Zoran Rankovic & Richard Morphy 
Lead Generation Approaches in Drug Discovery 

An integrated overview of modern approaches to lead
discovery

Lead generation is increasingly seen as a distinct and
success-determining phase of the drug discovery process. Over
recent years, there have been major advances in the understanding
of what constitutes a good lead compound and how to improve the
chances of finding such a compound. Written by leading scientists
and established opinion leaders from industry and academia, this
book provides an authoritative overview of the field, as well as
the theory, practice, and scope, of the principal Lead
Generation Approaches in Drug Discovery, including:

* The evolution of the lead discovery process, key concepts,
current challenges, and future directions

* Strategies and technologies driving the high-throughput
screening (HTS) approach to lead discovery, including the shifting
paradigms in the design of compound collections and best practice
in the hit confirmation process

* Knowledge-based in silico or ‘virtual’ screening

* Theory and practice of the fragment-based approach to lead
discovery

* The opportunities and challenges presented by multi-target drug
discovery (MTDD)

* De novo design of lead compounds and new approaches to
estimating the synthetic accessibility of de novo-designed
molecules

* The impact of natural products on drug discovery, and potential
of natural product-like compounds for exploring regions of
biologically relevant chemical space

* Using early screening of hits and leads for metabolic,
pharmacokinetic, and toxicological liabilities to reduce attrition
during the later phases of drug discovery

* The utility of parallel synthesis and purification in lead
discovery

With each topic supported by numerous case studies, this is
indispensable reading for researchers in industry and academia who
wish to keep up to date with the latest strategies and approaches
in drug discovery.

Table of Content

PREFACE.

CONTRIBUTORS.

1 Lead Discovery: The Process (William F. Michne).

2 High Throughput Screening Approach to Lead Discovery (Zoran
Rankovic, Craig Jamieson, and Richard Morphy).

3 In Silico Screening (Dagmar Stumpfe, Hanna Geppert, and
Jürgen Bajorath).

4 Fragment-Based Lead Discovery (Jeffrey S. Albert).

5 Design of Multitarget Ligands (Richard Morphy and Zoran
Rankovic).

6 De novo Drug Design (Gisbert Schneider, Markus
Hartenfeller, and Ewgenij Proschak).

7 Role of Natural Products in Drug Discovery (Hugo Lachance,
Stefan Wetzel, and Herbert Waldmann).

8 Early Screening for ADMET Properties (Dennis A.
Smith).

9 Role of Chemistry in Lead Discovery (Roland E. Dolle and
Karin Worm).

INDEX.

About the author

ZORAN RANKOVIC is a Senior Research Fellow and
Associate Director in Medicinal Chemistry at Schering-Plough
Research Institute, UK. He received his Ph D in organic chemistry
from the University of Leeds (UK) before starting his medicinal
chemistry career in 1995 at Organon, UK. Since then, working on
projects over a range of therapeutic areas, including psychosis,
analgesia, and cardiovascular and bone diseases, he gained
extensive experience in all stages of the drug discovery process,
including lead generation. From this work, Dr. Rankovic has
authored or coauthored over fifty scientific publications, book
chapters, and patents, and has given invited lectures at numerous
international conferences.

RICHARD MORPHY is a medicinal chemistry section head at
Schering-Plough Research Institute (SPRI) at Newhouse, Scotland. He
has twenty years’ experience in the pharmaceutical industry,
previously working for Celltech and Organon on a wide range of
oncology, inflammation, psychiatry, and analgesia projects. In
addition to his extensive experience of the lead discovery process,
he has a keen interest in the development of medicinal chemistry in
emerging economies and is an opinion leader in the area of
multi-target drug discovery.