Patent GB-950321-A (GB)
Title: Derivatives of iodophenyl-propionic acids and improvements in and relating to x-ray contrast media
IPC: A61K49/04
Filed: 1960-06-27
Abstract: The invention comprises compounds of the formula: <FORM:0950321/C2/1> in which R is hydrogen or alkyl with 1-6 carbon atoms or cycloalkyl with up to 6 carbon atoms, X is hydrogen or alkyl with 1-6 carbon atoms or a cycloalkyl with up to 6 carbon atoms and R1 and R2 either are each an alkyl radical with 2-6 carbon atoms or, together with the nitrogen atom form a non-aromatic heterocyclic ring of 5-6 members which may contain a further hetero atom, or in the case in which X is an alkyl with 1-6 carbon atoms or a cycloalkyl with up to 6 carbon atoms, may also be methyl, and also the acid addition salts of the specified compounds with physiologically acceptable inorganic and/or organic acids and salts of the specified acids (X = H in the above formula) with likewise physiologically acceptable inorganic and/or organic bases and processes for the preparation thereof wherein (a) a compound of the general formula: <FORM:0950321/C2/2> in which R and X are hydrogen or alkyl with an N-disubstituted formamide of the formula: <FORM:0950321/C2/3> in the presence of an acid reaction promoter such as an acid halide and, if desired, the product is esterified and/or converted into a salt with a non-toxic base or acid; (b) a compound of the formula: <FORM:0950321/C2/4> is reacted with a secondary amine of the formula: <FORM:0950321/C2/5> and if desired the product is esterified and/or converted into a salt; (c) an isocyanate of the general formula: <FORM:0950321/C2/6> is reacted with an N-disubstituted formamide of the formula: <FORM:0950321/C2/7> in the presence of an acid reaction promoter such as hydrogen chloride together with an inert solvent, at elevated temperature, and if desired the resulting product is esterified and/or converted into a salt; (d) a formyl compound of the general formula: <FORM:0950321/C2/8> with a secondary amine of the formula HNR1R2; R1, R2, R and X have the meanings given above and Y being a hydrocarbon radical. Heterocyclic residues specified include piperidino and morpholino. The products are employed in X-ray contrast media (see Division A5).  Examples are furnished.ALSO:X-ray contrast media contain a compound of the formula <FORM:0950321/A5-A6/1> in which R is hydrogen or alkyl with 1-6 carbon atoms or cycloalkyl with to 6 carbon atoms, X is hydrogen or alkyl with 1-6 carbon atoms or a cycloalkyl with up to 6 carbon atoms and R1 and R2 either are each an alkyl group with 2-6 carbon atoms or, together with the nitrogen atom form a non-aromatic heterocyclic ring of 5-6 members which may contain a further hetero atom, or in the case in which X is an alkyl of 1-6 carbon atoms or a cycloalkyl with up to 6 carbon atoms may also be methyl, and also the acid addition salts of the specified compounds with physiologically acceptable inorganic and/or organic acids and salts of the specified acids (X=H in the above formula) with likewise physiologically acceptable inorganic and/or organic bases (see Division C2).  In examples, a  - ethyl - b  - (3 - N - diethylamino - methylene-amino - 2,4,6 - triidophenyl) propionic acid and the corresponding 3-N-piperidino-, 3-N-morpholino, and 3-N-dimethylamino compounds are made up with conventional ingredients into tablets, dragees and capsules.