JPH05262718A - 5-substituted amino-2-phenoxysulfonamide compound - Google Patents

Abstract

PURPOSE:To obtain a new substituted-amino-2-phenoxysulfonanilide compound and its salt having strongly anti-inflammatory action, antipyretic action, analgesic action and antiallergic action. CONSTITUTION:A substituted-amino-2-phenoxysulfonanilide compound of formula I (R<1> is 1-5C alkyl; R<2> is 1-7C alkyl, allyl or benzyl; X<1> and X<2> are H or halogen; Y is O, S or sulfinyl; (m) is 0-4 integer) and its salt such as N-(5- methyloxalylamino-4-nitro-2-phenoxyphenyl)methanesulfonamide. The compound of formula I, for example, a compound of formula Ia wherein Y is O or S in the formula I is obtained by reacting amino group of 2-fluoro-5-nitroaniline with a sulfonic acid compound of formula II to give a compound of formula III, reacting this compound with a compound of formula IV to give a compound of formula V, then successively converting this compound to a compound of formula VI and a compound of formula VIII and finally nitrating this compound.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a 5-substituted amino-2-phenoxysulfonanilide compound having anti-inflammatory action, antipyretic action, analgesic action and antiallergic action and salts thereof.

[0002]

2. Description of the Related Art A 2-phenoxysulfoneanilide compound having an amino group at the 5-position is disclosed in US Pat.
The compounds described in 56,859 are known, but their anti-inflammatory action was not strong.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a compound having a strong anti-inflammatory action, antipyretic action, analgesic action and antiallergic action.

[0004]

Means for Solving the Problems As a result of intensive studies aimed at solving the above-mentioned problems, the present inventors have shown the following 5-
The inventors have found that a substituted amino-2-phenoxysulfoneanilide compound can achieve the object, and completed the present invention.
The present invention has the formula (I)

[0005]

(Wherein R ¹ represents an alkyl group having 1 to 5 carbon atoms, R ² represents an alkyl group having 1 to 7 carbon atoms, an allyl group or a benzyl group, and X ¹ and X ² Are the same or different and each represents a hydrogen atom or a halogen atom, Y represents an oxygen atom, a sulfur atom or a sulfinyl group, and m represents an integer of 0 to 4). Anilide compounds and salts thereof.

In the present invention, R ¹ has 1 to 5 carbon atoms.
Individual alkyl groups include, for example, methyl group, ethyl group, n-
A propyl group, an n-butyl group, and an n-pentyl group. Further, the alkyl group having 1 to 7 carbon atoms of R ² is, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a t-butyl group, an n-
Examples include a pentyl group, a 2-methylbutyl group, a 3-methylbutyl group, an n-hexyl group, a 3-methylpentyl group, a 4-methylpentyl group, a 2-ethylbutyl group and an n-heptyl group. The halogen atom of X ¹ and X ² is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. The salt of the compound of the formula (I) is an alkali metal salt with sodium, potassium, etc., an alkaline earth metal salt with calcium, magnesium, etc., an ammonium salt and a salt with an organic base such as ethanolamine, pyridine, lysine, arginine, etc. Is.

The compound of formula (I) of the present invention can be produced, for example, by the method shown below. (1) In the formula (I), the compound in which Y is an oxygen atom or a sulfur atom can be obtained as follows using 2-fluoro-5-nitroaniline as a starting material.

[0009]

(In the reaction formula, R ¹ , R ² , X ¹ , X ² and m
Has the same meaning as above, and Y'represents an oxygen atom or a sulfur atom. ) (A) That is, first, the amino group of 2-fluoro-5-nitroaniline and the formula (II) R ¹ —SO ₃ H (wherein R ¹
Is as defined above. The compound of formula (III) can be obtained by reacting a sulfonic acid compound represented by (4) or a reactive derivative thereof (for example, an acid halide, an acid anhydride, etc.). This reaction can be carried out by a usual method for sulfonylating an amino group. When the sulfonic acid compound of formula (II) is used, it is preferably carried out in the presence of a condensing agent such as N, N'-dicyclohexylcarbodiimide. When the reactive derivative is used, it is preferably carried out in the presence of a base, and examples of the base include lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like. Inorganic base or triethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.
3.0] -5-nonene, 1,8-diazabicyclo [5.
4.0] -7-undecene, 4-methylmorpholine, 1
Examples include organic bases such as -methylpiperidine, pyridine, and N, N-dimethylaminopyridine. This reaction is usually carried out in a solvent, and as the solvent, dichloromethane, chloroform, ethyl acetate, dioxane, tetrahydrofuran, ethyl ether, n-propyl ether, isopropyl ether, benzene, toluene, xylene, acetone, acetonitrile, water, pyridine, Examples include N, N-dimethylformamide, dimethyl sulfoxide, and the like.

(B) The compound of formula (III) and the compound of formula (I
V) (wherein X ¹ , X ² and Y ′ are as defined above) are condensed in the presence of a base to give a compound of formula (V). Examples of the base in this reaction include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, and alkali metals such as sodium hydrogen carbonate and potassium hydrogen carbonate. Alkali metal hydrides such as metal hydrogen carbonate, sodium hydride and potassium hydride, inorganic bases such as metal sodium and sodium amide, or triethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0]- 5-nonene, 1,8-diazabicyclo [5.4.0] -7-undecene, pyridine, N,
Examples thereof include organic bases such as N-dimethylaminopyridine. This reaction is carried out without solvent or in dioxane, tetrahydrofuran, ethyl ether, n-propyroether, isopropylate, petroleum ether, n-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, N, N-dimethyl. It is possible to arbitrarily select a solvent such as formamide, dimethyl sulfoxide, dichloromethane or chloroform. Furthermore, in this reaction, potassium iodide, tris [2- (2-methoxyethoxy) ethyl] amine, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide. The reaction can also be accelerated by adding a quaternary ammonium salt such as tricaptylmethylammonium chloride or a crown ether such as 18-crown-6 ether.

(C) Next, the nitro group of the compound of formula (V) is reduced to give an amino compound [compound of formula (VI)]. The reduction may be a usual reduction method of reducing a nitro group to an amino group, for example, palladium-carbon, Raney nickel,
Examples thereof include catalytic reduction using platinum or the like as a catalyst, reduction using iron or tin, reduction using sodium sulfide-ammonium chloride, reduction using sodium borohydride, lithium aluminum hydride and the like. The solvent used in the reaction may be arbitrarily selected depending on the reduction method,
Generally, alcohols such as methanol, ethanol, n-propanol and isopropanol, water, acetic acid, ethyl acetate, dioxane, tetrahydrofuran, acetonitrile and the like can be mentioned.

(D) Subsequently, the amino group of the compound of formula (VI) obtained above is converted to the formula (VII) R ² —OCO— (CH ₂ )
A compound represented by the formula (VIII) can be obtained by acylation with a compound represented by m-CO ₂ H (wherein R ² and m are synonymous with the above) or an acid halide thereof. .. When the carboxylic acid represented by the formula (VII) is used, it is used in the presence of a condensing agent such as N, N'-dicyclohexylcarbodiimide, 1,1'-carbodiimidazole, methanesulfonyl chloride, ethyl chloroformate. It is preferable to carry out. When an acid halide is used, it is preferably carried out in the presence of a base, and examples of the base include lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate. Inorganic base or triethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0] -5-nonene, 1,8-diazabicyclo [5.4.0] -7-undecene, 4-methylmorpholine, Examples thereof include organic bases such as 1-methylpiperidine, pyridine, and N, N-dimethylaminopyridine. This reaction is usually carried out in a solvent, but as the solvent, dichloromethane, chloroform, ethyl acetate, dioxane, tetrahydrofuran, ethyl ether, n-propyl ether, isopropyl ether, benzene, toluene, xylene, chlorobenzene, acetone, acetonitrile,
Water, pyridine, N, N-dimethylformamide, dimethylsulfoxide and the like can be mentioned.

(E) Finally, the compound of the formula (VIII) can be obtained by nitrating the compound of the formula (VIII) with a nitrating agent such as nitric acid or a nitrate. .. Examples of nitrates used in the nitration reaction include sodium nitrate, potassium nitrate, iron nitrate, urea nitrate and the like. The solvent used in this reaction is preferably arbitrarily selected according to the nitrating agent, acetic acid, acetic anhydride,
Trifluoroacetic acid, sulfuric acid, dichloromethane, chloroform, benzene, dioxane, methanol, ethanol,
Examples include n-propanol and isopropanol.

(2) m in the formula (Ia) of the above (1)
Is 1 and R ² is a group other than a methyl group,
It can also be obtained from the compound of formula (IX) as follows.

[0016]

(In the reaction formula, R ¹ , X ¹ , X ² and Y'have the same meanings as described above, and R ³ represents R ² other than a methyl group.) (A) First, the formula (IX The compound of formula (X) can be obtained by hydrolyzing the methyl ester moiety of the compound of). The hydrolysis in this reaction can be carried out by a usual ester hydrolysis method under acidic conditions or basic conditions, but it is preferably carried out under basic conditions, and examples of the base include lithium hydroxide, sodium hydroxide and hydroxide. Examples thereof include potassium, lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, lithium carbonate, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, potassium t-butoxide and the like. Examples of the solvent used in this reaction include water, methanol, ethanol, n-propanol, isopropanol, tetrahydrofuran, dioxane, benzene, toluene, xylene, chlorobenzene, N, N-dimethylformamide, dimethylsulfoxide, and the like. It is preferable to select appropriately according to the conditions.

(B) Then, a carboxyl group of the formula (X) is reacted with a compound represented by the formula R ³ --OH (wherein R ³ has the same meaning as described above) to give a compound of the formula (XI). Can be obtained. This reaction is preferably carried out in the presence of an acid catalyst, and examples of the acid catalyst include inorganic acids such as hydrogen chloride, sulfuric acid and perchloric acid, and organic acids such as paratoluenesulfonic acid and camphorsulfonic acid. The solvent used in this reaction is acetone, acetonitrile, tetrahydrofuran, dioxane, benzene, toluene, xylene, chlorobenzene, N, N-dimethylformamide,
Dimethyl sulfoxide and the like can be mentioned, but it is preferable to select appropriately depending on the acid catalyst.

(C) Finally, by nitrating the compound of formula (XI) in the same manner as in the above method (1) (e),
The compound of the present invention [compound of formula (Ib)] can be obtained.

(3) In the formula (Ia) of the above (1), m
The compound wherein is an integer of 2 to 4 can also be obtained from the compound of formula (VI) as follows.

[0021]

(In the reaction formula, R ¹ , R ² , X ¹ , X ² and Y'have the same meanings as described above, and n represents an integer of 2 to 4,
Z represents a leaving group such as a halogen atom or a methanesulfonyloxy group. ) (A) That is, first, a compound of formula (VI) can be reacted with a carboxylic acid anhydride [compound of formula (XII)] to obtain a compound of formula (XIII). This reaction is usually carried out in a solvent, which may be dichloromethane, chloroform, ethyl acetate, dioxane, tetrahydrofuran, ethyl ether, n-propyl ether,
Examples include isopropyl ether, benzene, toluene, xylene, chlorobenzene, acetone, acetonitrile and the like.

(B) Next, by reacting the carboxyl group of the formula (XIII) with a compound represented by the formula R ² -Z (wherein R ² and Z have the same meanings as described above), a compound of the formula ( XIV) compounds can be obtained. This reaction is preferably carried out in the presence of a base, and examples of the base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, and carbonates. Alkali metal hydrogen carbonates such as sodium hydrogen and potassium hydrogen carbonate, alkali metal hydrides such as sodium hydride and potassium hydride, inorganic bases such as metal sodium and sodium amide, or triethylamine, tri-n-butylamine,
1,5-diazabicyclo [4.3.0] -5-nonene,
Examples thereof include organic bases such as 1,8-diazabicyclo [5.4.0] -7-undecene, pyridine, and N, N-dimethylaminopyridine. This reaction is solvent-free or dioxane, tetrahydrofuran, ethyl ether,
Petroleum ether, n-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine,
A solvent such as N, N-dimethylformamide, dimethylsulfoxide, dichloromethane or chloroform can be arbitrarily selected and used. Furthermore, in this reaction,
Potassium iodide, tris [2- (2-methoxyethoxy) ethyl] amine, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide,
Quaternary ammonium salts such as benzyltriethylammonium chloride, benzyltriethylammonium bromide, tricaptylmethylammonium chloride, 18-
The reaction can also be accelerated by adding a crown ether such as crown-6 ether.

(C) Finally, by nitrating the compound of formula (XIV) in the same manner as in the above method (1) (e),
The compound of the present invention [compound of formula (1c)] can be obtained.

(4) The compound of the present invention in which Y in formula (I) is a sulfinyl group can be obtained by oxidizing the sulfenyl group of the compound in which Y is a sulfur atom in formula (I). The oxidation in this reaction is a usual oxidation reaction that oxidizes a sulfide to a sulfoxide, and includes, for example, hydrogen peroxide, t-butyl hydroperoxide, metachloroperbenzoic acid, peracetic acid, sodium metaperiodate, and bromic acid. Examples thereof include a method using sodium, sodium hypochlorite, periodate benzene and the like.
The solvent used in this reaction is methanol, ethanol, n
-Propanol, isopropanol, dichloromethane,
Chloroform, tetrahydrofuran, dioxane, acetone, acetonitrile, ethyl acetate, benzene, toluene, xylene, chlorobenzene, N, N-dimethylformamide, water and the like can be mentioned, but it is preferably selected appropriately depending on the conditions of the oxidation reaction.

The compounds of the present invention can be administered orally or parenterally in conventional dosage forms. These include, for example, tablets, powders, granules, powders, capsules, solutions, emulsions, suspensions, injections and the like, all of which can be produced by a usual method. When used as an anti-inflammatory agent, antipyretic agent, analgesic agent, and antiallergic agent for humans, the dose is usually 5 to 1000 mg per day, although it varies depending on age, body weight, symptoms, administration route, number of administrations, and the like.

[0027]

INDUSTRIAL APPLICABILITY The compound of the present invention exhibits anti-inflammatory action, antipyretic action, analgesic action and anti-allergic action, and since it has few side effects such as gastrointestinal disorders, it is useful as an anti-inflammatory agent, antipyretic agent, analgesic agent and antiallergic agent. Is.

[0028]

EXAMPLES Next, the present invention will be described in more detail with reference to examples. Example 1 (1) To a 334 ml solution of pyridine containing 52.1 g of 2-fluoro-5-nitroaniline, 42.1 g of methanesulfonyl chloride was added under ice cooling, and the mixture was stirred at room temperature for 7 hours. Water was added to the reaction solution, the precipitate was filtered, and the crude crystals were recrystallized from ethanol to give pale yellow needle crystals of N- (2-fluoro-5-nitrophenyl) methanesulfonamide 56.
9 g were obtained. m. p. 128-129 ° C (2) Phenol 73.5g and sodium hydroxide 3
In 250 ml aqueous solution containing 1.2 g, N- (2-fluoro-5-nitrophenyl) methanesulfonamide 50.
After adding 0 g and refluxing for 5 hours, the reaction solution was cooled with ice and stirred,
50 ml of 36% hydrochloric acid and 200 ml of ethanol were sequentially added. The precipitate was collected by filtration, washed with water and benzene in that order, and then air-dried overnight to obtain 52.2 g of N- (5-nitro-2-phenoxyphenyl) methanesulfonamide as light brown crystals. m. p. 111.5-113 ° C. (3) N- (5-nitro-2-phenoxyphenyl) methanesulfonamide 44.8 g ammonium chloride 2.
A 50 ml aqueous solution containing 6 g was added, and 40.7 g of iron powder was gradually added with heating and stirring at 80 ° C., followed by heating and stirring for 2 hours. The reaction product was returned to room temperature, 250 ml of ethyl acetate was added, and the insoluble material was filtered off. The filtrate was washed with water and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off,
The residue was recrystallized from ethanol to give N as pale brown prism crystals.
33.2 g of-(5-amino-2-phenoxyphenyl) methanesulfonamide was obtained. m. p. 112-113.5 ° C. (4) N- (5-amino-2-phenoxyphenyl) methanesulfonamide 1.5 g and pyridine 0.45 g
0.69 g of methyloxalyl chloride was added to a 6 ml solution of dichloromethane containing the above under cooling at -78 ° C, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction solution, the mixture was extracted with dichloromethane, and the organic layer was washed with water, 3N hydrochloric acid and saturated brine in that order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to give colorless needle crystals of N.
1.5 g of-(5-methyloxalylamino-2-phenoxyphenyl) methanesulfonamide was obtained. m. p. 158 to 159.5 ° C. (5) A solution of 1.4 g of N- (5-methyloxalylamino-2-phenoxyphenyl) methanesulfonamide in 8 ml of acetic acid was stirred at 95 ° C. under heating with stirring to obtain 60% nitric acid.
42 g was added and stirred for 10 minutes. The reaction solution was returned to room temperature, water was added, and the precipitated crystals were collected by filtration and recrystallized from ethanol to give yellow needle crystals of N- (5-methyloxalylamino-4-nitro-2-phenoxyphenyl) methanesulfone. 1.2 g of amide was obtained. m. p. 180.5-182.5 ° C

Example 2 (1) 0.34 g of n-propanol was added to a solution of 6 ml of dichloromethane containing 0.72 g of oxalyl chloride under ice cooling.
And 0.45 g of pyridine were added and stirred for 10 minutes.
The reaction solution was cooled to −78 ° C. to obtain the N-obtained in Example 1 (3).
A solution of 6 g of dichloromethane containing 1.5 g of (5-amino-2-phenoxyphenyl) methanesulfonamide and 0.45 g of pyridine was added, and the mixture was stirred at room temperature for 1 hour.
Water was added to the reaction solution, the mixture was extracted with dichloromethane, and the organic layer was washed with water, 3N hydrochloric acid and saturated brine in that order, and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was recrystallized from ethanol to give colorless crystals of N- [2-phenoxy-5].
1.3 g of-(n-propyloxalylamino) phenyl] methanesulfonamide was obtained. m. p. 132 to 133.5 ° C (2) N- [2-phenoxy-5- (n-propyloxalylamino) phenyl] methanesulfonamide was nitrated in the same manner as in Example 1 (5) to give N-.
[4-Nitro-2-phenoxy-5- (n-propyloxalylamino) phenyl] methanesulfonamide was obtained. m. p. 153.5-155 ° C (ethanol)

Example 3 (1) To 8 ml of a dichloromethane solution containing 1.3 g of adipic acid monomethyl ester, 0.65 g of thionyl chloride was added under ice cooling, stirred for 15 minutes, and then cooled at -78 ° C.
A suspension of 12 ml of dichloromethane containing 1.5 g of N- (5-amino-2-phenoxyphenyl) methanesulfonamide obtained in Example 1 (3) and 1.6 g of pyridine was added, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction solution, the mixture was extracted with dichloromethane, and the organic layer was washed with 3N hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate solution, water, and saturated saline in this order, and dried over anhydrous magnesium sulfate. After distilling off the solvent,
Recrystallized from ethyl acetate-n-hexane to give N- [5- (5
1.7 g of -methoxycarbonylvalerylamino) -2-phenoxyphenyl] methanesulfonamide were obtained. m. p. 127.5-129 ° C. (2) By nitrating N- [5- (5-methoxycarbonylvalerylamino) -2-phenoxyphenyl] methanesulfonamide in the same manner as in Example 1 (5),
N- [5- (5-methoxycarbonylvalerylamino)
-4-Nitro-2-phenoxyphenyl] methanesulfonamide was obtained. m. p. 117.5-118.5 ° C (ethyl acetate-n-
Hexane)

Examples 4 to 16 In Example 1, methanesulfonyl chloride, ethanesulfonyl chloride or n-butanesulfonyl chloride was used as the sulfonyl chloride of Example 1 (1),
As the phenols of Example 1 (2), phenol, 2-
Using fluorophenol or 2,4-difluorophenol, ethyl oxalyl chloride, methoxycarbonylacetyl chloride, 3-methoxycarbonylpropionyl chloride, 3 as the acid chloride of Example 1 (4)
-Ethoxycarbonylpropionyl chloride or 4-
The compounds shown in Table 1 were obtained in the same manner as in Example 1 except that methoxycarbonylbutyryl chloride was used.

[0032]

[Table 1]

Examples 17 to 33 In Example 2, the N- (5-amino-2-phenoxyphenyl) methanesulfonamide obtained in Example 1 (3) as the aniline of Example 2 (1) or the example was used. 1
Using compounds obtained in the same manner as in (1) to (3) (compounds shown in Table 2, ethanol was used as a recrystallization solvent), n-propanol, n-butanol, and n-pen were used as alcohols. The compounds shown in Table 3 were obtained in the same manner as in Example 2 except that tanol, n-hexanol, n-heptanol, isopropanol, isobutanol, 2-methylbutanol, allyl alcohol or benzyl alcohol was used (recrystallization solvent Was used ethanol.).

[0034]

[Table 2]

[0035]

[Table 3]

Example 34 (1) N which is a synthetic intermediate of the compound obtained in Example 8
-(5-methoxycarbonylacetamino-2-phenoxyphenyl) methanesulfonamide 21.0m containing 21.0 g of 2: 1-tetrahydrofuran-ethanol in 167 ml of a solution containing 5.2 g of sodium hydroxide under ice cooling.
1 aqueous solution was added and stirred for 30 minutes. The reaction mixture was concentrated under reduced pressure, 3N hydrochloric acid was added, the precipitate was collected by filtration, and recrystallized from ethanol to give colorless crystals of N- (5-carboxyacetamino-2-phenoxyphenyl) methanesulfonamide 18. 7 g was obtained. m. p. 160-161.5 ° C. (2) N- (5-carboxyacetamino-2-phenoxyphenyl) methanesulfonamide 1.5 g, ethanol 0.57 g and paratoluenesulfonic acid 0.08
An 8 ml toluene solution containing g was refluxed for 1 hour. The reaction solution was returned to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, 5% aqueous sodium hydrogen carbonate solution and saturated brine in this order, and dried over anhydrous magnesium sulfate. After evaporating the solvent, the residue was recrystallized from ethanol to obtain 0.82 g of N- (5-ethoxycarbonylacetamino-2-phenoxyphenyl) methanesulfonamide. m. p. 100 to 101.5 ° C. (3) N- (5-ethoxycarbonylacetamino-2)
N- (5-) was obtained by nitrating the -phenoxyphenyl) methanesulfonamide in the same manner as in Example 1 (5).
Ethoxycarbonylacetamino-4-nitro-2-phenoxyphenyl) methanesulfonamide was obtained. m. p. 144-146 ° C (ethanol)

Example 35 N- [4-Nitro-2-phenoxy-5 was prepared in the same manner as in Example 34 except that n-propanol was used in place of ethanol in Example 34 (2). −
(N-Propoxycarbonylacetamino) phenyl]
Methanesulfonamide was obtained. m. p. 125-127 ° C (ethanol)

Examples 36 and 37 In Example 1, thiophenol was used in place of the phenol of Example 1 (2), and n-pentyloxalyl chloride or ethoxycarbonylacetyl chloride was used as the acid chloride of Example 1 (4). N- [4-Nitro-5- (n-pentyloxalylamino) -2-phenylthiophenyl] methanesulfonamide (mp 139.5-140 ° C.) in the same manner as in Example 1 except for the use. And N- (5-ethoxycarbonylacetylamino-4-
Nitro-2-phenylthiophenyl) methanesulfonamide (mp 134 to 135.5 ° C.) was obtained (ethanol was used as the recrystallization solvent).

Example 38 8 ml of N, N-dimethylformamide containing 0.53 g of N- [4-nitro-5- (n-pentyloxalylamino) -2-phenylthiophenyl] methanesulfonamide obtained in Example 36. Under ice-cooling, 0.28 g of metachloroperbenzoic acid was added to the solution and stirred for 20 minutes. The reaction solution was returned to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated sodium hydrogencarbonate and saturated brine in this order, the solvent was evaporated, and the residue was recrystallized from ethanol to give N-.
[4-nitro-5- (n-pentyloxalylamino)
0.02 g of 2-phenylsulfinylphenyl] methanesulfonamide was obtained. m. p. 147.5-149 ° C

Test Example 1 Carrageenin paw edema test The carrageenin paw edema test was performed by the method of Winter et al.
c. Soc. Exp. Biol. Med. , 111
Vol. 544 (1962)]. Using Wistar rats (6 per group), a sample [inventive compound af and a control drug (indomethacin)] suspended in a 5% aqueous solution of gum arabic was used in an amount of 1 ml per 100 g body weight.
Orally. One hour later, 0.1% of carrageenin was subcutaneously administered to the foot pad of the left limb. Carrageenin administration 3
After a lapse of time, the paw volume was measured, and the edema inhibition rate was determined to examine the anti-inflammatory effect. The dose of the sample is 1 mg / kg.
And The results are shown in Table 4.

[0041]

[Table 4]

[0042]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Internal reference number FI Technical indication location C07C 317/34 7419-4H 323/37 7419-4H (72) Inventor Mariko Kashiwa Takada Toshima-ku, Tokyo 3-24-1 Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuo Hatayama 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd.

Claims (1)

[Claims] 1. A formula (In the formula, R ¹ represents an alkyl group having 1 to 5 carbon atoms, R ² represents an alkyl group having 1 to 7 carbon atoms, an allyl group or a benzyl group, X ¹ and X ² are the same or Differently, a hydrogen atom or a halogen atom is shown, Y is an oxygen atom, a sulfur atom or a sulfinyl group, and m is 0 to
Indicates an integer of 4. ) A 5-substituted amino-2-phenoxysulfoneanilide compound represented by the formula (4) and salts thereof.