PRODRUGS OF ANTHRACYCLINES FOR CHEMOTHERAPY VIA ENZYME MONOCLONAL-ANTIBODY CONJUGATES

New prodrugs of daunorubicin, 1c, 1e and 2c, including a galactopyrano syl residue linked to the N-3' of the daunosaminyl moiety through subs tituted o- or p-benzyloxycarbonyl groups were synthesized. Their low c ytotoxicity and high stability in plasma fulfil the conditions for ant ibody-directed enzyme prodrug therapy (ADEPT). Enzymatic hydrolysis us ing alpha-D-galactosidase gives rise to daunorubicin by subsequent sel f-elimination of the spacers. However, elimination clearly depends on the aromatic substitution pattern, as demonstrated especially by compa rison with nonsubstituted analogues.