Building and Evolving a Chiral Control Strategy for Accelerated COVID Programs
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.
Authors
- Maciej Kalinowski (ORCID: https://orcid.org/0000-0002-6729-1506)
- John J. Salisbury (ORCID: https://orcid.org/0000-0002-3425-248X)
- Hugh J. Clarke (ORCID: https://orcid.org/0000-0003-2626-244X)
- Mengtan Zhang
- Johnny W. Lee (ORCID: https://orcid.org/0000-0002-0950-7815)
- Christophe Allais (ORCID: https://orcid.org/0000-0002-3443-9391)
- Shu Yu (ORCID: https://orcid.org/0009-0008-3328-1028)
- Cuong Manh Duong (ORCID: https://orcid.org/0000-0003-2445-6910)
- Christina G. Connor
- Chintelle James
- Aaron F. Baldwin (ORCID: https://orcid.org/0000-0002-5621-0555)
- Jared L. Piper (ORCID: https://orcid.org/0000-0003-3317-8983)
- Michael Herr (ORCID: https://orcid.org/0000-0001-5614-1820)
- Michael A. Coutant
- R. Matthew Weekly
- John A. Ragan (ORCID: https://orcid.org/0000-0003-4028-3992)
- Yizhou Liu (ORCID: https://orcid.org/0000-0002-1396-922X)
Institutions
- Pfizer (United States) (US)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2024-11-08
- DOI
- https://doi.org/10.1021/acs.oprd.4c00392
- Citations
- 2
- Primary Topic
- SARS-CoV-2 detection and testing
- Type
- article
- Field-Weighted Citation Impact
- 0.78
Funders
- Pfizer