GB1310606A - Adamantylcarboxamidophenylacetic acid derivatives their preparation and compositions containing them - Google Patents

Abstract

1310606 2 - (1 - Adamantylcarboxamido)- phenylacetic acids CIBA-GEIGY AG 25 March 1970 [26 March 1969] 14461/70 Heading C2C Novel 2 - (1 - adamantylcarboxamido)- phenylacetic acids of the general formula wherein one of R 1 and R 2 is a hydrogen, fluorine, chlorine or bromine atom or a C 1-4 alkyl, C 1-4 alkoxy or trifluoromethyl group and the other is a hydrogen atom, or both R 1 and R 2 are C 1-4 alkoxy groups, and R 3 and R 4 are each a hydrogen atom or a C 1-4 alkyl group, and, when R 4 is a hydrogen atom in said formula, pharmaceutically acceptable salts thereof with bases are prepared by reaction of a 2-amino-phenylacetic acid of the general formula with an acylating agent containing a 1-adamantyl-carbonyl group and, when in the product R 4 is a hydrogen atom, optional esterification or salification of the product, or, when in the product R 4 is a C 1-4 alkyl group, optional hydrolysis of the product to give the corresponding free acid or a salt thereof, the latter optionally being converted to the free acid. 2 - Amino - phenylacetic acid esters of the second general formula above wherein R 4 is a C 1-4 alkyl group are prepared by esterification of the corresponding 2-nitro-phenylacetic acid and reduction of the resulting 2-nitro-phenylacetic acid ester. Methyl 2-(2-nitro-4-trifluoromethylphenyl)propionate is prepared by reaction of methyl 2-nitro-4-trifluoromethylphenylacetate with methyl iodide in the presence of sodium hydride. Methyl 2-(2-nitro-4-trifluoromethylphenyl)-hexanoate is prepared analogously from 1 - bromo - n - butane. 4 - Methyl - 2 - nitrophenylacetic acid is prepared by reaction of 3- nitro-4-chlorotoluene with diethyl malonate in the presence of sodium, followed by ethanolic potassium hydroxide solution. 5 - Fluoro - 2- nitrophenylacetic acid is prepared by acid hydrolysis of 5-fluoro-2-nitrophenylacetonitrile. Pharmaceutical compositions having antiinflammatory activity comprise, as active ingredient, a 2 - (1 - adamantylcarboxamido)- phenylacetic acid of the first general formula above or, when R 4 is a hydrogen atom in said formula, a pharmaceutically acceptable salt thereof with a base, together with a pharmaceutically acceptable diluent or carrier therefor, and may be administered orally.