Discovery of a Potent and Orally Bioavailable Zwitterionic Series of Selective Estrogen Receptor Degrader-Antagonists.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
23 02 2023
23 02 2023
Historique:
pubmed:
3
2
2023
medline:
25
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
Herein, we report the optimization of a meta-substituted series of selective estrogen receptor degrader (SERD) antagonists for the treatment of ER+ breast cancer. Structure-based design together with the use of modeling and NMR to favor the bioactive conformation led to a highly potent series of basic SERDs with promising physicochemical properties. Issues with hERG activity resulted in a strategy of zwitterion formation and ultimately in the identification of
Identifiants
pubmed: 36727211
doi: 10.1021/acs.jmedchem.2c01964
doi:
Substances chimiques
Receptors, Estrogen
0
Selective Estrogen Receptor Modulators
0
Estrogen Antagonists
0
Estrogen Receptor alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM