ABSTRACT
The selection of a lead compound can be based on rational design, the result
of screening thousands of compounds randomly drawn from a compound
library or a serendipitous event (recall the discovery of penicillin for instance).
Irrespective of its method of discovery, identification of a lead compound
is merely the start of the drug development process. The structure of the lead
compound must be optimized to produce the final active moiety. There are
many properties that can be altered: solubility, stability, efficacy, toxicity,
and taste, forming a non-exhaustive list. Good solubility is an essential
requirement for nearly all drugs and is discussed in Chapter 4. Stability (fully
discussed in Chap. 6) and taste masking are also important and can be controlled
to a large extent by careful formulation. Efficacy and toxicity, conversely, are
governed almost entirely by the structure of the molecule and its interaction
with biological entities (although formulation and dosing regimens can be
used to improve/mitigate such effects). Hence, the measurement (and if possible quantification) of such interactions plays an essential role in lead
compound optimization and is an area where calorimetric techniques can play
a vital role.
