Rapid Development and First GMP Manufacture of AMPKγ3 Activator PF-07293893

Organic Process Research & Development 2026

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Authors: Jocelyn L. Baer, Thomas A. Brandt, Adam R. Brown, John M. Curto, Duncan C. Ellinwood, Aran K. Hubbell, Yiyang Liu, John Murray, Giselle P. Reyes, Robert A. Scism, Sergei Tcyrulnikov, Aining Wang
+3 more Ethan S. Weinstein, Gerald A. Weisenburger, Michael G. Vetelino
DOI: 10.1021/acs.oprd.5c00407
Cited by: 0
References: 28

Abstract

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.

Fields of Study & Subjects

Metabolism Diabetes and Cancer Pancreatic function and diabetes Signaling Pathways in Disease

Publication details

Journal / source
Organic Process Research & Development
Volume
30
Issue
1
Pages
189–197
Publication date
2 January 2026
Language
EN