Medicinal Chemistry

3.3.2 Need for Efficient Synthetic Methods

Typically, medicinal chemists work in either academic or industrial research laboratories.
Accordingly, they tend to develop “research level” syntheses. At the research level, it is
acceptable for a synthetic scheme to employ unusual catalysts or large amounts of organic
solvents. However, this is not acceptable at the “scale-up level.” For a drug molecule to be
successful, it must also be affordable. If a drug costs $85 per milligram to synthesize and
will be administered at 60 mg/day for many months, then it will not be a commercially
viable drug. If a drug is to be successful it will have to be produced in large quantities in
an industrial setting, necessitating the implementation of syntheses that are “scalable,” effi-
cient, and environmentally friendly. A synthetic scheme with fewer steps and employing
water as a preferred solvent has distinct advantages over a technically complicated, low-
yield synthesis that uses large quantities of organic solvents that are difficult to dispose of.
Thus, there are some differences between a classical synthetic organic chemist and a
synthetic medicinal chemist. The classical synthetic organic chemist is proud of a com-
plex multistep synthesis which may, regrettably, have a low yield. The synthetic medi-
cinal chemist is pleased to design a molecule that can be synthesized in as few steps as
possible, hopefully with a high yield and few by-products. Figures 3.4.–3.6 present syn-
theses of three common drug molecules.

3.3.3 Need for a Robust Biological Model for Compound Evaluation

Once the lead compound has been synthesized, it is next necessary to biologically eval-
uate it. A number of very important characteristics go into making a biological assay
useful. Ideally, the assay should be rapid, cost-effective, efficient, and easy to implement.

130 MEDICINAL CHEMISTRY

Figure 3.3 The synthon approach: example of a retrosynthetic approach to the synthesis of
cyclohexanol.