arrangement of atoms in a drug molecule that are responsible for the metabolic
properties. Since functional groups are responsible not only for drug–receptor interac-
tions but also for metabolic properties, the metabophore and the pharmacophore tend to
be inextricably overlapped. Nevertheless, from the viewpoint of drug design, it is some-
times possible to manipulate the structure of either the pharmacophore or the molecu-
lar baggage portions of the drug molecule to achieve a metabophore that overcomes
problems with liver-mediated first pass effects or that either hastens or delays renal
excretion (see figure 1.4).
20 MEDICINAL CHEMISTRY
Figure 1.4 A drug molecule contains many parts. The bioactive face is the portion of the drug
molecule that interacts with the receptor; the remainder of the molecule, called molecular baggage,
holds the bioactive face in a desired geometry. The pharmacophore is the arrangement of mole-
cules that permits the bioactive face to interact with the receptor. The toxicophore is the fragment
that is responsible for toxicity; the metabophore is the fragment that is responsible for metabolism.
If these various fragments are separate (as in B), then toxicity can be “designed out of the drug
molecule”; if they overlap (as in C), then it may be impossible to separate the toxicophore from
the pharmacophore. It is sometimes possible to replace all or part of the pharmacophore with a
biologically equivalent fragment called a bioisostere.