3 An Introduction to Drug Discovery
3.1 Introduction
Drug discovery is part luck and part structured investigation. At the begining of
the 19th century it was largely carried out by individuals but it now requires
teamwork, the members of the team being specialists in various fields, such as
medicine, biochemistry, chemistry, computerized molecular modelling, pharma-
ceutics, pharmacology, microbiology, toxicology, physiology and pathology.
This chapter outlines a general approach to drug discovery by design. It also
introduces the stereochemical and water solubility factors that should be taken
into account when selecting a structure for a lead compound.
The approach to drug design depends on the objectives of the design team.
These objectives will normally require a detailed assessment of the pathology of
the disease and in some cases basic biochemical research will be necessary before
initiating a drug design investigation (Figure 3.1). The information obtained is
used by the team to decide what intervention would be most likely to bring
about the desired result. Once the point of intervention has been selected, the
team has to propose a structure for a lead compound that could possibly bring
about the required change. This frequently requires an extensive literature and
database search to identify compounds found in the organism (endogenous
compounds) and compounds that are not found in the organism (exogenous
compounds) that have some biological effect at the intervention site. Molecular
modelling techniques (see Chapter 5) are sometimes used to help the team reach
a decision. In many cases, a number of structures are found to be suitable, but
the expense of producing drugs dictates that the team has to choose only one or
two of these compounds to either act as the lead or to be the inspiration for the
lead compound. The final selection depends on the experience of the team.
Fundamentals of Medicinal Chemistry, Edited by Gareth Thomas
#2003 John Wiley & Sons, Ltd
ISBN 0 470 84306 3 (Hbk), ISBN 0 470 84307 1 (pbk)