GB997176A - Anthranilic acid derivatives and process for their manufacture - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0997176/C2/1> wherein R1 is an amino group di-substituted by aliphatic hydrocarbon groups which may be interrupted by an oxygen, nitrogen or sulphur atom and/or may be substituted by a hydroxyl group, Ph represents a phenyl group, optionally bearing lower alkyl, hydroxy, acyloxy, lower alkoxy, methylenedioxy, nitro, amino, mono- or di-lower alkylamino, halogen or trifluoromethyl substituents, R1 represents hydrogen or a lower alkyl or acyl group and R represents hydrogen or a lower alkyl, lower alkoxy or trifluoromethyl group or a halogen atom (the word "lower" indicating a group of up to 7 carbon atoms), together with the corresponding salts, carboxylic esters and amides, and the compound 5-dimethylsulphamyl-2 -anilinobenzoic acid chloride. The acids, esters, anides and salts are made by (a) reacting a corresponding 2-halo-5-sulphamoyl benzoic acid or its ester or amide with an amine of the formula Ph.NH.R1 or (b) reacting a 2-anilino - 5 - sulphamoyl - benzoyl halide with water, an alcohol or a salt thereof, ammonia, or an amine; if desired, converting the resulting compound into a salt or converting a resulting salt into the free compound. Preferably, the substituents on the amino group R1 may be alkyl, e.g. methyl or ethyl, alkenyl, e.g. allyl or methallyl, hydroxyalkyl, e.g. hydroxyethyl or may combine to form an alkylene chain such as butylene, pentylene, hexylene or heptylene, which may be interrupted by hetero atoms to give corresponding oxa-, aza- or thia-alkylene chains. When the product is an ester, the esterifying group is suitably derived from an alkanol, cycloalknaol or a benzyl alcohol the phenyl radical of which may bear substituents as indicated above for the group Ph. When the product is a carboxylic amide, the amide nitrogen action may be mono- or di-substituted, e.g. by alkyl groups or may form part of a pyrrolidine, piperidine, piperazine, morpholine or thiamorpholine ring. Salts of the products include alkali and alkaline-earth metal salts of the acids and acid addition salts of those products which are basic with inorganic and organic acids, e.g. carboxylic and sulphonic acids, including inter alia p-aminosalicylic acid, methionine, tryptophan, lysine or arginine. 1 - Phenyl - 6 - dimethylsulphamyl - 2 - H - 3,1-benzoxazinone-(4) is made by condensing 5-dimethylsulphamoy 1-2-anilino-benzoic acid with formalin. 5 - Dimethylsulphamyl - 2,4 - dichlorobenzoic acid is made by treating 2,4-dichlorobenzoic acid-5 -sulphonyl chloride with dimethylamine. 5 - Dimethylsulphamyl - 2 - aniline - benzoic acid chloride is made by the action of thionyl chloride on the free acid. Pharmaceutical and veterinary preparations having anti-inflammatory, anti-pyretic, analgesic and anti-allergic properties comprise the above acids, esters or amides and their physiologically tolerable salts in admixture or conjunction with a pharmaceutically acceptable carrier. The preparations may take forms suitable for enteral, parenteral or local administration such as tablets, dragees, ointments, creams, solutions, suspensions, emulsions, or for veterinary use, animal feedstuff additives. The salts may be metal, ammonium or amine salts of the free acids, or addition salts with inorganic or organic acids, including ascorbic, salicylic and p-aminosalicylic acids, and methionine, tryptophan, lysine and arginine.