Most drugs are molecules, but most molecules are not drugs. Every year, millions of
new molecules are prepared, but only a very small fraction of these are ever considered
as possible drug candidates. A chemical compound must possess certain characteristics
if it is to cross the hurdle from being an organic molecule to becoming a drug molecule.
Medicinal chemistryis the applied science that is focused on the design (or discovery)
of new chemical entities (NCEs) and their optimization and development as useful drug
molecules for the treatment of disease processes. In achieving this mandate, the medi-
cinal chemist must design and synthesize new molecules, ascertain how they interact
with biological macromolecules (such as proteins or nucleic acids), elucidate the rela-
tionship between their structure and biological activities, determine their absorption and
distribution throughout the body, and evaluate their metabolic transformations. Not sur-
prisingly, medicinal chemistry is multidisciplinary, drawing on theoretical chemistry,
organic chemistry, analytical chemistry, molecular biology, pharmacology, and bio-
chemistry. Despite these complexities, medicinal chemistry has a clear “bottom line”—
the design and discovery of drug molecules.

1.1 DEFINITION AND PROPERTIES OF A DRUG MOLECULE

1.1.1 What Is a Drug Molecule? What Is a Drug-Like Molecule?

A molecule is the smallest particle of a substance that retains the chemical identity of
that substance; it is composed of two or more atoms held together by chemical bonds
(i.e., shared electron pairs). Although molecules are highly variable in terms of struc-
ture, they may be organized into families on the basis of certain groupings of atoms
called functional groups. A functional group is an assembly or cluster of atoms that gen-
erally reacts in the same way, regardless of the molecule in which it is located; for
example, the carboxylic acid functional group (-COOH) generally imparts the property
of acidity to any molecule in which it is inserted. It is the presence of functional groups
that determines the chemical and physical properties of a given family of molecules.
A functional group is a centre of reactivity in a molecule.

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Basic Principles of Drug Design I

Drug molecules: structure and properties