185Introduction to Part II
Part I described the basics of medicinal chemistry and drug design. These principles
follow three basic activities:
- Design a molecule with drug-like properties.
- Select a receptor that is a potential drug target.
- Use design methods to identify and optimize a lead compound as a prototype drug.
From this sequence of activities, a number of observations can be made. Not all molecules
are drugs, but certain properties enable a molecule to be a drug-like molecule and poten-
tially a drug. Analogously, not all macromolecules are receptors, but certain properties
enable a macromolecule to be a druggable target. With these two basic facts in place, it is
then necessary to understand how to design drug-like molecules that can specifically
interact with drug targets. This process involves lead compound identification (via
rational drug design or high throughput screening, using either random or focused
libraries) followed by lead compound optimization (via quantitative structure–activity
relationship studies). Throughout the full spectrum of this design process, computer-
aided drug design with molecular mechanics and molecular orbital calculations is an
important design tool.
In order to discover therapeutic compounds, it is next necessary to connect these general
design principles to the specific reality of human disease. This means that the medicinal
chemist must have an organized knowledge of relevant biology and biochemistry and must
be able to integrate this knowledge with the principles of drug design, thereby enabling the
development of a therapeutic molecule. But how does one select a potential drug target for
the disease being studied? This requires a conceptual approach for drawing relationships
between druggable targets and specific human diseases. Such an approach is essential to
enable the mechanistic connection between a disease and a molecule. There are many
approaches by which this conceptual connection can be developed.