JP3092827B2 - Alkenamide derivative, antiallergic agent using the alkenamide derivative, alkenoic acid, and method for producing the alkenoic acid - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel alkenamide derivative, an antiallergic agent using the same, an alkenic acid which is an intermediate of the alkenamide derivative, and a method for producing the alkenic acid.

[Prior art]

[0002] In allergic diseases, particularly in type I allergic reactions involving immunoglobulin E, histamine, leukotrienes, etc. can be obtained from certain cells such as mast cells and basophils via an antigen-antibody reaction on the cell membrane. It is known that chemical mediators such as eosinophil chemotactic factor and platelet activating factor are released. Therefore, as an active ingredient of a preventive or therapeutic agent for an allergic disease, a chemical messenger release inhibitor having an action of stabilizing the membrane of such cells has been receiving attention. Such chemical mediator release inhibitors include sodium cromoglycate (Cox, JSG,
(Nature 216: 1328, 1967), which has been confirmed to have an action of suppressing the release of mediators from mast cells.

[0003] For the same purpose, tranilast (Eda et al., Japanese Pharmacological Magazine, 66: 237, 1970), oxatomide (Awouters,
F. et al. Experimentia, 33: 1657, 1977), ketotifen (Martin, U. et al., Arzeim-Forsch. Drug Res., 28:
770, 1978) have been reported.

[Problems to be solved by the invention]

(Problems of the prior art) However, the above-mentioned sodium cromoglycate has a problem that it does not exhibit a medicinal effect by oral administration and has a short duration of action due to tachyphylaxis. In addition, although the above-mentioned tranilast, oxatomide, ketotifen and the like show a medicinal effect by oral administration, problems such as taking a long time until the onset of action and becoming sleepy remain unsolved.

(Object of the Invention) The present invention has been made in view of the above-mentioned problems of the prior art, and an object of the present invention is to obtain a novel alkenamide derivative and an alkenoic acid, and to use the alkenamide derivative to transmit a chemical transfer substance. It has a release inhibiting activity, and to provide an antiallergic agent that does not inhibit the histamine H ₁ receptor. In order to achieve the above object, the present inventors have focused on ω- (3,4-methylenedioxyphenyl) -2-alkenoic acid and conducted intensive research. As a result, ω-3,4-methylenedioxyphenyl was obtained. )-
The present inventors have found that N- (1H-5-tetrazolyl) -2-alkenamide derivatives have excellent antiallergic activity and high safety both in systemic application and topical application, and have completed the present invention.

[0006]

That is, the invention according to claim 1 has the following general formula (I):

Embedded image [Wherein n represents an integer of 0 to 4].

[0007] The invention according to claim 2 is based on claim 1.
Characterized in that it contains the alkeneamide derivative according to the above.
It is an allergic agent.

[0008]

[0009]

Hereinafter, the configuration of the present invention will be described in detail. (Alkenamide derivative and antiallergic agent using the same)
First, the alkenamide derivative according to the present invention and an antiallergic agent using the same will be described. The alkenamide derivative represented by the general formula (I) according to the present invention is a pale yellow crystal that is soluble in ketones such as acetone and methyl ethyl ketone and hardly soluble in alcohols such as ethyl alcohol and propyl alcohol. For the production method, a conventional method of acid amidation reaction can be used. For example, the following general formula (II) [In the formula, m represents an integer of 1 to 4. Represented by] ω-
After converting (3,4-methylenedioxyphenyl) -2-alkenoic acid into its reaction derivative, for example, acid chloride, acid anhydride, mixed acid anhydride, etc., the following formula (III) Can be produced by reacting 5-amino-1H-tetrazole represented by the formula in an inert organic solvent in the presence of a base.

The novel compounds of the present invention include the following. 3- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-propenamide 4- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-butenamide 5- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-pentenamide 6- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-hexenamide 7- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-heptenamide

The alkenamide derivative according to the present invention has excellent antiallergic properties and can be used as an antiallergic agent in various pharmaceuticals. The allergic agent according to the present invention is a pharmaceutical composition which is compatible with the compound of the formula (I) or a salt thereof and comprises one or more pharmaceutically acceptable diluents or activators. Included in that range. These compositions can be administered orally, parenterally, rectally, or topically. The composition of the present invention may be used for administration to humans and animals as tablets, capsules, powders, granules, pills, aqueous or non-aqueous solutions, syrups, suspensions, emulsions,
Oral administration with elixir, etc., aseptically adjusted aqueous or non-aqueous solution, suspension, emulsion, parenteral administration with liposome, etc., rectal administration with suppository or rectal capsule, ointment, cream , Pastes, haptics, gels, aqueous or non-aqueous solutions, suspensions, emulsions, liposomes, aerosols and the like for topical administration to the skin, mucous membranes, nausea, nose, eyes, etc. . In order to achieve the desired effect as an oral preparation, it depends on the patient's age, body weight, individual differences, medical conditions, etc., but it is usually necessary to take 1 to 200 mg as a compound weight once daily for adults, up to 3 times a day. Deemed appropriate. In order to exert the intended effect as a parenteral preparation, intravenous injection, subcutaneous injection, or intramuscular injection of 0.01 to 10 mg per day is also appropriate. 500 mg once or several times a day,
It is considered appropriate to administer to the affected area.

[0013]

(Alkenic Acid and Method for Producing the Alkenic Acid) Next, a method for producing alkenoic acid, which is an intermediate for producing the alkenoic acid derivative according to the present invention, will be described. Compound (IV) [In the formula, m represents an integer of 1 to 4. ] The inert organic solvent or without a solvent with a halogenating agent (e.g., thionyl chloride, phosphoryl chloride, phosphorus oxychloride, phosphorus tribromide, phosphorus pentachloride, etc.) is treated with the resulting acid halide (V) [In the formula, m represents an integer of 1 to 4. ] In the presence of a catalytic reduction catalyst (for example, palladium, platinum, rhodium, ruthenium, nickel, copper chromite, etc.) in an inert organic solvent to give the compound (V
I) [In the formula, m represents an integer of 1 to 4. ) , Followed by Knoevenagel condensation with malonic acid in the presence of a basic catalyst (ammonia, primary amine, secondary amine, pyridine, piperidine, etc.) to give the desired product (II) in good yield.
Can be obtained. In the above method, the inert organic solvent to be used may be any solvent as long as it does not inhibit the reaction, and examples thereof include ether, toluene, xylene, benzene, tetrahydrofuran, dioxane, chloroform, dimethyl sulfoxide, methylene chloride, N,
N-dimethylformamide and the like.

Compound (VI) is replaced with compound (VII)

Embedded image [Wherein m represents an integer of 1 to 4] is epoxidized with a peracid such as perbenzoic acid, and then subjected to an acid treatment to transfer the compound.

In addition, the compound represented by the general formula (II) can be obtained in good yield from the following phosphorane (VIII) and glyoxylate (IX) by utilizing the Wittig reaction.

Embedded image [In the formula, m represents an integer of 1 to 4, and R represents an alkyl group, an allyl group, or a heteroallyl group.]

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below.
Note that the present invention is not limited by this. First, a method for producing alkenoic acid, which is an intermediate for producing the alkeneamide derivative according to the present invention, will be described.

[0018](Production Example 1)  4- (3,4-methylenedioxyphenyl) -2-bute
Acid [m = 1 in the general formula (II)] 2- (3,4-methylenedioxyphenyl) ethanal
[M = 1 in the general formula (IV)] to 5.0 g (30.5 mmol)
Add 10 ml of pyridine and 36.4 g (35 mmol) of malonic acid and complete
After dissolving in water, add 0.3 ml of piperidine and add 3 hours at 90 ° C.
Heated to reflux. The reaction solution was poured into 50 ml of water, and 20 ml of concentrated hydrochloric acid was added.
The precipitated crystals were collected by filtration, washed with water, and dried under reduced pressure.
4.6 g of the desired compound was obtained. Melting point and origin of this substance
The elementary analysis values were as follows. Melting point: 117-119 ° C Elemental analysis: C₁₁H_TenO_Four Calculated: C, 64.07; H, 4.89 Found: C, 64.09; H, 4.89

[0019](Production Example 2)  5- (3,4-methylenedioxyphenyl) -2-pen
Formic acid [m = 2 in the general formula (II)](Production Example 2.1)  3- (3,4-methyldioxyphenyl) -2-propa
Preparation of acid [m = 2 in the general formula (IV)] 3- (3,4-methylenedioxyphenyl) -2-pro
200 g of ethanol and 5% para
Add 300ml of didium carbon and hydrogen at normal pressure for 8 hours at room temperature
Was added. After completion of the reaction, the catalyst was removed by filtration, and the solvent was distilled off under reduced pressure.
And dried to obtain 9.7 g of the desired compound (melting point: 84
~ 85 ° C).

[0020](Production Example 2.2)  3- (3,4-methyldioxyphenyl) -2-propa
Preparation of nal [m = 2 in the general formula (IV)] 3- (3,4-Methylenedi
9.7 g of (oxyphenyl) -2-propanoic acid in benzene 30
and 18.5 ml of thionyl chloride, and react at room temperature for 6 hours.
I let you. The reaction solution was concentrated under reduced pressure, and in the general formula (V), m =
9.4 g of acid chloride 2 was obtained as a pale yellow oil. Continued
Add 40 ml of toluene and 5% palladium-sulfuric acid to the acid chloride of the lever.
Add 1.3g of barium acid and hydrogenate at room temperature for 33 hours
did. After completion of the reaction, the catalyst was removed by filtration, and the filtrate was washed with 5% hydrogencarbonate.
After washing with aqueous thorium solution, add a small amount of ethanol and
After sufficient stirring, the mixture was allowed to stand overnight. Then water,
10% aqueous hydrochloric acid, 5% aqueous sodium carbonate, and then water
Next washing, drying with sodium sulfate, concentration under reduced pressure, distillation under reduced pressure,
The desired compound was obtained (boiling point: 140-145 ° C / 9 mmH
g).

[0021](Production Example 2.3)  5- (3,4 methylenedioxyphenyl) -2-pente
4- (3,4 methylenedioxyphenyl) obtained in 2.2
38 ml of pyridine and 5.8 g of malonic acid in 14.7 g of propanal
And heated at 80 ° C for 1 hour, then at 130 ° C for 6 hours
Refluxed. Less than,Production Example 1Target in a manner similar to
4.2 g of compound were obtained. The melting point and elemental analysis of this substance are
It was as follows. Melting point: 123-127 ° C Elemental analysis C₁₂H₁₂O_Four Calculated: C, 65.45; H, 5.49. Found: C, 65.37; H, 5.50.

[0022](Production Example 3)  6- (3,4-methylenedioxyphenyl) -2-hex
Senoic acid [m = 3 in the general formula (II)] 4- (3,4-methylenedioxyphenyl) -2-butene
Acid 10 g (48.5 mmol)Production Example 2Eyes according to the method
3.9 g of the target compound were obtained. Melting point: 156-159 ° C Elemental analysis: C₁₃H₁₄O_Four Calculated value: C, 66.67; H, 5.98 Actual value: C, 66.63; H, 6.01 Next, a method for producing an alkeneamide derivative according to the present invention will be described.
Will be described.

[0023](Example 1)  3- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-propenamide [n = O in the formula (I)] 3 ml of thionyl chloride was added to 10 ml of benzene,
(3,4-methylenedioxyphenyl) -2-propene
1.0 g of an acid was gradually added, and the mixture was heated under reflux at 80 ° C. for 3 hours. reaction
After the solution was concentrated under reduced pressure, 50 ml of diethyl ether was added, and the solution was
1.1 g of 5-amino-1H-tetrazole, triethyl
0.8 ml of amine was added, and the mixture was stirred at room temperature for 15 hours. Insoluble matter
And the resulting yellow granular crystals are filtered with dimethylsulfoxyl.
Recrystallization from water / water gave 990 mg of the desired compound. Melting point: 259-261 ° C (color decomposition) Elemental analysis: C₁₁H₉O_ThreeN_Five Calculated: C, 50.97; H, 3.50; N, 27.0.
2 Found: C, 50.71; H, 3.52; N, 27.3.
1

[0024](Example 2)  5- (3,4-methylenedioxyphenyl) -N- (1
H-5-tetrazolyl) -2-pentenamide [n = O in the general formula (I)] 5- (3,4-methylenedioxyphenyl) -2-pen
To 5.5 g (25 mmol) of formic acid, 14 ml of triethylamine (0.1
 mol), and add 100 ml of tetrahydrofuran under ice-cooling.
9ml of ethyl chlorocarbamate
Was added slowly and reacted for 1 hour. 5-amino-
8.5 g of 1H-tetrazole was gradually added, and the mixture was stirred for 1 hour under ice cooling.
Stirring was continued. 50 ml of distilled water was added to the reaction solution at room temperature
After that, adjust the pH to 3 with dilute hydrochloric acid, add 500 ml of ethyl acetate, and countercurrent
Partitioned and collected the organic solvent layer. Solvent is distilled off under reduced pressure
And the obtained yellow granular crystals were treated with dimethyl sulfoxide / water.
To give 5.1 g of the desired compound. Melting point: 193-195 ° C (color decomposition) Elemental analysis: C₁₃H₁₃O_ThreeN_Five Calculated: C, 54.36; H, 4.53; N, 24.3.
9 found: C, 54.08; H, 4.54; N, 24.4.
5

Next, the suitability of the alkenamide derivative according to the present invention produced as described above as an antiallergic agent will be described.

(Acute toxicity) An acute toxicity test by oral administration of the alkenamide derivative according to the present invention was carried out. IC
Using male R-mass (body weight 18-22 g, 10 animals per group)
0.5% of the alkenamide derivative shown in Examples 1 and 2
Using a test solution suspended in methylcellulose / physiological saline, each compound was orally administered so as to be 500 mg / Kg. None of the compounds died during the 7-day observation period after administration, and the acute oral toxicity value of the novel compound of the present invention was LD50> 500 mg / Kg.

(Inspection of antiallergic property) Next, the excellent antiallergic action of the alkenamide derivative according to the present invention is shown in vitro and in vivo.
This is clarified from the results of a typical anti-allergic test at o.

(Test Example 1: Mast cell degranulation inhibition test)
The inhibitory effect of the alkenamide derivative according to the present invention on mast cell degranulation reaction based on type allergic reaction was evaluated in vitro using rat peritoneal cells actively sensitized with ditrophenylated keyhole limpet hemocyanin (DNP-KLH). Was tested. Tada and Okumura's method (Journal of Immunology, 106: 1002-1011, 197
SD rats were immunized with DNP-KLH according to 1),
Sensitized peritoneal cells were obtained 3 days after the boost.

After washing the sensitized peritoneal cells, Tyrode's solution (PS-HB) containing 10 μg / ml phosphatidylserine, 10 mM HEPES, and 1 mg / ml bovine serum albumin was added.
T) Suspend in 10 ml, add 100 μl of the test compound solution to 800 μl, pre-incubate at 37 ° C. for 1 minute, and add 100 μl of dinitrophenylated bovine serum albumin (10 μg / ml) as an antigen for 15 minutes.
Allowed to react for minutes. The reaction was stopped by ice-cooling, and separated into a supernatant and a sediment by centrifugation. The amount of histamine in the supernatant (H
s) and the amount of histamine (Hp) in the sediment were quantified by high-performance liquid chromatography after post-labeling after deproteinization with 0.4N perchloric acid, and Hs / (Hs
The histamine release rate was calculated by the formula represented by (+ Hp) × 100.

Further, the histamine release inhibitory rate of the test compound was calculated as (HRt-HRb) / (HRc-HRb) × 100.
Degranulation inhibitory activity (provided that HRt
Is the histamine release rate when the test compound is added, HR
c is the histamine release rate when no test compound is added,
HRb represents the histamine release rate without antigen stimulation).

[0031] to have been produced in Example 1 3- (3,4-methylenedioxyphenyl)-N-(IH-5-tetrazolyl) -2-propenamide (compound of Example 1), actual
For 5- (3,4-methylenedioxyphenyl) -N- (1H-5-tetrazolyl) -2-pentenamide (the compound of Example 2 ) produced in Example 2 , sodium cromoglycate (DSCG) and Table 1 shows the results of tests using tranilast as a control. Table-1 ────────────────────────── Test compound concentration (M) Degranulation inhibition rate (%) ──────── {10 ^-6 10.3 DSCG 10 ^-5 31.5 10 ^-4 62.2} {10 ^-6 -8.1 Tranilast 10 ^-5 17.6 10 ^-4 71.2} {10 ⁻⁶ 9.2 Compound of Example 1 10 ⁻⁵ 36.8 10 ⁻⁴ 76.6} {10 ⁻⁶ 21.2 Compound of Example 2 10 ⁻⁵ 55.0 10 ⁻⁴ 75.7} ───────

As is clear from Table 1 , the alkenamide derivatives of Example 1 and the alkenamide derivatives of Example 2 , which are novel compounds according to the present invention, are known DSCGs.
Alternatively, it showed a stronger degranulation inhibition rate than tranilast, and was found to have an excellent granulocyte membrane stabilizing action.

(Test Example 2: Passive air sac anaphylactic reaction inhibition test) As a test method for measuring the antiallergic action of a drug, a passive air sac anaphylactic reaction inhibition test (Amano et al., The 107th Annual Meeting of the Japan Pharmaceutical Association) Abstracts, p. 559, 1987) are suitable. Weight 180
10 subcutaneously on the shaved back of ± 30 g male SD rats
An air sac was created by injecting ml of air. Into this air sac, 2 ml of anti-DNP-KLH antiserum diluted with physiological saline was injected, and after massage, 5 ml of air was withdrawn. 48
After an hour, 5 ml of a 0.5% methylcellulose solution containing 2 mg of DNP-modified bovine serum albumin was injected into the air pouch to induce an anaphylactic reaction. The effect of the test compound was measured using the inhibitory effects on vascular permeability and free histamine level as indices. Vessel permeability is determined by the method of Watanabe et al. (Jo
urnal of Pharmacological Method, 11: 13-20,
1984). That is, rats were sacrificed 10 minutes after intravenous injection of 10 mg / 0.2 ml of bovine serum albumin (F-BSA) conjugated with fluorescein isothiocyanate as a tracer,
The intracapsular fluid was collected. The amount of F-BSA leaked into the intracapsular fluid was measured, and the percentage calculated based on the amount of intravenously injected F-BSA was used as an index of vascular permeability. Histamine in the collected sac fluid was measured by Von Redlich
(Journal of Analytical Biochemistry, 1)
0: 459-467, 1965). In the case of local administration, the test compound was directly dissolved in the antigen solution, and 5 ml of the test compound was administered at the time of induction. In the case of intravenous administration, the test compound was dissolved in physiological saline and administered 10 minutes before the induction.

The vascular permeability inhibitory action and histamine release inhibitory action of the compound of Example 1 and the compound of Example 2 were compared with those of DSCG and tranilast. The average value (R1) of the group to which the test compound was administered and the average value (R0) of the control group to which no test compound was administered were determined, and (R0-R
1) The inhibition rate (%) of each compound was calculated from the formula of × 100 / R0, and the result was defined as the anti-allergic activity of the test compound. The larger this value is, the higher the antiallergic activity is. Table 2 shows the results when the test compound was locally administered.
Table 3 shows the results of intravenous administration, and Table 4 shows the results of oral administration.

Table 2 Local administration ──────────────────────────────────── Test compound dose Amount Permeability inhibition rate Histamine release (μg / ml) (%) Inhibition rate (%) ─────────────────────────────── {DSCG 10.0 68.3 70.2} ─ Tranilast 300.0 54.1 51.3 ──────────────────────────────────── Example 1 Compound of 10.0 64.7 75.1 { Example 2 Compound of 10.0 70.6 74.9} ───────────────────

Table 3 Intravenous administration ──────────────────────────────────── Test compound dose Inhibition rate of vascular permeability Histamine release (μg / ml) (%) Inhibition rate (%) ────────────────────────────── {DSCG 1.0 54.3 52.2} ── Tranilast 30.0 54.1 51.3 ──────────────────────────────────── Example Compound of 1 3.0 55.1 51.8 { Examples 2 of compound 3.0 64.1 61.3 ─────────────────── ────────────────

Table 4 Oral administration ──────────────────────────────────── Test compound dose Vessel Permeability inhibition rate Histamine release (μg / ml) (%) Inhibition rate (%) ─────────────────────────────── {DSCG 100.0 -2.4 1.5} ── Tranilast 300.0 34.1 41.3 ──────────────────────────────────── Example Compound of 1 50.0 57.1 55.8 { Examples 2 of the compound 50.0 58.3 62.9 ──────────────── ───────────────────

As is apparent from Tables 2, 3 and 4, the alkenamide derivative of Example 1 and the alkenamide derivative of Example 2 , which are novel compounds according to the present invention, are administered topically and intravenously. In each of the methods of oral administration, high vascular permeability inhibitory activity and histamine release inhibitory activity were exhibited, and it was revealed that they had an excellent antiallergic effect. Therefore, it was suggested that the composition containing the compound of the general formula (I) or a salt thereof according to the present invention as an active ingredient is an excellent antiallergic agent.

Hereinafter, the present invention will be described in more detail with reference to Formulation Examples of the novel compound of the present invention, but the present invention is not limited thereto. In addition, the preparations according to the examples also exhibited excellent antiallergic effects as described above.

( Example 3 : tablet) (1) Compound of Example 1 20 mg (2) Lactose 50 mg (3) Corn starch 25 mg (4) Hydroxypropyl cellulose 2 mg (5) Magnesium stearate 1 mg (6) Talc 2 mg １００ 100mg Mix the above (1)-(4) and add water Add and granulate,
It was then dried. After sieving the obtained granules, (5) and (6) were added and mixed, and the mixture was compression-molded to obtain 100 tablets.
mg tablets were prepared.

( Example 4 : Capsules) (1) 10 mg of the compound of Example 2 (2) Lactose 65 mg (3) Corn starch 20 mg (4) Hydroxypropyl cellulose 3 mg (5) Silicic anhydride 1 mg (6) Stearic acid Magnesium 1mg ──────────────────────────────────── 100mg Mix the above ingredients according to the usual method Granules were obtained. This was filled in a capsule to prepare a capsule of 100 mg each.

Example 5 : Injection (1) Compound of Example 1
2.5g (2) Polysorbate 80
150ml (3) Sterile physiological saline
4850 ml The above (1) was dissolved in (2), and (3) heated to 60 ° C. was added thereto, and the mixture was shaken well. Aseptically, the vial contained 0.5 mg of the compound of Example 4 in a vial. And sealed to produce an injection.

( Example 6 : syrup) (1) Compound of Example 2
500mg (2) Methyl cellulose
2g (3) Sucrose
20g (4) Strawberry essence
0.1 ml (5) Methyl paraben
0.1 g (6) distilled water
A total amount of 100 ml The above (1) was mixed with 50 ml of (6), and then (1), (3), (4) and (5) were added and mixed.
(6) was added to make a total volume of 100 ml to obtain a syrup.

( Example 7 : Cream) (1) Compound of Example 1 1 g (2) Cetostearyl alcohol 4 g (3) Liquid paraffin 40 g (4) Lanolin 7 g (5) Stearic acid monoglyceride 2.2 g (6) Polyoxyethylene (20) sorbitan monostearate 2.8 g (7) 1,3-butylene glycol 6.8 g (8) Ethyl paraben 0.2 g (9) Distilled water 36 g １００ 100g (1) (2) (3) (4) (5) and (6) are dissolved by heating, What was kept at 70 ° C. was heated to 70 ° C. (7)
Add to (8) and (9) with stirring. The mixture was homogenized, and the emulsified particles were finely divided and then rapidly cooled with stirring to obtain a cream.

( Example 8 : Pasta agent) (1) 5 g of the compound of Example 2 (2) 15 g of zinc oxide (3) 14 g of starch (4) 16 g of white petrolatum ５０ 50 g A part of (4) was dissolved in a water bath, (1) was added, and then sieved (2). (3) was kneaded, and the remaining (4) was added and kneaded sufficiently to produce a pasta agent with uniform quality.
In the preparations prepared according to Examples 3 to 8 , the active ingredient was stably present over time.

[0046]

As described above, according to the present invention, an alkenamide derivative having excellent antiallergic properties and alkenoic acid as an intermediate thereof can be obtained.

──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Tetsuji Hirao 1050 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa Prefecture Examiner, Shiseido Research Institute, Inc. Seiko Tamura (56) References JP-A-49-35153 (JP, A) . Chem. Soc. PERKIN TRANS. ▲ I ▼ No. 7 (1982) p. 1493-1498 (58) Field surveyed (Int. Cl. ⁷ , DB name) C07D 405/12 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. An alkene amide derivative represented by the following general formula (I). [In the formula, n represents an integer of 0 to 4. ] 2. An antiallergic agent comprising the alkenamide derivative according to claim 1.