[Glucuronyl paclitaxel (Taxol) derivatives as tumor activated prodrugs]

Three glucuronyl prodrugs of paclitaxel have been synthesized in order to be activated by the B-glucuronidase present within the necrotic areas of tumors. As three compartments containing prodrugs, they include a specifier, a self immolative spacer and the drug. In vitro testing clearly indicates that the two former prodrugs are stable and are more or less detoxified. As expected, in the presence of E. coli B-glucuronidase, the glycosidic linkage is hydrolyzed with a rate depending on the nature of the spacer but, once this hydrolysis has occurred, the self immolative spacer is soon eliminated leading to the liberation of the paclitaxel.