SCIENCE & TECHNOLOGY
2002
PERKIN
MEDAL
DRUG DISCOVERER PAUL ANDERSON Award recognizes Wilmington, Del.-based chemist's leadership in medicinal chemistry MICHAEL FREEMANTLE, C&EN LONDON
P
AUL S. ANDERSON CREDITS HIS
father for sparking his fascination with chemistry. "When I was 12 years old, my father started teaching me how to do chemistry experiments at the kitchen sink at home," he says. "He showed me, for example, how to make hydrogen and oxygen, and how oxygen supports combustion, whereas hydrogen burns." That fascination has led to a distinguished career in medicinal chemistry For almost 4 0 years, Anderson and the colleagues whose research he has directed have designed and synthesized numerous pharmaceutical compounds that have achieved regulatory approval. For these contributions to medicinal HTTP://PUBS.ACS.ORG/CEN
chemistry as well as his leadership in drug discovery, Anderson has been named winner ofthe 2002 Perkin Medal. Recognized as one the U.S. chemical industry's highest honors, the gold medal is awarded annually by the American Section ofthe London-based Society of Chemical Industry (SCI) for outstanding work in applied chemistry in the U.S. Anderson will receive the medal at the society's annual dinner in New % r k City this week. THE MEDAL WAS established in 1906 to commemorate the discovery of the first commercial synthetic dye, mauveine, by English chemist Sir William H. Perkin (1838-1908) in 1856. The recipient of the medal is selected by an award jury com-
posed ofrepresentatives from SCI's American Section, the American Chemical Society the American Institute of Chemical Engineers, the Electrochemical Society, the American Institute of Chemists, and the American Section of Société de Chimie Industrielle. Anderson stresses that the honor is a tribute not just to himselfbut also to his research and development colleagues. "Drug discovery is a team sport, involving chemists, biologists, pharmacologists, and others," he tells C&EN. "Every member of the team works closely together, bringing to the table the skills, strengths, and knowledge required for success. I am delighted that all the people I've had the privilege ofworking with over the past 37 years or so have been recognized with this award of the Perkin Medal." Born in February 1938, Anderson received a B.S. degree in chemistry from the University of \ermont in 1959 and a Ph.D. degree in chemistry from the University of New Hampshire in 1963. "I had never heard of the term 'medicinal chemistry' until graduate school," Anderson says. "I attended a special seminar on the topic by my mentor, Robert Lyle. I'd obviously heard about pharmaceutical companies, but it had never occurred to me that chemists actually discovered drugs. So I got very excited about using chemistry for that purpose." Following postdoctoral work at Cornell University, Anderson joined the medicinal chemistry department of Merck Sharp & Dohme Laboratories as senior research chemist in 1964. He became a research fellow in 1969, and after several positions of increasing responsibility in the department, he was appointed an executive director in 1980 and vice president for chemistry at Merck's West Point, Pa., research facility in 1988. In 1994, Anderson was part of the research contingent that Merck contributed to the DuPont-Merck Pharmaceutical joint venture. Following DuPont's buyout of Merck's interest in the venture, he served as senior vice president for chemical and physical sciences at DuPont Pharmaceuticals. He is now vice president of drug discovery at Bristol-Myers Squibb, which acquired DuPont Pharmaceuticals in October of last year. Anderson and his colleagues at Merck were involved in research on the design and synthesis of molecules for treating glaucoma and high cholesterol levels and for preventing ischemic brain damage resulting from seizure, cardiac arrest, or stroke. He also directed the development C&EN / MARCH
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SCIENCE & TECHNOLOGY ofmedications for treating coronary heart disease and for fighting H I V and AIDS. "Most of the projects Fve been associat ed with depend on enzyme inhibition to achieve their therapeutic effect," Anderson explains. icWe select a biochemical mecha nism that is either the causative factor or a contributor to the disease for which we're trying to provide a therapy We then look at the mechanism and decide where we want to step in and interrupt the chemistry" A GOOD EXAMPLE is simvastatin. Pro duced by Merck, simvastatin is alipid-lowering agent marketed as Zocor. The drug reduces the total amount of cholesterol in blood by lowering undesirable LDL (lowdensity lipoprotein) cholesterol while in creasing "good" H D L (high-density lipoprotein) cholesterol. "Simvastatin was first synthesized in Merck's department ofmedicinal chemistry in the early 1980s," Anderson says. "It was the first drug I was associated with to reach the marketplace and is still used all around the world." The compound is an inactive lactone that is hydrolyzed to an active hydroxyacid form after oral ingestion. It inhibits HMG-
CoA reductase, an enzyme that catalyzes an early and rate-limiting step in the biosynthesis of cholesterol. During the 1980s, Anderson and col leagues also carried out seminal work on the design and synthesis of ligands that have high affinity and specificity for neuro-
NMDAreceptor, that then allowed a lethal influx of calcium into brain cells.
