were that simple, more and better drugs would already be available. Medicinal chemistry
is a science unto itself, a central science positioned to provide a molecular bridge between
the basic science of biology and the clinical science of medicine (analogous to chemistry
being the central science between the traditional disciplines of biology and physics).
From a very broad perspective, drug design may be divided into two phases:
- Basic concepts about drugs, receptors, and drug–receptor interactions (chapters 1–3).
- Basic concepts about drug–receptor interactions applied to human disease
(chapters 4–9).
The first phase comprises the essential building blocks of drug design and may be
divided into three logical steps:
- Know what properties turn a molecule into a drug (chapter 1).
- Know what properties turn a macromolecule into a drug receptor (chapter 2).
- Know how to design and synthesize a drug to fit into a receptor (chapter 3).
Knowledge of these three steps provides the necessary background required for a
researcher to sit down, paper in hand, and start the process of creating a molecule as a
potential drug for treating human disease.
Step 1 involves knowing what properties turn a molecule into a drug. All drugs may
be molecules, but all molecules are certainly not drugs. Drug molecules are “small”
organic molecules (molecular weight usually below 800 g/mol, often below 500).
Penicillin, acetylsalicyclic acid, and morphine are all small organic molecules. Certain
properties (geometric, conformational, stereochemical, electronic) must be controlled if
a molecule is going to have what it takes even to emerge as a drug-like molecule
(DLM).When designing a molecule to be a drug-like molecule and, hopefully, a drug,
the designer must have the ability to use diverse design tools. Now, computer-aided
molecular design (CAMD) is one of the most important design tools available. CAMD
incorporates various rigorous mathematical techniques, including molecular mechanics
and quantum mechanics. When using CAMD to design a drug, one must remember that
a drug molecule is complex and has sub-unit parts. Some of these parts enable the drug
to interact with its receptor, while other parts permit the body to absorb, distribute,
metabolize, and excrete the drug molecule. Once a drug-like molecule successfully
becomes a candidate for the treatment of a disease, it has graduated to the status of drug
molecule.
Step 2 involves knowing what properties turn a macromolecule into a receptor. All
receptors may be macromolecules, but all macromolecules are certainly not receptors.
Receptor macromolecules are frequently proteins or glycoproteins. Certain properties
must be present if a macromolecule is going to have what it takes to be a druggable
target. The receptor macromolecule must be intimately connected with the disease in
question, but not integral to the normal biochemistry of a wide range of processes.
Step 3 involves designing a specific drug-like molecule to fit into a particular drug-
gable target. During this task many molecules will be considered, but only one (or two)
will emerge as promising starting points around which to further elaborate the design
process. This prototype compound is referred to as the lead compound. There is a variety
6 MEDICINAL CHEMISTRY