CHAPTER 3
3 MONOCYCLIC AROMATIC COMPOUNDS
COMPOUNDS
Free-standing benzene rings have provided the core for a very large number
of biologicallyactive compounds. This ubiquitous unit providesthe rigid flat
skeleton on which to attach functional groups and also manifeststhe electron
density required for recognition at various receptor sites. The ubiquitous
occurrence of aromatic rings in endogenous effector molecules as, for
example, the chatecholamines, is a reflection of this importance. The 30
odd drugs described in Chapter 3 represent a wide variety of structural
types; their biological activities are equally diverse. Consequently, it is
often not readily apparent just which parts of the structures form part of
the pharmacophore. Thus, compounds are included in this chapter largely
on the basis of structure. The grouping in the discussions that follow are
admittedly somewhat arbitrary.
1. ARYLCARBONYL DERIVATIVES
A relatively simple benzamide inhibitor of phosphodiesterase 4 has proven
useful for treating congestive obstructive pulmonary disease (COPD).
The synthesis of this compound begins by alkylation of the free phenol on
aldehyde 1 with chlorodifluromethane in the presence of base. Oxidation of
The Organic Chemistry of Drug Synthesis, Volume 7. By Daniel Lednicer
Copyright#2008 John Wiley & Sons, Inc.
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