Enzyme activated self-immolative n-substituted nitrogen mustard prodrugs

Abstract

This invention pertains to certain enzyme (CPG2) activated self-immolative nitrogen mustard prodrugs, which are useful in enzyme prodrug therapy (EPT), such as ADEPT and GDEPT, for the treatment of proliferative conditions, such as cancer, and which have the following formula: wherein: Ris independently Calkyl; Xis independently —I, —Br, or —Cl; Xis independently —I, —Br, or —Cl; the group —N(CHCHX)(CHCHX) is independently attached at the 2-position or at the 4-position; each Ris independently —H or an ester substituent; n is independently an integer from 0 to 4; each R, if present, is independently a phenyl substituent; m is independently an integer from 0 to 4; each R, if present, is independently a mustard substituent; and pharmaceutically acceptable salts, solvates, amides, and esters thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds; such compounds and compositions for use in methods of treatment of the human or animal body by therapy; the use of such compounds and compositions for the manufacture of medicaments for the treatment of proliferative conditions; and the like.