CHEMICAL AND BIOLOGICAL STUDIES ON A SERIES OF NOVEL (TRANS-(1R,2R)-DIAMINOCYCLOHEXANE)PLATINUM(IV), TRANS-(1S,2S)-DIAMINOCYCLOHEXANE)PLATINUM(IV), AND CIS-1,2-DIAMINOCYCLOHEXANE)PLATINUM(IV) CARBOXYLATE COMPLEXES

A series of novel platinum(IV) complexes of the type DACH-Pt-IV-trans- (Y)(2)-cis-X (where DACH = trans-(1R,2R)-, trans-(1S,2S)-, or cis-1,2- diaminocyclohexane; X = diacetate, oxalate, malonate, methylmalonate, cyclobutanecarboxylate (CBCA), or 1,1-cyclobutanedicarboxylate (CBDCA) ; and Y = acetate or trifluoroacetate) has been synthesized and charac terized by elemental analysis, IR, and Pt-195-NMR spectroscopy. The co mpounds have been tested against cisplatin-sensitive L1210/0 leukemia, cisplatin-resistant L1210/DDP leukemia, and M5076 reticulosarcoma cel l lines in vivo. Most of these analogs displayed reasonable activity a gainst L1210/0 cells (%T/C = 135 to >700). There were no gross differe nces in activity between analogs containing isomers of DACH. Selected compounds were evaluated against L1210/DDP tumor models in which they demonstrated reduced but significant activity compared with activity i n the L1210/0 model. interestingly, complex 20, ans-1R,2R-DACH)-trans- (acetate)(2)-methylmalonate, was highly active against M5076, although it had no activity against-the L1210 lines. The results demonstrate t hat specific combinations of axial and equatorial carboxylate ligands, together with the DACH carrier ligand, can favorably modulate the ant itumor properties of platinum complexes and enhance circumvention of c isplatin resistance.