This issue of Medicinal Chemistry Research is dedicated to Dr. Nicholas Meanwell on his retirement from Bristol Myers Squibb Co (BMS). Fortunately, this milestone does not mean retirement from activities involving the practice of Medicinal Chemistry, but it does provide a good incentive to celebrate a long and impactful ~ 40-year career with a single organization, albeit one that morphed and merged during that span of time.
Nick received his B.Sc. Special Honours Chemistry from The University of Sheffield, Sheffield, England in 1976. Nick remained at the same university and carried out his Ph.D. work (awarded in 1979) under the supervision of Dr. D. Neville Jones. His thesis was titled “Alkenyl Sulphoxides and Prostanoids” and was the start of his long interest in the chemistry of organosulfur chemistry. The work described in his Ph.D. thesis involves the use of alkenyl sulphoxides as key intermediates in the synthesis of prostaglandin derivatives.
Nick moved to Wayne State University in Detroit for postdoctoral studies where he investigated the synthesis and reactions of sulfoximine derivatives and the synthesis and resolution of natural products, in the labs of Professor Carl R. Johnson. One of us joined the same lab in the fall of 1980 as a first-year graduate student and had the good fortune to know Nick during his postdoctoral stint. As would be expected, Nick enjoyed mentoring by several methods including frequently posing questions about chemistry or literature to the new lab members. However, it was his work ethic that provided the most valuable lessons. Nick would agree that his early training working in his father’s auto repair shop in England, where he learned to find practical solutions efficiently and expeditiously, impacted his approach to organic and later medicinal chemistry. At Wayne State, Nick sought to develop a new methodology with practical applications in the field of organic chemistry. He arrived at the lab early, executed considerable bench chemistry work during the day, organized his bench, and invariably left the lab at a consistent and reasonable hour in time to share dinner with his wife and growing family. In the downtime waiting for reactions, Nick searched the literature, which was hard copy journals at the time, for “useful” advances. His efforts at Wayne State resulted in a general synthetic approach to sulfoximine derivatives via sulfonimidoyl fluorides, the first synthesis of that class. Utilizing a versatile common intermediate, he also designed and completed syntheses of hop ether, cis-jasmone, sarkomycin, and known synthetic precursors to 11-deoxy-prostaglandins and PGE2. He designed and realized a synthesis of the ginseng constituent β-panasinsene that was resolved via a kinetic resolution using sulfoximine chemistry. Nick’s noteworthy efficiency at the bench continued in his industrial career. He frequently found a way to rapidly advance the SAR via synthetically accessible targets that usually provided crystalline intermediates or readily isolable final products.
Nick joined the Bristol Myers Pharmaceutical Research and Development Division, as a research scientist at their Mead Johnson site in Evansville, Indiana, in August 1982. In 1987, Bristol Myers Pharmaceutical Research and Development Division consolidated their preclinical drug discovery research in Wallingford, CT where Nick worked until the site closed in 2018. He then relocated to their site in Princeton, NJ rising to the level of Vice President/Scientific Vice President, until his retirement in October 2022. During that time, the BMS preclinical research organization merged, in chronological order, with those from E.R. Squibb, Dupont-Merck Pharma, and Celgene. Nick’s medicinal chemistry research at BMS was in the therapeutic areas of cardiovascular, central nervous system, virology, and immunology. Nick is particularly well known for his leadership as executive director of virology chemistry at a time when the entire virology organization realized a high level of productivity and provided considerable advances in the areas of HCV and HIV therapeutics. These efforts produced marketed HCV NS5A inhibitor, daclatasvir, the NS3/4A protease inhibitor, asunaprevir, and the NS5B allosteric inhibitor, beclabuvir and the HIV attachment inhibitor fostemsavir currently marketed by ViiV Healthcare as Rukobia®. Nick’s career has to date resulted in co-authorship on ~206 peer-reviewed publications. Those who are co-authors with Nick on one or more of these publications will attest to his high standards, demand for critical thinking, and the rigorous editing of manuscripts. Nick is a co-inventor on ~144 granted U.S. patents which is a valid indication of his effectiveness and creativity as a practicing medicinal chemist. Further confirmation of his considerable impact is provided by the fact that Nick has been a member or a leader of teams that have produced 33 different clinically evaluated compounds. A companion article in this journal’s special issue authored by Nick provides details of his involvement in these discoveries and the collaborators with whom he was associated. As a result of his significant scientific contributions which had an impact on the well-being of society, Nick has received a number of awards and recognition. These include: Elected as a Fellow of the Royal Society of Chemistry, October 1999; Elected as a Member, Connecticut Academy of Science and Engineering, February 2014; Co-recipient of the 2014 Research and Hope Award for Excellence in Biopharmaceutical Industry Research sponsored by the Pharmaceutical Research and Manufacturers of America (PhRMA) for the HIV-1 Attachment Inhibitor program, September 2014; Recipient of the 2015 Philip S. Portoghese Journal of Medicinal Chemistry/American Chemical Society (ACS) Division of Medicinal Chemistry (MEDI) Joint Lectureship Award; Inducted into the ACS MEDI Hall of Fame, August, 2015; Co-recipient of a 2017 “Heroes of Chemistry” Award sponsored by the ACS; Recipient of the 2022 ACS Alfred Burger Award in Medicinal Chemistry; Elected as an ACS Fellow, August 2022.
The granting of some of these awards was undoubtedly influenced by Nick’s efforts to educate and promote excellence in the practice of medicinal chemistry. Nick has been a co-author or sole author on 27 book chapters or books and on ~58 reviews which include overviews of progress in specific areas of research, summaries of important compounds, various important drug design concepts such as fluorine chemistry, bioisosterism, toxicophores, heterocycles, prodrugs, efficiency metrics, etc. He has written editorials, editorial comments, and reviews of other publications. Nick’s service to the field of medicinal chemistry and as an educator has been extensive and extends far beyond his published work and Bristol Myers Squibb. It includes numerous invited lectures at meetings and academic institutions, medicinal chemistry courses, service to professional organizations such as the ACS, as a session chair, session organizer, as a member of MEDI long-range planning committees, as well as serving on editorial boards of various journals. He was the Perspectives Editor for the Journal of Medicinal Chemistry from mid-2017-2022 and is currently an Associate Editor for the Journal.
All these accomplishments could not have been possible were it not for Nick’s genuine passion for chemistry and drug discovery and his enthusiasm for enhancing and promoting its practice and excellence. He is truly an example of someone who took the advice of selecting a career that he loved and who has achieved excellence in its pursuit. Outside of medicinal chemistry and drug discovery, Nick’s other passions are bicycling and photography, which provide him with the required physical and mental diversions to recharge. In addition, Nick is an effective bicycle mechanic. Finally, and most importantly, the one other constant in Nick’s life is his family which includes his supportive wife Pat and their two children Emily and Steven.
While a list of Nick’s past positions is too extensive for an editorial, some of the positions he currently holds are: Principal, NuArq MedChem Consulting, November 2022–present; Distinguished Professor, The Baruch S. Blumberg Institute, January 2023–present; Adjunct Professor of Medicinal Chemistry, College of Pharmacy, The University of Michigan, April 2023–present; Member, American Chemical Society MEDI Division Long Range Planning Committee, 2023–2025, formulating the MEDI program for the two annual ACS National Meetings (the second of such terms); Member U19 Scientific Advisory Committee for CETR New World Alphaviruses, March 2019–present; Member, Scientific Advisory Board, Cleveland Clinic Center for Therapeutics Discovery, January 2020–present; Member, Scientific Advisory Board, Fox Chase Chemical Diversity Center, Pennsylvania Biotechnology Center, January 2020–present; Member, Scientific Advisory Board, Midwest AViDD Center, October 2022–present; Member, Scientific Advisory Board, Institute for Therapeutics Discovery and Development, The University of Minnesota, January 2023–present.
Nick’s love and curiosity for chemistry and science in general is infectious. He has inspired a generation of medicinal chemists to learn broadly and deeply on all aspects of drug discovery, at the same time not to be limited by conventional thinking in drug design but to think creatively. While Nick’s mentorship, scholarship, and knowledge sharing are dearly missed by many of his former colleagues at BMS, the medicinal chemistry and drug discovery community is heartened by the fact that he has decided to continue his passion for medicinal chemistry and in the process, have a positive impact on the next generation of leaders in drug discovery. We can hardly wait to read the next review or publication or hear a lecture from Nick and wish him continued success and impact as he moves into a new phase of his evolving career.
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Kadow, J.F., Yeung, KS. & Murali Dhar, T.G. Special issue of Medicinal Chemistry Research in honor of Dr. Nicholas A. Meanwell. Med Chem Res 32, 1205–1207 (2023). https://doi.org/10.1007/s00044-023-03098-8