The chemistry of carbon-based molecules—their structures, intermolecular interactions, and reactivity—underlies life as we know it and thus also the beneficial (and sometimes undesired) effects of the medicines we use. The fact that rather simple organic molecules can be profoundly effective in treating human disease in all its complexity must rank among the most significant findings of medicine and basic science. For many students, this realization foments a desire to pursue a career in one of the various fields related to the discovery, study, or appropriate administration of medicines. In my own case, this meant embarking on the study of organic chemistry and learning how to synthesize organic molecules in the laboratory. Later, as a medicinal chemist working in the pharmaceutical industry, I experienced the thrill of seeing a few milligrams (mere specks!) of a newly synthesized compound cure an otherwise lethal infection in a mouse. A few such compounds would later be destined for studies in human patients, beginning the long and often perilous path toward the approval of a new drug.
This textbook is informed by my experiences as a practicing medicinal chemist and as an educator of pharmacy students at the University of California, San Francisco. In its organization and content, the text is largely based on a semester-long course in organic chemistry taught to first-year PharmD students at UCSF. It is intended as a teaching textbook, a companion for students of pharmacy or medicinal chemistry, that can be covered in its entirety in a single semester. Given this, the text is necessarily limited in its scope and is not intended to replace any of the excellent and comprehensive handbooks of medicinal and pharmaceutical chemistry that are available. What is covered here are those topics we have found most relevant and instructive in providing students of pharmacy with a solid grounding in organic chemistry as it relates to drug structure and action.
The first four chapters of the text cover the fundamentals of drug structure and binding—the nature of the chemical bonds in drug structure, the types of non-covalent intermolecular interactions drugs form with their targets, and their three-dimensional shape and conformations. The final four chapters are concerned with chemical reactivity relevant to drug action—the reactivity of (some) drugs toward their targets, the metabolism of nearly all drugs, and the reactions carried out by the enzymes that modify drugs or can be targeted by them. Throughout the text, the discussion is intertwined with illustrative examples of drug synthesis, action, or metabolism. Also, each chapter concludes with a drug case study selected to emphasize and reinforce the concepts introduced in that chapter.
I am indebted to a number of individuals without whom this project could never have happened. It has been a distinct privilege to interact with the bright and inquisitive PharmD students that UCSF is fortunate enough to attract. Their willing feedback as to what is and is not working in the classroom has shaped how we teach organic chemistry at UCSF, and this in turn is reflected in the final form of the book. I must likewise acknowledge current and former UCSF colleagues (Susan M. Miller, Thomas Scanlan, and Paul Ortiz de Montellano) who contributed to developing the organic chemistry curriculum in the PharmD program. The editors and production designers at McGraw-Hill Education have been a pleasure to work with. I would especially like to thank Michael Weitz, Peter Boyle, and Ruchika Abrol for their assistance and encouragement. I am grateful to Professor Peter Beak (University of Illinois at Urbana-Champaign) for reading the final manuscript. Last but not least, I must thank my coauthors and contributors (John Flygare, Dmitry Koltun, Jie Jack Li, and Susan M. Miller), top-notch researchers and educators who put their own stamp on the chapters to which they contributed. We hope that this first edition of The Organic Chemistry of Medicinal Agents will prove useful for students and instructors alike and we welcome suggestions for improvements and additions to future editions.