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Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Identification and optimization of a novel series of [2.2.1]-oxabicyclo imide-based androgen receptor antagonists
Mark E Salvati1, Aaron Balog, Weifang Shan
1Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. mark.salvati@bms.co
Abstract:
A novel series of [2.2.1]-oxabicyclo imide-based compounds were identified as potent antagonists of the androgen receptor. Molecular modeling and iterative drug design were applied to optimize this series. The lead compound [3aS-(3aalpha,4beta,5beta,7beta,7aalpha)]-4-(octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile was shown to have potent in vivo efficacy after oral dosing in the CWR22 human prostate tumor xenograph model.
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