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Chemistry Professor Publishes Thorough Text on Multidisciplinary Field of Medicinal Chemistry

by Bill Giduz
Prof. Erland Stevens and Natalia Spitha
Natalia Spitha '16 is conducting research on medicinal chemistry with Prof. Stevens this summer.

Professor Erland Stevens, chair of the chemistry department, has published a book covering a field that crosses academic boundaries more broadly than most chemistry texts.

Medicinal Chemistry: The Modern Drug Discovery Process is based on Stevens' academic training as an organic synthetic chemist, and explain in detail the chemical manipulations necessary to create compounds that may be effective against disease. But the book also touches on the complex web of regulatory, commercial, ethical and political issues involved in creating drugs.

Stevens was born and raised in Ashland, Ky., and traces his interest in chemistry to a high school teacher-Richard "Doc" Patterson. "He was known to be tough, but there was a lot of discussion and interaction in class," Stevens said. "On almost all his tests he would add the phrase 'Justify your answer.' He was interested not only in your getting it right, but also in how you got it. Because of him I ask that on some of my own tests to this day."

Stevens attended Duke University and earned his bachelor's degree in chemistry. He conducted doctoral work at the University of Michigan, testing new ways making heterocyclic compounds, many of which are used in pharmacological drugs.

Though it was good training in the field, the work was highly theoretical, was difficult to conduct, and generated a lot of waste.

He received his Ph.D. in May 1997, and applied for a post-doctoral appointment at Scripps Research Institute in California in the laboratory of Barry Sharpless, who was conducting studies in asymmetric synthesis that later earned him a Nobel Prize. Stevens was eager to get out of heterocycles and into asymmetric synthesis. But when he was accepted at Scripps he found Sharpless was redirecting his lab to investigate simple, efficient methods to make the heterocyclic compounds Stevens had wanted to leave behind.

But the idea of improved methods of creating heterocycles appealed to Stevens, and his prior training in the field proved valuable in Sharpless's lab. "At Michigan I studied things that weren't practical, but Sharpless's lab was all about practicality, about simple, robust and practical methods. I learned to appreciate that aspect of chemistry at Scripps."

Stevens began teaching at Davidson in 1998, and brought the methodology of simple chemistry with him. The chemistry department primarily needed Stevens to teach organic chemistry, which enrolls a large number of science-oriented students. But the department also recognized in Stevens an opportunity to use his training to develop a course in medicinal chemistry that would appeal to non-chemistry majors.

"It's not easy to find something for students to work with that's clean, simple, practical and new," Stevens said. "But the work with heterocycles in Sharpless's lab gave that to me."

He developed his medicinal chemistry course and first taught it in 2001-2002. Despite his knowledge of the subject, he found teaching the new course to be "humbling." "I was often learning the material just ahead of my students," he said. "It took a lot of work."

But the field interested him, and he was pleasantly surprised at the level of student engagement in the class. He attributed that to the fact that medicinal chemistry is an area that touches the public more personally than most fields of chemistry. Stevens explained, "Undergraduate chemistry is generally very theoretical, and doesn't always cover application of theory. But students want to see where the rubber meets the road, and in medicinal chemistry we get to do that. Everyone knows someone with a good or bad encounter with medicine, and the process of developing drugs, their place in the health care system, and their price is constantly in the news. Medicinal chemistry is highly applied to our daily lives."

In fact, the course's broad reach has led to its listing as a qualifying course in four academic concentrations --biochemistry, neuroscience, genomics, and medical humanities.

Stevens has now taught the course at Davidson a half-dozen times, and after his stint as department chair expires he hopes to teach it every other year.

Prof. Erland Steven's book

The idea for the book, Medicinal Chemistry: The Modern Drug Discovery Process, dawned on Stevens as he learned more about the subject. In the summer of 2002 he attended a week-long school on medicinal chemistry at Drew University, and he began attending lectures on medicinal chemistry presented at the twice-annual meetings of the American Chemical Society.

He said the commercial importance of medicinal chemistry is on full view at meeting lectures, which he described as "bedlam." Presentations are heavily attended because new medicines are announced that can be tremendously profitable. Presenters reveal the molecular structure and characteristics of new drugs they've developed. It's extremely valuable information for rival companies because they might be able to alter the structure in their own labs to create a new or enhanced products. Though it's prohibited to take pictures of the presenter's illustrations, attendees try to do so anyway, and news about the new drug may be on the Internet within minutes.

As Stevens delved more deeply in the field, he realized that none of the few undergraduate textbooks on medicinal chemistry were right for his course, and determined to write his own. "There was nothing that provided students with what they needed to appreciate a conference talk on medicinal chemistry," he said. "That became the driving force behind the book."

He signed a contract in 2006 to produce the book as part of Pearson Publishing's "advanced chemistry" series.

Chapters include possible points of intervention for a drug, discovery of weakly active drug hits through screening, selection of drug leads, optimization of a clinical drug candidate, and some details of drug synthesis.

Each chapter includes learning objectives, case studies, end-of-chapter summaries, highlighted keywords, sample calculations, figures of molecules being discussed, and conceptual end-of-chapter problems.

Chapter two of Stevens' 400-page book provides an overview of the process of taking a drug all the way from concept through marketing, including extensive and expensive trials on animals and humans, and determination by the Food and Drug Administration that the drug is safe and effective. But most of Medicinal Chemistry covers the drug discovery process through words and many illustrations of the chemical structures of drugs and drug candidates.

Prof. Erland Stevens Stevens explained that the primary work of medicinal chemists is modifying molecular structure of known compounds to improve their function. The drug discovery process often begins with large collections of molecules held by a drug company. Each compound in the collection, which may include over a million different molecules, is tested for biological activity. The most active compounds, called hits, are further screened for factors such as transportability within the body, effectiveness against disease, ease of synthesis, improved function and even patentability. The structure of a promising compounds are further manipulated until the molecules demonstrate drug-like biological activity.

Stevens recognized early on that heterocycles would be excellent candidates not only for teaching medicinal chemistry, but for student research as well. They are relatively easy and safe to work with, they have real application in the world, and the research would be covering new ground rather than replicating prior research.

Three years ago Stevens and Professor of Biology Dave Wessner received funding from the National Institutes of Health to synthesize compounds that may be effective against viruses. They have created several molecules they hope will be effective in slowing the progression of mononucleosis, herpes and hepatitis C, and this summer will be sending them to thea NIH for effectiveness testing. Several students have been working with the two professors over the years, and some have presented papers and posters about their work.

Feedback from peers in the field gives Stevens hope that his book will be popular in academic circles. One professor told Stevens he has taught medicinal chemistry for 15 years, and never until now seen a textbook that warranted purchase by his students.