A Second-Generation Route to the Cereblon Fragment of ARV-471, Vepdegestrant
A second-generation route to the cereblon fragment of ARV-471, vepdegestrant, an orally available proteolysis targeting chimera (PROTAC) submitted to the FDA for NDA review to treat metastatic breast cancer, is reported. With the new, more convergent route, the chiral cyclic imide moiety is installed as a key fragment via reductive amination with a linker fragment.
Authors
- David J. Bernhardson (ORCID: https://orcid.org/0000-0002-4052-8294)
- Joseph M. Zanghi
- Robert A. Singer (ORCID: https://orcid.org/0000-0001-9730-1261)
- Liam S. Sharninghausen (ORCID: https://orcid.org/0000-0002-2249-1010)
- Johnny W. Lee (ORCID: https://orcid.org/0000-0002-0950-7815)
- Chase A. Salazar (ORCID: https://orcid.org/0000-0002-2221-4865)
- Zebediah C. Girvin (ORCID: https://orcid.org/0000-0001-5338-1319)
- Melissa Lee (ORCID: https://orcid.org/0000-0002-0216-0193)
- Jonathan Fifer
- Ethan S. Weinstein (ORCID: https://orcid.org/0000-0001-8217-9443)
- Gerald A. Weisenburger
- Ryan J. Sullivan (ORCID: https://orcid.org/0000-0001-5540-6962)
- Blake Rauschenberger
- Zheng Wang (ORCID: https://orcid.org/0000-0002-7560-2618)
- Ian Hotham
- Valerie May
Institutions
- Pfizer (United States) (US)
- Lancaster City Council (GB)
- Alphora Research (Canada) (CA)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1021/acs.oprd.5c00271
- Citations
- 3
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 2.42