Prodrugs: Strategic Deployment, Metabolic Considerations, and Chemical Design Principles

Abstract

This chapter offers a review of the historical and present‐day design and development of prodrugs. Several case studies are presented to further illustrate the principles being discussed.

Hypoxia Activated Prodrugs of a 9-Aza-anthrapyrazole Derivative That Has Promising Anticancer Activity

“…18 One approach to achieve selective targeting is to mask the chemotherapeutic agent as a prodrug that becomes unmasked at the cancer site. 19 This strategy has been described previously by Cerecetto et al, Lee et al,and Nishida et al 11,20,21 relative to the analogous anthracene system. Herein, we describe the synthesis of 9-aza-anthrapyrazole N-oxide analogues as "bioreductive-dependent agents and as potential hypoxiaselective cytotoxins for cancer therapy".…”

“…One approach to achieve selective targeting is to mask the chemotherapeutic agent as a prodrug that becomes unmasked at the cancer site . This strategy has been described previously by Cerecetto et al, Lee et al, and Nishida et al ,, relative to the analogous anthracene system.…”