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Development of the Commercial Manufacturing Process for Nirmatrelvir in 17 Months

Christophe Allais, Christina G. Connor, Nga M., Samir A. Kulkarni, Johnny W. Lee, Taegyo Lee, Emma L. McInturff, Jared L. Piper, Dave W. Place, John A. Ragan, R. Matt Weekly

2023ACS Central Science38 citationsDOIOpen Access PDF

Abstract

Nirmatrelvir (PF-07321332, 1) is a selective, orally bioavailable inhibitor of SARS-CoV-2 2 Mpro. Development of an efficient synthesis of this molecule was critical for the rapid advancement of the compound from first synthesis to successful emergency use authorization in just 17 months. This paper provides an overview of the development of the commercial synthesis, with a focus on the supply chains for the three starting materials, which leveraged key synthetic studies from earlier protease research programs and/or commercial products.

Topics & Concepts

AuthorizationKey (lock)Computer scienceProcess managementBusinessManufacturing engineeringCombinatorial chemistryChemistryEngineeringComputer securityComputational Drug Discovery MethodsSynthesis and biological activityInnovative Microfluidic and Catalytic Techniques Innovation
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