5-amino-2-phenoxysulfonanilide compound

Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing

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C07C21145

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active

054498260

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BRIEF SUMMARY
This application is a 371 of PCT/JP93/00518, filed Apr. 21, 1993.


INDUSTRIAL FIELD

The present invention relates to a 5-amino-2-phenoxysulfonanilide compound having anti-inflammatory, antipyretic, analgesic and antirheumatic actions.


BACKGROUND ART

Various 2-phenoxysulfonanilide compounds have been known in the past and especially the compounds described in the specification of U.S. Pat. No. 4,885,367 are considered to be the structurally close to the compound of the present invention.
However, these compounds described in the above-mentioned specification are insufficiently effective.
An object of the present invention is to provide drugs having excellent anti-inflammatory, antipyretic, analgesic and antirheumatic actions.


DISCLOSURE OF THE INVENTION

As a result of extensive researches for the purpose of solving the above-mentioned problem, the present inventors have found that a 5-amino-2-phenoxysulfonanilide compound has excellently useful anti-inflammatory action, and have accomplished the present invention.
The present invention relates to a 5-amino-2-phenoxysulfonanilide compound represented by Formula (I): ##STR2## and to pharmaceutically acceptable salts thereof.
In the present invention, the salt refers to salts with alkali metals (e.g. sodium and potassium), alkaline earth metals (e.g. calcium and magnesium), ammonia and organic bases (e.g. ethanolamine, lysine and arginine).
The compound of Formula (I) of the present invention can be prepared, for example, by the following preparation steps (a) to (f).
(a) First, 2-fluoro-5-nitroaniline is reacted with methanesulfonic acid or a reactive derivative thereof (e.g. acid halides or acid anhydrides) to give a compound represented by Formula (II): ##STR3##
This reaction wherein the methanesulfonic acid is used is preferably carried out in the presence of a condensing agent such as N,N'-dicyclohexylcarbodiimide. In case where the reactive derivative is used, the reaction is preferably carried out in the presence of a base such as, for example, inorganic bases (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate) or organic bases (e.g. triethylamine, tri-n-butylamine, 1,5-diazabicyclo[4.3.0]-5-nonene, 1,8-diazabicyclo[5.4.0]-7-undecene, 4-methylmorpholine, 1-methylpiperidine, pyridine or N,N-dimethylaminopyridine).
This reaction is usually carried out in the presence of a solvent such as, for example, dichloromethane, chloroform, ethyl acetate, dioxane, tetrahydrofuran, ethyl ether, benzene, toluene, xylene, acetone, acetonitrile, water, pyridine, N,N-dimethylformamide or dimethyl sulfoxide.
(b) Subsequently, a compound of Formula (II) is reacted with phenol in the presence of a base to give a compound represented by Formula (III): ##STR4##
Examples of the base in the reaction are alkali metal hydroxides (e.g. lithium hydroxide, sodium hydroxide and potassium hydroxide), alkali metal carbonates (e.g. sodium carbonate and potassium carbonate), alkali metal bicarbonates (e.g. sodium bicarbonate and potassium bicarbonate), alkali metal hydrides (e.g. sodium hydride and potassium hydride), inorganic bases (e.g. metallic sodium and sodium amide) and organic bases (e.g. triethylamine, tri-n-butylamine, 1,5-diazabicyclo[4.3.0]-5-nonene, 1,8-diazabicyclo[5.4.0]-7-undecene, pyridine and N,N-dimethylaminopyridine).
This reaction may be carried out in the absence or presence of a solvent which is arbitrarily chosen from, for example, dioxane, tetrahydrofuran, ethyl ether, petroleum ether, n-hexane, cyclohexane, benzene, toluene, xylene, pyridine, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform or water. Furthermore, the reaction can be accelerated by adding potassium iodide, tris[2-(2-methoxyethoxy)ethyl]amine, a quaternary ammonium salt (e.g. tetra-n-butylammonium chloride, benzyltriethylammonium chloride and benzyltriethylammonium bromide) or a crown ether (e.g. 18-crown-6 ether).
(c) Then, the nitro group of the compound of Formula (III)

REFERENCES:
patent: 3531552 (1970-09-01), Nelson et al.
patent: 3840597 (1974-10-01), Moore et al.
patent: 3856859 (1974-12-01), Moore
patent: 4866091 (1989-09-01), Matsuo
patent: 4885367 (1989-12-01), Yoshikawa et al.
patent: 5374764 (1994-12-01), Yoshikawa et al.

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