PAUL S. ANDERSON
Dr. Anderson obtained his B.S. in chemistry from the University of Vermont in 1959 and his Ph.D. in chemistry with R. E. Lyle at the University of New Hampshire in 1963. After a postdoctoral appointment with Professor Meinwald at Cornell, he joined the Merck Sharp and Dohme Research Laboratories where he quickly moved from Senior Research Chemist to Research Fellow to Director of the Medicinal Chemistry Department to Vice President for Chemistry at the West Point research facility. He is currently Senior Vice President of Chemical and Physical Sciences for the DuPont Pharmaceuticals Company in Wilmington, Delaware.
Dr. Anderson and his co-workers at Merck were involved in research directed at the design and synthesis of molecules that act at neurotransmitter receptors such as MK-801, enzyme inhibitors such as simvastatin, a potent cholesterol lowering compound, and drugs for the treatment of glaucoma. These studies led to TRUSOPT, the first orally active carbonic anhydrase inhibitor for treating glaucoma and ZOCOR, the most frequently prescribed drug for lowering cholesterol levels.
More recently, Dr. Anderson has directed extensive medicinal chemistry efforts at Merck and DuPont Pharmaceuticals Company committed to discovery of new chemotherapy for AIDS. These efforts led to synthesis of inhibitors of the HIV-l reverse transcriptase and of HIV protease. The HIV protease inhibitor, CRIXIV AN, and the HIV reverse transcriptase InhIbitor, SUSTIV A, resulted from this work.
Dr. Anderson has served as Chairman of the Medicinal Chemistry Division of the American Chemical Society in 1987, Chairman of the 1991 Gordon Research Conference on Medicinal Chemistry and member (1985-1988) and then Chairman of a NIH Study Section on Bioorganic Chemistry and Natural Products, 1988-1989. More recently he has been a member of the National Advisory General Medicinal Sciences Council of the National Institutes of Health and the National Research Council, Board on Chemical Sciences and Technology. In 1997 he served as President of the American Chemical Society.
Dr. Anderson was the recipient for 1995 of the American Chemical Society's E. B. Hershberg Award for important discoveries in medicinally-active substances. He received a Doctor of Science Honoris Causa from the University of Vermont in 1998.
THE FRED J. ROBBINS LECTURESHIP
Pomona College takes great pleasure in presenting the Robbins Lecture for 2000, thirty-ninth in the series established by Mr. Robbins to bring Pomona College distinguished chemists to discuss their current research.
Mr. Robbins' interest in founding the lectureship came in part from his career as a metallurgical engineer and in part from his interest in creative research, which developed in his capacity as Chairman and President of a major specialty steel company.
"Understanding Drug Discovery"
"Understanding Drug Discovery-Some Principles"
"Discovery of New Therapy For Treatment of HIV Infection"
"Discovery of New Therapy For Treatment of Glaucoma"
"The Searcll For Neuroprotective
Agents"
B:OO p.m. Monday, February 14
4:30 p.m. Tuesday, February 15
4:30 p.m. Wednesday, February 16
4:30 p.m. Thursday, February 17
All lectures are held in Seaver Auditorium and are open to the public. Seaver Auditorium is located on College Avenue between 6'h and 71h Streets.
This year the Robbins Lectures will focus on understanding the drug discovery process. Modern drug discoveries have improved quality of life for millions of people during the 20th century. Antibiotics, drugs for treating high blood pressure, and elevated cholesterol levels, and most recently new therapies for managing HIV infection illustrate this point. The emphasis throughout the lecture series will be on how chemists and biologist have worked together to discovering new drugs.
The therapeutic usefulness of medicinally‑active substances, largely from nature, was known to early practitioners of medicine. However, a rationale process for discovering new medicines did not evolve until late in the 20th century. This process is focused on selection of an important therapeutic target followed by design of biological assays that link the objective to a physiologically relevant mechanism of action via a defined chemical entity. This process will be illustrated with specific "case histories".
A key step in the drug discovery process is the optimization of a lead molecule for pharmacological potency and selectivity. The tools of structural biology can be used to facilitate this step by identifying and focusing attention on important non‑covalent interactions between the drug candidate and its macromolecular target. Stereochemical detail is frequently important for obtaining proper alignment of complimentary features in the small molecule ligand and its target structure. For this purpose, X‑ray crystallography has been used to select stereochemically‑based tactics for optimizing inhibitors of HIV protease and carbonic anhydrase.
Drugs which block the life cycle of human immunodeficiency virus (HIV), the causative agent of Acquired Immunodeficiency Syndrome (AIDS), have been demonstrated to be anti‑viral drugs. Thus, inhibitors of HIV protease and HIV reverse transcriptase are anti‑viral agents. The clinical utility of these drugs is limited by the ability of the virus to rapidly generate resistant mutants. High resolution X‑ray structures of HIV‑1 protease, with and without bound inhibitors of this enzyme, have aided the process for designing optimal therapeutic agents. X‑ray structures of resistant mutants have been obtained. Analysis of these data may provide clues for the design of second generation inhibitors with improved therapeutic potential.
Drugs that are topically-effective are preferred in the treatment of glaucoma because this route of administration provides the desired local pharmacological action on the eye. The discovery of a carbonic anhydrase inhibitor that is topically-effective will be described.
Protection of the brain from damage associated with stroke remains an important objective for drug recovery. The discovery of dizoclipine (MK-801) as one approach to this problem will be discussed.