Medicinal Chemistry

once the hydrocarbon chains are in sufficient proximity, van der Waals forces become
operative between them.

2.3.8 Selection of Drug–Receptor Binding Forces in Drug Design

When designing a drug for a particular therapeutic application, the drug designer has
the opportunity to engineer functional groups capable of specific drug–receptor binding
interactions into the drug molecule. As discussed in chapter 1, a drug molecule is a col-
lection of geometrically arranged functional groups displayed on a molecular frame-
work. These functional groups establish interactions with the drug receptor by one or
more of the various binding forces discussed above.
When designing a drug, the designer wishes to have an energetically favorable and
geometrically optimal interaction with the receptor site. This may be achieved in two
strategies: (i) by having multiple points of contact between the drug molecule and the
receptor (i.e., the pharmacophoric pattern in the drug matches to several complementary
sites on the corresponding receptor site); and (ii) by having each individual point of
contact between the drug and the receptor as energetically strong as possible.

74 MEDICINAL CHEMISTRY

Figure 2.1 Schematic diagram of the hydrophobic interaction between two leucine side chains of
a protein. By displacing part of the hydrate envelope, the two alkyl side chains occupy the same
water “cavity” while many of the water molecules (represented by circles) become randomized.
Thus the entropy of the system increases, resulting in a favorable stabilization.