CHAPTER 10
POLYCYCLIC FUSED
HETEROCYCLES
A number of compounds defy ready assignment to one of the structural
categories that have been used to organize the agents described so far in
this volume. The structures of the agents in this chapter, except for of
the two camptothecins, have little in common with each other beyond
the fact that they do not fit previous categories. The bibliographic details
on several compounds indicate that they were first prepared as much as
three decades ago. They appear here because they were granted a nonpro-
prietary name relatively recently.
1. COMPOUNDS WITH THREE FUSED RINGS
Some of the very earliest antitumor compounds incorporated in their struc-
ture a bis(chloroethylamino) moiety, a group often referred to as a nitrogen
mustard. This quite reactive group kills cells by alkylating DNA, and in
effect inactivating this genetic material by forming covalent cross-links
between the bases. Alkylating activity is, however, not restricted to
DNA as these highly reactive agents attack many other tissues. Drugs
that include this moiety are, as a result, associated with a veritable host
of very serious side effects. The indiscriminate killing action of alkylating
The Organic Chemistry of Drug Synthesis, Volume 7. By Daniel Lednicer
Copyright#2008 John Wiley & Sons, Inc.
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