Enterohepatic chelating agents—I: General principles and examples

Abstract The principles involved in the design of enterohepatic chelating agents , which facilitate the biliary rather than the renal excretion of toxic metal ions are outlined. The syntheses of some novel chelating agents designed to exhibit such behavior are presented. The basic features exploited in the design of such enterohepatic chelating agents are those which (1) make the chelating agent large enough and sufficiently non-polar to prevent renal filtration, and/or (2) provide it with a structure which allows it to participate in the enterohepatic circulation of the bile acids and their derivatives. The altered electric charge subsequent to metal ion chelation is the major factor acting to prevent the continuing enterohepatic recycling of the metal chelate complex. These agents promote the fecal rather than the urinary excretion of the toxic metals and hence should ameliorate the nephrotoxicity which is a not unusual accompaniment of those chelating agents which facilitate the renal excretion of toxic metals.