Scientific Publications by FDA Staff

J Pharm Sci 1982 May;71(5):542-51

Synthesis, hydrolytic reactivity, and anticancer evaluation of N- and O-triorganosilylated compounds as new types of potential prodrugs.

Chiu FT, Chang YH, Ozkan G, Zon G, Fichter KC, Phillips LR

N- and O-Triorganosilylated compounds related to various anticancer agents were synthesized for evaluation as potential anticancer prodrugs. 1H-NMR and UV kinetic measurements of hydrolytic desilylation were used to correlate relative rates of structural unmasking with steric bulk about the silicon reaction center. The tert-butyldimethylsilyl ester of chlorambucil and a number of O- triorganosilylated carbamate derivatives of nor-nitrogen mustard showed significant activity against P-388 lymphocytic leukemia in mice.