Two New Water Soluble Platinum Complexes — CL 286, 558 and CL 287, 110

Several second generation platinum complexes having diamino-cyclohexane or 1,1-bis(aminomethyl)cyclohexane as the stable amine ligand have entered clinical trials. These complexes are (1,2-diaminocyclohexane)malonatoplatinum, aqua[1,1-bis(amino-methyl)cyclohexane]sulfatoplatinum (Spiroplatin), (4-carboxyphthalato)-(1,2-diaminocyclohexane)platinum, and (1,2-diaminocyclohexane)-(isocitrato)platinum (PHIC). Although these compounds exhibited excellent antitumor activity and lack of cross-resistance with DDP, none of them appear to have any future for further clinical evaluation. The major difficulties encountered to date are insufficient water solubility, excessive host toxicity, inadequate purity and lack of acceptable formulation. In order to improve on these drawbacks, we have used a malonate derivative for the carboxylate ligand and incorporated oxygen into the amine ligand and/or the carboxylate ligand, and a few hundred platinum complexes have been synthesized.