid aqueous solution, collect the precipitated crystals, and dry them to obtain 4.8 g of 2-nitromethylene-5-phenyloxazolidine.
get. NMR ( _d6 -DMSO) 3.65-4.52 (2H, m), 6.05 (1H, t), 6.80
(1H, s), 7.54 (5H, s), 10.1 (1H, bs) In the same manner, the following compounds are obtained. Γ5-(3-methylphenyl)-2-nitromethyleneoxazolidine Melting point: 96-97°C NMR ( _CDCl3 ) δ value: 2.37 (3H, s), 3.69-4.50 (2H, m), 5.79
(1H, t), 6.72 (1H, s), 6.80~7.55 (4H,
m), 7.2 (1H, bs) Γ5-(3-methylphenyl)-2-nitromethyleneoxazolidine Melting point: 105-107℃ NMR ( _d6- DMSO) δ value: 3.64-4.55 (2H, m), 3.87 (3H , s), 6.02
(1H, t), 6.79 (1H, s), 6.9-7.65 (4H, m) Γ5-(4-fluorophenyl)-2-nitromethyleneoxazolidine Melting point: 116-118.5℃ NMR (d ₆ -DMSO) δ Value: 3.48-4.56 (2H, m), 6.10 (1H, dd), 6.80
(1H, s), 7.20-7.85 (4H, m), 10.06 (1H,
bs) Γ5-(3-bromophenyl)-2-nitromethyleneoxazolidine Melting point: 120-121°C NMR ( _CDCl3 ) δ value: 3.76-4.60 (2H, m), 5.93 (1H, t), 6.85
(1H, s), 7.39-7.69 (4H, m), 9.30 (1H,
bs).

Claims (1)

[Claims] 1. General formula "In the formula, R ¹ and R ² are the same or different,
Indicates a hydrogen atom or an alkyl group. Furthermore, R ¹ and R ² may form a heterocyclic group together with the nitrogen atom to which they are bonded. A is an alkenylene group, R ³ is a hydrogen atom or an alkyl group, R ⁴ is an aryl group which may have a substituent, p is 1, 2 or 3, X is oxygen or sulfur atom, Y is sulfur atom, q is 2,
3 or 4, and Z represents an alkylene group, respectively. ” Amine derivatives and salts thereof.