Hydrophilic analogs of (R,R)-diaminocyclohexane dichloroplatinum (DACH) and the influence of relative stereochemistry on antitumor activity

A series of analogs of (R,R)-1,2-diaminocyclohexane dichloroplatinum(II) (DACH) containing stereochemically defined hydroxy groups and appropriate acidic leaving groups were synthesized and tested as antitumor agents. The (1α,2β,3α,4β)-1,4-dihydroxy-2,3-diaminocyclohexane analog showed the highest potency against P388 leukemia in mice. The results indicate that increasing the hydrophilicity of the platinum complex to a certain extent could improve the antitumor activity of the drug. It is also likely that the stereochemical disposition of the substituents on the cyclohexane ring affects the antitumor activity.