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Medicinal chemistryStructure-activity relationships (SAR) describe how the structure of related drugs
influences their behaviour, for example whether they are agonists or antagonists. In
order to understand how differences in drug structure can affect activity it is nec-
essary to appreciate drug development methods and some basic organic chemistry.
Once the properties of the contributing groups are understood, then it becomes eas-
ier to predict the likely behaviour of a drug molecule compared with the parent drug.
Inaddition, knowledge of the structural properties of a drug may help us appreciate
some of their physicochemical properties, such as their solubility in oil and water,
their pKa values and whether they are weak acids or bases. These in turn help us
understand the pharmacokinetic behaviour of a drug.
Drug design starts with a lead compound that has the required action in an animal
model, but is not necessarily ideal; for example, the drug may resemble a neuro-
transmitter or be an enzyme inhibitor. By adding various functional groups to this
compound it is possible to develop a more specific drug to target the required sys-
tem. Once a compound with the most favourable pharmacodynamic effects is found,
further modifications may be made to make the drug’s pharmacokinetic behaviour
more desirable.
Inthis chapter we will introduce some basic organic chemistry and identify the
structures associated with drugs commonly used in anaesthesia. Those basic struc-
tures that should be readily identified are mentioned briefly below, together with
diagrams of their structures and examples relevant to anaesthesia. These should be
used in conjunction with a description of drug activity in SectionsII–IV.
Organic chemistry is the study of carbon-based compounds. The position of car-
bon in the middle of the periodic table (Group 4) gives it an atomic structure that
can form covalent bonds with elements from either end of the table. This contrasts
with inorganic chemistry, where ionic bonds are most common. Covalent bonds
are stronger than ionic bonds and do not interact readily with water, making many
organic molecules insoluble in water. By the addition of functional groups (such as
hydroxyl –OH or amine –NH 2 ) these organic compounds can become water-soluble.
Organic molecules are the basis of life, from DNA to structural proteins and chemi-
cal messengers. Knowledge of these basic building blocks and signalling systems is
crucial to an understanding of how therapeutic agents modify existing physiological
processes at the molecular level.