GB881510A - Iodine-containing benzoic acid amides and a method of producing same - Google Patents

Abstract

Tetra-, penta-, octa- and deca-iodo-benzoic acid amides of the general formula (I) <FORM:0881510/IV (b)/1> wherein Z is a hydrogen or an iodine atom, an amino group or an acylamino group of not more than 4 carbon atoms. Y is a methylene radical or a polymethylene radical of not more than 6 carbon atoms, a cycloalkylene radical or 5 or 6 carbon atoms, or a phenylene radical, and X is a hydrogen atom, or an alkyl, cycloalkyl, aralkyl or aryl radical, which radical may be substituted with a hydroxyl or lower alkoxy group or, in the case where X is an alkyl radical, it may be substituted with the group <FORM:0881510/IV (b)/2> are prepared by a process in which the principle step is the action of the acid chloride having the formula <FORM:0881510/IV (b)/3> on an alkyl ester of the appropriate amino carboxylic acid or diamino dicarboxylic acid. In Example 2, a solution of 3-iodo-5-amino-benzoic acid in hydrochloric acid is reacted with a solution of NaCl.Cl.I in hydrochloric acid to obtain 3-amino-2,4,5,6-tetraiodobenzoic acid, from which the corresponding acid-chloride is then obtained by treatment with thionyl chloride. In Example 7, methyl-N-beta-hydroxy-ethyl-beta1-aminopropionate is heated with 3-amino-2,4,5,6-tetraiodobenzoyl chloride yielding methyl N - (3 - amino - 2,4,5,6 - tetraiodobenzoyl) - N - beta - hydroxyethyl-beta1-aminopropionate; and the example also describes the preparation of the free acid and the sodium salt. Example 3 describes the preparation of pentaiodo-benzoyl chloride by the action of thionyl chloride on pentaiodobenzoic acid. The latter is obtained by treating diazotized 3-amino-2,4,5,6-tetraiodo-benzoic acid with KI. In Example 9, pentaiodo-benzoyl chloride is heated with methyl alpha-amino-n-butyrate to give methyl N-(pentaiodo-benzoyl)-alpha-amino-n-butyrate. In Example 12, methyl hexamethylene diamine-N,N1-bis-beta-propionate is reacted with 3-amino-2,4,5,6-tetraiodobenzoyl chloride to give the dimethyl ester of hexamethylene-diamino-N,N1-bis-(3-amino - 2,4,5,6 - tetraiodobenzoyl) - N,N1 - bis - beta-propionic acid. These polyiodated benzoic acid amides are effective X-ray contrast agents (Group VI).ALSO:The invention comprises X-ray contrast compositions comprising a tetra-, penta-, octa-and deca-iodo-benzoic acid amide of the general formula <FORM:0881510/VI/1> wherein Z is a hydrogen or an iodine atom, an amino group or an acylamino group of not more than 4 carbon atoms; Y is methylene radical or a polymethylene radical of not more than 6 carbon atoms, a cycloalkylene radical of 5 or 6 carbon atoms, or a phenylene radical; and X is a hydrogen atom, or an alkyl, cyclo-alkyl, aralkyl or aryl radical, which radical may be substituted with an hydroxyl or lower alkoxy group or, in the case where X is an alkyl radical, it may be substituted with the group <FORM:0881510/VI/2> or a non-toxic salt of such a polyiodo-benzoic acid amide, with a non-toxic carrier therefor. Non-toxic salts specified are those of sodium, lithium, diethanolamine, and methyl glucosamine. The free acids as well as the non-toxic salts may be processed to form tablets together with binders such as starch, talc, polyethylene glycol, magnesium stearate, lauryl alcohol sulphonate, or both starch and lactic acid. The polyiodo compound may also be mixed with groundnut oil and lecithine, and filled into gelatine capsules.