Anthranilic acid derivatives and methods for producing same

摘要

The invention comprises compounds of the formula (wherein "lower alkyl" is a group containing not more than four carbon atoms) and salts thereof, their preparation by (a) condensing a benzoic acid derivative of the formula with a compound of the formula (wherein M is a hydrogen or metal atom, and one of Y and Z is an amino group and the other is a halogen atom), optionally followed by conversion to the free acid or a salt, or (b) hydrolysing a compound of the formula (wherein R is a carboxyl group or a group hydrolysable to a carboxyl group), optionally followed by conversion to the free acid or a salt, and pharmaceutical preparations containing a compound of the invention and a carrier or diluent. 2-Methyl-3-ethylaniline is prepared by reacting 2-iodo-6-nitrotoluene with ethyl iodide in the presence of metallic sodium, and reducing the resulting 2-nitro-6-ethyltoluene with iron in methanol containing hydrochloric acid. N-(2,3-Dimethylphenyl)-benzimidoyl chloride is prepared by heating 21,31-dimethyl-benzanilide with phosphorus pentachloride, and is condensed with methyl salicylate in the presence of sodium ethoxide to yield a crude imido-ester which is heated in a nitrogen atmosphere to yield methyl N-(2,3-dimethylphenyl)-N-benzoylanthranilate. N-Pivalyl-2,3-dimethylaniline is prepared by treating 2,3-dimethylaniline with pivalyl chloride in the presence of pyridine, and is warmed with thionyl chloride to yield N-(2,3-dimethylphenyl)-pivalimidoyl chloride. The latter is condensed with the sodium salt of methyl salicylate, and the resulting pivalimidoic acid ester is heated to yield methyl-N-pivalyl- N-(2,3-dimethylphenyl)- anthranilate, which is hydrolysed to the free acid. o-Cyanophenyl N-(2,3-dimethylphenyl)-benzimidoate is prepared by adding o-cyanophenol to a suspension of sodium hydride in diethylene glycol dimethyl ether, followed by N-(2,3-dimethylphenyl)-benzimidoyl chloride, the mixture being then heated. On heating at 270 DEG C. it affords N-benzoyl-2-cyano-21,31-dimethyldiphenyl-amine, which is hydrolysed by 50% sulphuric acid to the diamide. The compounds of the invention mitigate the symptoms of rheumatic, arthritic and other inflammatory conditions, and may be administered orally or parenterally in the form of pharmaceutical preparations (e.g. tablets, capsules, powders and aqueous and non-aqueous suspensions and solutions) containing them in association with one or more solid or liquid carriers or diluents.