Synthesis of Enantiospecific Androgen Receptor Antagonists of Enzalutamide-Resistant Human Prostate Cancer Cells
Drugs targeting the androgen receptor (AR) are important therapeutics for castration-resistant prostate cancer (CRPC) but are vulnerable to resistance due to AR mutations. Previously, we reported that the ( 5R / 5S ) enantiomer pairs of four novel 3-pyrrolazole carboxamide derivatives 9ab – 12ab are antagonists and agonists, respectively, of AR, as demonstrated by transcriptional assays supported by fluorescence microscopy and proliferation studies. Herein, we describe the synthesis and stereochemical characterization of these compounds and document their enantiospecific effect on enzalutamide-resistant AR.
Authors
- Jonathan E. Katz
- Sujatha Chilakala (ORCID: https://orcid.org/0000-0003-1581-3381)
- Charles E. McKenna (ORCID: https://orcid.org/0000-0002-3540-6663)
- David B. Agus (ORCID: https://orcid.org/0000-0002-7499-7822)
- Grzegorz Zapotoczny (ORCID: https://orcid.org/0000-0003-2036-2992)
- B. A. Kashemirov (ORCID: https://orcid.org/0000-0001-7175-9960)
- Katherin Patsch (ORCID: https://orcid.org/0000-0002-8074-9219)
- Pyone Myat Thwe (ORCID: https://orcid.org/0000-0002-6891-5843)
- Elizabeth Elton (ORCID: https://orcid.org/0000-0001-6357-7809)
- Bethany Haliday (ORCID: https://orcid.org/0000-0001-9907-5966)
- Yuanye Sun
- Glenn A. Harter
- Ethan Canfield
- Chao Liu
Institutions
- University of Southern California (US)
- Viterbo University (US)
- California Southern University (US)
- Larry Ellison Foundation (US)
- Keck Graduate Institute (US)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1021/acsmedchemlett.6c00085
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00