Process for the production of DTPA-monoamides of the central carboxylic acid and their use as pharmaceutical agents

A process for the production of a diethylenetriaminepentacarboxylic acid monoamide of formula (I) ##STR26## in which Z, E.sup.1, and E.sup.2 independently of one another, each stand for a hydrogen atom or a saturated or unsaturated, branched or straight-chain C.sub.1 -C.sub.50 alkyl chain, wherein:

• the chain or parts of this chain optionally form a cyclic C.sub.5 -C.sub.8 unit or a bicyclic C.sub.10 -C.sub.14 unit;
• the alkyl chain optionally contains 0 to 10 oxygen or 0 to 2 sulfur atoms, 0 to 3 carbonyl, 0 to 1 thiocarbonyl, 0 to 2 imino, 0 to 2 phenylene, 0 to 1 3-indole, 0 to 1 methyl-imidazol-4-yl, 0 to 3 N--R.sup.3 groups or combinations thereof;
• and
• the alkyl chain is further optionally substituted by 0 to 2 phenyl, 0 to 2 pyridyl, 0 to 5 R.sup.2 O, 0 to 1 HS, 0 to 4 R.sup.2 OOC, 0 to 4R.sup.2 OOC--C.sub.1-4 alkyl, 0 to 1 R.sup.2 (H)N groups or combinations thereof,
• in which optionally present aromatic groups are optionally substituted zero to five times, independently of one another, by fluorine, R.sup.2 O.sub.2 C, R.sup.2 OOC--C.sub.1-4 alkyl, R.sup.2 (H)N, C.sub.1-4 alkyl--NH, R.sup.2 NHOC, R.sup.2 CONH, O.sub.2 N, R.sup.2 O, R.sup.2 groups or combinations thereof,
• R.sup.2 independently of one another, each stand for a hydrogen atom or a straight-chain or branched C.sub.1 -C.sub.4 alkyl radical and
• R.sup.3 independently of one another, each stand for a hydrogen atom or a straight-chain or branched, saturated or unsaturated C.sub.1 -C.sub.30 alkyl radical or
• E.sup.1 and E.sup.2 together with inclusion of the nitrogen atom, are optionally a five- to eight-membered, saturated or unsaturated heterocycle, which optionally contains one to two additional nitrogen, oxygen, sulfur atoms, carbonyl groups or combinations thereof,
• in which the HO, H.sub.2 N, HS and HOOC group(s) optionally contained in E.sup.1 or E.sup.2 are optionally present in protected form and in which free carboxylic acid groups not used for complexing are optionally present as salts of the acid groups with physiologically compatible inorganic or organic cations or as esters or amides of the acid groups, which comprises reacting, in the presence of an organic solvent at a temperature of -10.degree. C. to 50.degree. C. a partially protected diethylenetriaminepentacarboxylic acid compound according to formula II ##STR27## in which R.sup.1 stands for a tert-butyl group or a benzyl group and Z' has the meaning of an optionally protected group Z, in which Z has the above-mentioned meaning, optionally with the addition of an activating reagent, with an amine of formula III ##STR28## in which E.sup.1 and E.sup.2 have the above-mentioned meaning, and then producing the free acid of formula I by selective and mild cleavage of group R.sup.1, as well as the protective groups(s) optionally contained in Z'.