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William F. Michne, Ph.D.

Dr.William F. Michne was born in Albany, New York, on December 9, 1942, the youngest of three children. His father was a welder in the repair shops of the New York Central Railroad, and his mother was a part-time waitress. He received a Bachelor degree in chemistry from Siena College in 1964, and began immediate employment at the Sterling-Winthrop Research Institute as an Assistant Research Chemist. Simultaneously, he began graduate studies in organic chemistry at Rensselaer Polytechnic Institute, earning a doctorate in 1968.

His first major scientific achievement was the synthesis of a series of benzomorphanones. These analogs of the opiate alkaloid morphine exhibited unusual pharmacological properties, both in vitro and in vivo, relative to all previously studied compounds in this class. While they were very potent in assays for morphine-like behavior, their activity was rather insensitive to reversal by naloxone, a morphine antagonist. Further study of one of these compounds, ketazocine, led to the discovery of the kappa opioid receptor subtype. Ketazocine advanced to human clinical trials for pain. The single enantiomer ethylketazocine, more commonly known as EKC, advanced to preclinical development as an intravenous anesthetic, and was widely used in early studies of the kappa receptor.

The next major phase of his career extended his work on benzomorphans to analogs of the exceedingly potent opiates known as thebaine Diels-Alder adducts. He and his co-workers devised a stereospecific synthesis of a very challenging construct of three contiguous asymmetric centers two of which were adjacent and quaternary. The synthesis was eventually carried out on multi-kilogram scale to support the advancement of three compounds. One of them, tonazocine, was the first non-peptide delta opioid agonist, and was clinically as efficacious as morphine.

Over the next decade his career advanced with positions of increasing responsibilities. Research groups under his direction had highly focused programs in the areas of pain and inflammation, cardiovascular agents, anti-viral agents, and immunology. During this time period these groups produced two compounds in clinical evaluation, an additional three compounds in advanced safety evaluation, a total of twenty-three patents, thirty-two publications, and twenty-six presentations.

The early nineties saw the emergence of high-throughput screening, with the attendant problem of how to sort through the huge amounts of data being generated to find the compounds or series most likely to advance through the development process. He took up this challenge, and with a half dozen or so co-workers developed the objectives necessary to quickly achieve this goal. He published the first description of the Hit-to-Lead process as a stand alone concept in 1996, setting forth the five objectives of Hit-to-Lead that remain valid today, despite the more recent addition of further optional components that can increase the value of this separate phase.

In 1994 he joined Astra, which became AstraZeneca. He was Director of Chemistry at the Rochester, NY site, then at the Worcester, MA site. During the last five years of active employment, he assumed the position of Senior Principal Scientist at the Wilmington, DE site. Here he began to address fundamental questions of small molecule biological activity and selectivity. His work in this area continues with academic collaborators.

Throughout his career he was very active in the external scientific community. As an Associate Professor of Chemistry at the Albany College of Pharmacy he taught medicinal chemistry for seven years. He has served on the editorial advisory board of the Journal of Medicinal Chemistry, and was a section editor for Annual Reports in Medicinal Chemistry. He served on the ACS Medicinal Chemistry Division Long Range Planning Committee, and has organized several meeting symposia. He was Chair of the 1999 Gordon Conference on Medicinal Chemistry, and Co-Chair of the 2002 National Medicinal Chemistry Symposium. He was also Co-Chair of the Conference on New Chemical Technologies Accelerating Drug Discovery, 2001, and served on the Advisory Board for Hit-to-Lead, World Pharmaceutical Congress, 2004.

ACS Division of Medicinal Chemistry

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