Dr. Arthur A. Patchett was born on May 28, 1929 in Middletown,
New York. He is a summa cum laude graduate of Princeton in
1951 where he majored in chemistry. He was a Fulbright Scholar
at Cambridge University (1951 – 1952) and his Ph.D.
in chemistry was awarded from Harvard in 1955. His thesis
research on the synthesis of lanostenol was done under the
direction of Prof. R. B. Woodward.
During 1955 – 1957 Patchett did post-doctoral research
with Dr. Bernhard Witkop at the National Institutes of Health.
The syntheses of amino acid analogs and some biochemical mechanism
studies were done during this period. In 1957 he joined the
Merck Research Laboratories working first on analgesics, steroids
and antibacterial agents. He became a director of the Synthetic
Chemistry Department in 1962 and groups under his personal
direction synthesized the anti-inflammatory drug Diflunisal®,
androgen biosynthesis inhibitors and topically active steroidal
In 1972 Dr. Patchett became director of the New Lead Discovery
department. Compounds for biological screening were prepared
by synthesis and from natural product sources. A fermentation
products for screening project supplied extracts of fungi
and Streptomyces whose activity in other programs
suggested they might be producing metabolites worthy of broader
testing. An important and influential discovery of this project
was the HMG-CoA reductase inhibitor Mevacor which became the
first statin drug to be marketed for cholesterol lowering.
Another Merck group added a methyl group to Mevacor® to improve
the metabolic stability of its ester side chain. The resultant
more active product Zocor® became a major product for Merck.
Other research groups have produced the statin drugs Pravachol,
Lipitor® and Crestor® in all cases retaining the active
site functionality of Mevacor®.
The synthesis of enzyme inhibitors was another strategy
of the New Lead Discovery Department. α-Fluoromethyl amino
acids were designed as potent, irreversible decarboxylase
inhibitors which could effectively and specifically inhibit
the formation of histamine and noradrenaline. Phosphinic acids
were mechanism activated, virtually irreversible inhibitors
of a bacterial target D-Ala-D-Ala ligase. Most significant
were the syntheses of the orally active, non-sulphydryl angiotensin
converting enzyme (ACE) inhibitors Vasotec® and Prinivil®. They
had a longer duration of action and less side effects than
the innovative -SH containing ACE inhibitor Capoten®. Vasotec®
and Prinivil® became widely used therapy in the treatment of
hypertension and congestive heart failure.
A second consequential accomplishment of the fermentation
products screening project was the discovery of the cholecystokinin
antagonist asperlicin. Another Merck group increased its potency
by designing much simpler analogs of its benzodiazepine core.
The latter they called a privileged structure and they recommended
that such recurring ligands in G-protein coupled receptors
are a good starting point in the design of agonists and antagonists.
Dr. Patchett’s group developed this idea with the synthesis
of libraries of dipeptides linked to privileged structures.
One of them became the lead for a potent, clinically active
growth hormone secretagogue MK-0677. The same strategy led
to dipeptidyl privileged structure derivatives which are potent
and selective somatostatin and melanocortin MC4 agonists.
Thus the dipeptidyl privileged structure design were shown
to have some generality in generating agonists of much larger
peptides whose message is contained within a reverse turn
In 2002 Dr. Patchett joined the NeoGenesis scientific advisory
board and when they were acquired by Schering-Plough in 2005,
he became one of their consultants, a position which he currently
Dr. Patchett is the co-author of 182 papers and 183 issued
US patents. He was chairman of the ACS Division of Medicinal
Chemistry (1971), was co-chairman of the Drew University Residential
Course in Medicinal Chemistry (1987-2000), and was a member
of the Chemistry Department Advisory Council of Princeton
University (1996-2000). He was a member of the editorial board
of Medicinal Research Reviews (1991-1998). Dr. Patchett was
inducted into the New Jersey Inventors Hall of Fame (1990),
became a fellow of the AAAS (1994) and he received a Doctorate
of Science (hon.) from Bloomfield College (2001). Merck funded
in his honor the Arthur Allan Patchett Professorship at Princeton
Dr. Patchett’s awards include the Merck Directors’
Scientific Award (1987 and 1989), the Pharmaceutical Manufacturers
Association Discoverers’ Award (1992), the American
Chemical Society’s E. B. Hershberg Award (1993), the
Smissman Bristol-Myers Squibb Award (2001), the American Chemical
Society’s Alfred Burger Award in Medicinal Chemistry
(2002) and the National Academy of Sciences Award for Chemistry
in Service to Society (2007).