Rapid Development and First GMP Manufacture of AMPKγ3 Activator PF-07293893
We report the development and scale-up of a first-generation route to PF-07293893, an AMPKγ3 activator for the treatment of heart failure. The synthesis includes a metal-catalyzed C–N coupling, a telescoped N-Boc deprotection/amidation sequence, and a final recrystallization. Strategic process optimization addressed key challenges, such as reaction stalling, metal removal, and intermediate instability, ultimately enabling the delivery of over 7.5 kg of API for regulatory toxicological and phase 1 clinical studies.
Authors
- Duncan C. Ellinwood
- Michael G. Vetelino
- Yiyang Liu (ORCID: https://orcid.org/0009-0009-2711-8838)
- John M. Curto (ORCID: https://orcid.org/0000-0001-9033-5952)
- Robert A. Scism
- Thomas A. Brandt (ORCID: https://orcid.org/0000-0003-1998-5789)
- Aining Wang (ORCID: https://orcid.org/0000-0002-2920-1338)
- Giselle P. Reyes
- Aran K. Hubbell (ORCID: https://orcid.org/0000-0001-9087-5553)
- Sergei Tcyrulnikov
- Gerald A. Weisenburger
- Adam R. Brown (ORCID: https://orcid.org/0000-0002-4546-4939)
- Jocelyn L. Baer
- John Murray
- Ethan Weinstein
Institutions
- Pfizer (United States) (US)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2026-01-02
- DOI
- https://doi.org/10.1021/acs.oprd.5c00407
- Primary Topic
- Metabolism, Diabetes, and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00