Ebook: Medicinal Chemistry

This textbook is an overview of the subject of medicinal chemistry within the context of drug design and
discovery. Both of us were trained as synthetic organic chemists and had our “first” careers in medicinal
chemistry departments at major pharmaceutical companies. Upon moving into academia, we both took on
teaching a one-semester class in medicinal chemistry. Anyone who has taught this type of course quickly
realizes the difficulty in bringing together the many aspects that comprise this subject, such as organic
chemistry, pharmacology, and biochemistry, as well as introducing therapeutic areas in medicinal chemistry in
just one semester. After teaching this course for many years using various review articles as text, as well as
material written ourselves, we decided to write this textbook. We have tried to write a text that includes the
historical background of drug discovery but emphasizes modern practices in design, discovery, and
development. We focus on drug targets and how current knowledge of these targets drives medicinal chemistry
and drug discovery. While it is not possible to cover all therapeutic areas in a one-semester text, selected areas
and classes of drugs are also included. Overall, we intend for this text to meet the need for a modern, onesemester textbook that ties together the many different aspects of medicinal chemistry as it is currently
practiced.
The target audience is primarily upper-level undergraduate students and beginning graduate students in
organic chemistry and medicinal chemistry. Other students who might find the text useful include pharmacy
students and anyone planning to pursue a career in the drug discovery field. In addition to science majors, we
have had students from fields as diverse as finance, engineering, and biomedical ethics take our courses, all
with a common interest in learning about drug discovery. The book should also be useful for professional
scientists, such as chemists, biologists, and patent professionals, who are just entering the drug discovery field
and may not have had direct experience with medicinal chemistry. It is expected that those using this textbook
have a basic knowledge of organic chemistry as well as basic biology.
To present this broad subject in a way that is logical and covers essential topics in a one-semester format,
our approach is to divide the text into three sections. PART I, Drug Discovery and Development: the first five
chapters cover historical background in drug discovery, as well as the modern drug discovery and development
process, with an emphasis on medicinal chemistry strategies used in various phases. These chapters give the
essential background of hit and lead discovery, modifications driven by knowledge of both target and
pharmacophore structure, common medicinal chemistry strategies, and the central importance of
pharmacokinetics. They provide the background that subsequent chapters build upon. PART II, Classes of
Drug Targets: Chapters 6-9 focus on the major drug targets, namely, their structure and function and how
medicinal chemists approach each. Examples of specific drugs developed for each type of target are included.
Targets include receptors and ion channels, enzymes, protein-protein and lipid interactions, and nucleic acids.
Each of those is broken down into more specific classes of important drug targets. These chapters can be
covered in any order but reference topics in Chapters 1-5. PART III, Selected Therapeutic Areas: the final
chapters, 10-13, are devoted to selected important therapeutic areas. While there are many more chapters that
could have been written on additional areas of interest, these topics were selected as examples that tie together
components introduced in the earlier chapters and represent both historically important agents and future
opportunities. Those topics included are anti-cancer, antibacterial, and antiviral drugs and drugs acting on the
central nervous system. A subset of Chapter 13 is devoted to drugs of abuse, informed by student interest on
this topic. Any of these last chapters on specific therapeutic areas can be considered optional or used
independently, but they also rely on the material covered in Chapters 1-9.