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.