Christophe Allais, Aaron F. Baldwin, Hugh J. Clarke, Christina G. Connor, Michael Coutant, Cindy Duong, Michael Herr, Chintelle James, Maciej Kalinowski, Johnny W. Lee, Yizhou Liu, Jared L. Piper, John A. Ragan, John J. Salisbury, R. Matthew Weekly, Shu Yu, Mengtan Zhang
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引用次数: 0
Abstract
The development of nirmatrelvir 1 (the active agent in PAXLOVID) was undertaken using a “lightspeed” paradigm to develop an oral antiviral treatment for SARS-CoV-2 (COVID-19). This paper describes our chiral control strategy to deliver high-quality drug substances from first in human studies to an ICH Q3A aligned commercial filing over a period of 17 months. We illustrate our approach to modeling, targeted synthetic efforts, and analytical method development to measure the only two observed stereoisomers instead of the potential 63 in the final drug substance. This paper also provides an overview of how we employed the knowledge gained on chiral control from nirmatrelvir and applied it to our second-generation oral inhibitor, ibuzatrelvir 2.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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