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Arthur A. Patchett, Ph.D.

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 anti-inflammatory agents.

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 sequence.

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 holds.

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 (2001).

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).

ACS Division of Medicinal Chemistry

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