Development and evaluation of the improved iron chelating agents EHPG, HBED and their dimethyl esters.

The phenolic EDTA analogues ethylenediamine-N,N'-bis-(2- hydroxyphenylglycine ) ( EHPG ), N,N'-bis(2-hydroxybenzyl)-ethylenediamine diacetic acid ( HBED ), and their respective dimethyl esters ( dimethylEHPG and dimethylHBED ) were studied in hypertransfused rats. Radioiron bound to these compounds was cleared mainly by the liver and excreted in the bile. After a single 40 mg i.m. injection, the percentage of radioiron removed from 59Fe-ferritin-labelled hepatocytes and excreted in the bile was 4% in untreated controls, 24% for desferral , 42% for dimethylEHPG , 58% for EHPG , 63% for HBED , and 80% for dimethylHBED . DimethylHBED combines oral effectiveness with superior chelating ability, selective hepatocellular action, and low apparent toxicity. It may represent a significant advance in the development of new iron chelating drugs.