A new spacer group derived from arylmalonaldehydes for glucuronylated prodrugs

A new glucuronylated prodrug of doxorubicin, potentially useful for ADEPT or PMT cancer chemotherapy, has been prepared from 4-methyl phenyl malonaldehyde. The enol ether spacer, linked via a carbamate to the 3′-amino group of doxorubicin is rapidly cleaved after β-glucuronidase (E coli) catalyzed hydrolysis at pH 7.2 and 37°C.