The Organic Chemistry of Drug Design and Drug Action

Professor Richard B. Silverman received his B.S. degree in chemistry from The Pennsylvania State University in 1968 and his Ph.D. degree in organic chemistry from Harvard University in 1974 (with time off for a two-year military obligation from 1969-1971). After two years as a NIH postdoctoral fellow in the laboratory of the late Professor Robert Abeles in the Graduate Department of Biochemistry at Brandeis University, he joined the chemistry faculty at Northwestern University. In 1986, he became Professor of Chemistry and Professor of Biochemistry, Molecular Biology, and Cell Biology. In 2001, he became the Charles Deering McCormick Professor of Teaching Excellence for three years, and since 2004 he has been the John Evans Professor of Chemistry. His research can be summarized as investigations of the molecular mechanisms of action, rational design, and syntheses of potential medicinal agents acting on enzymes and receptors. His awards include DuPont Young Faculty Fellow (1976), Alfred P. Sloan Research Fellow (1981-1985), NIH Research Career Development Award (1982-1987), Fellow of the American Institute of Chemists (1985), Fellow of the American Association for the Advancement of Science (1990), Arthur C. Cope Senior Scholar Award of the American Chemical Society (2003), Alumni Fellow Award from Pennsylvania State University (2008), Medicinal Chemistry Hall of Fame of the American Chemical Society (2009), the Perkin Medal from the Society of Chemical Industry (2009), the Hall of Fame of Central High School of Philadelphia (2011), the E.B. Hershberg Award for Important Discoveries in Medicinally Active Substances from the American Chemical Society (2011), Fellow of the American Chemical Society (2011), Sato Memorial International Award of the Pharmaceutical Society of Japan (2012), Roland T. Lakey Award of Wayne State University (2013), BMS-Edward E. Smissman Award of the American Chemical Society (2013), the Centenary Prize of the Royal Society of Chemistry (2013), and the Excellence in Medicinal Chemistry Prize of the Israel Chemical Society (2014). Professor Silverman has published over 320 research and review articles, holds 49 domestic and foreign patents, and has written four books (The Organic Chemistry of Drug Design and Drug Action is translated into German and Chinese). He is the inventor of LyricaTM, a drug marketed by Pfizer for epilepsy, neuropathic pain, fibromyalgia, and spinal cord injury pain; currently, he has another CNS drug in clinical trials. Dr. Mark W. Holladay is Vice President of Drug Discovery and Medicinal Chemistry at Ambit Biosciences (San Diego, California) where he leads drug discovery programs in oncology and autoimmune diseases and has contributed to compounds in clinical development. He began his drug hunting career at Abbott Laboratories where he achieved the position of Volwiler Associate Research Fellow as a medicinal chemist and project leader in the Neurosciences Research Area. He also conducted collaborative drug discovery research as a member of contract research organizations including Biofocus and Discovery Partners International. He is a co-author on over 70 peer-reviewed research articles, reviews, or chapters and is named as an inventor on over 40 patents and patent applications. Dr. Holladay earned his undergraduate degree from Vanderbilt University, his Ph.D. at Northwestern University under the direction of Professor Richard B. Silverman, and conducted postdoctoral studies with Professor Daniel H. Rich at the University of Wisconsin-Madison. Dr. Jose I. Juncosa, Jr. holds a Licentiate in Chemistry (summa cum laude) from Simon Bolivar University in Caracas, Venezuela and a Ph.D. in Medicinal Chemistry and Molecular Pharmacology from Purdue University in West Lafayette, Indiana, USA, having been mentored by Drs. Jose E. Villamizar and Nieves Canudas (undergraduate), Dr. David E. Nichols (graduate) and Dr. Richard E. Silverman (postdoctoral). His research currently focuses on the synthesis of selective agonists for the serotonin 5-HT2A receptor and the development of new experiences for the experimental training of organic chemistry students. Dr. Juncosa has coauthored several publications within the field of Medicinal Chemistry, in the areas of semisynthesis of natural products, the molecular modeling of GPCRs and PLP-dependent enzymes, and the design and synthesis of druglike compounds, including selective agonists for dopamine and serotonin receptors and inactivators of GABA and ornithine aminotransferases. The latter work has resulted in a patent and a drug candidate currently in preclinical trials. He is currently an Associate Professor of Chemistry at Salisbury University, in Salisbury, Maryland, USA., where he teaches courses in General, Organic and Medicinal Chemistry. Dr. Juncosa also holds a degree as a Performing Professor of Piano. Dr Fengtian Xue have a broad training in organic synthesis, medicinal chemistry, and drug discovery with specific training and expertise in early-stage development of small molecule therapeutics. Dr Xue received his PhD at Brown University in 2007, and continued his postdoctoral training in the Silverman Laboratory between 2007 and 2009 at Northwestern University. After a two-year teaching experience at University of Louisiana at Lafayette, in 2011 Dr Xue started independent research lab at University of Maryland Baltimore, where he is currently an Associate Professor in the Department of Pharmaceutical Sciences. Dr Xue’s graduate and postdoctoral studies focus on design, synthesis and biological evaluations of small molecule inhibitors for disease-related enzymes (e.g., serine protease plasmin and neuronal nitric oxide synthase). His studies identified novel drug candidates for metastasis cancer and neurodegenerative diseases. During this period, Dr Xue published as first author in 15 research articles. In addition, he is also an inventor of seven patent applications. Dr Xue has been leading his independent lab for seven years. The Xue Laboratory has a broad interest in the development of small molecule therapeutics for important human diseases including bacterial / parasitic infections, cancer, metabolic disorders, and neurodegenerative diseases, with over 50 research articles and seven patent applications.

1. Introduction 2. Lead discovery 3. Lead modification 4. Receptors 5. Agonists and antagonists of receptors 6. Enzymes 7. Enzyme inhibition 8. DNA and RNA 9. DNA- and RNA-interactive agents 10. Other drug targets 11. Pharmacokinetics 12. Drug resistance and drug synergism 13. Prodrugs and delivery systems