Design, synthesis, and evaluation of duocarmycin O-amino phenol prodrugs subject to tunable reductive activation

JP Lajiness, WM Robertson, I Dunwiddie…

Index: Lajiness, James P.; Robertson, William M.; Dunwiddie, Irene; Broward, Melinda A.; Vielhauer, George A.; Weir, Scott J.; Boger, Dale L. Journal of Medicinal Chemistry, 2010 , vol. 53, # 21 p. 7731 - 7738

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Citation Number: 23

Abstract

A series of N-acyl O-amino derivatives of seco-CBI-indole2 are reported and examined as prototypical members of a unique class of reductively activated (cleaved) prodrugs of the duocarmycin and CC-1065 family of antitumor agents. These prodrugs were designed to be potentially preferentially activated in hypoxic tumor environments which carry an intrinsically higher concentration of “reducing” nucleophiles (eg, thiols) capable of activating such ...