Patent GB-884623-A (GB)
Title: New triiodophenyl-propionic acids and x-ray contrast media comprising the same
IPC: C07D295/195
Filed: 1959-03-03
Abstract: The invention comprises compounds of the general formula <FORM:0884623/IV (b)/1> in which R is hydrogen, an alkyl radical of 1-6 carbon atoms or a cycloalkyl radical of 3-6 carbon atoms, and non-toxic salts of these compounds with inorganic and organic bases. These compounds may be used in the production of X-ray contrast media, and they may be used either as free acids or as non-toxic salts such as the sodium, lithium, ammonium, calcium, methylglucamine, ethanolamine, diethanolamine, ethylamine, diethylamine, and methylglucosamine salts.  They may be obtained from the corresponding 2,4,6 - triiodo - 3 - amino - propionic acids by reaction with dimethyl formamide in presence of an acidic reaction promoter such as phosphorus oxychloride.  In an example, a -ethyl-b -(3-amino-2,4,6-triiodo-phenyl) -propionic acid is dissolved in dimethylformamide and treated dropwise with phosphorus oxychloride, the reaction mass is treated with acetone, and the hydrochloride of the amidine which separates is dissolved in hot water and treated with caustic soda to form the internal salt of a  - ethyl - b  - (dimethylamino - methyleneamino - 2,4,6 - triiodophenyl) - propionic acid.  The corresponding a -methyl compound is obtained in a similar manner.  Compounds containing other alkyl substituents, e.g. n-propyl or n-butyl, in the a -position of the propionic acid are referred to. In another example, b -(3-amino-2,4,6-triiodophenyl)-propionic acid is dissolved in a mixture of dimethyl formamide and chloroform and treated with phosphorus oxychloride to obtain b -(3-dimethylamino-methylene-amino-2,4,6-triiodophenyl)-propionic acid.ALSO:Compounds of the formula <FORM:0884623/VI/1> in which R is hydrogen, an alkyl radical of 1-6 carbon atoms, or a cycloalkyl radical of 3-6 carbon atoms, and non-toxic salts of these compounds, are used together with a carrier material to form X-ray contrast media.  Salts which may be used include the sodium, lithium, ammonium, calcium, methylglucamine, ethanolamine, ethylamine, and methyl-glucosamine salts.  The media may be prepared in the form of tablets, capsules, or dragees, and may be administered intravenously, perorally, or intraduodenally.  The active substances have low toxicity, and very good capacity for absorption and distribution.  In an example: a -ethyl - b  - (3 - dimethylamino - methylene - amino - 2,4,6 - triiodophenyl) - propionic acid is pasted with maize-starch paste, granulated and dried, then mixed with starch and magnesium stearate, and moulded into tablets.  The corresponding compounds having methyl, n-propyl or n-butyl as substituent in the a -position of the propionic acid may be used.  The granulated product may be formed into dragees by coating with sugar syrup and waxing.  In another example, the calcium salt of b -(3-dimethylamino - methyleneamino - 2,4,6 - triiodophenyl)-propionic acid is mixed with sugar, sodium lauryl sulphonate, sodium carboxymethyl cellulose, and flavouring.  The mixture may be taken with water.  If the active substance is to be filled into gelatine capsules on a machine, it may first be worked up with liquid paraffin to a fluid paste.