Abstract
Ligands possessing dual vitamin D3 (VD3)-agonistic and androgen-antagonistic activities with various activity spectra were prepared based on a substituted 3,3-diphenylpentane (DPP) skeleton. Among the compounds, (R,S)-DPP-1023 [(R,S)-7b] and (S,S)-DPP-0123 [(S,S)-7c] showed the most potent vitamin D3-agonistic activity [with potency comparable to that of 1α,25-dihydroxyvitamin D3 (1,25-VD3)] and nuclear androgen receptor (AR)-binding activity (with higher affinity than that of hydroxyflutamide), respectively. Metabolic activation (reduction of the carbonyl group) of pivaloyl analogs [DPP-1113 (3a), DPP-1013 (3b), DPP-0113 (3c), and DPP-0013 (3d)] in HL-60 cells was found to be necessary for binding to nuclear vitamin D3 receptor (VDR).
Original language | English |
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Pages (from-to) | 5489-5502 |
Number of pages | 14 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 14 |
Issue number | 16 |
DOIs | |
Publication status | Published - Aug 15 2006 |
Keywords
- Agonist
- Androgen
- Antagonist
- Diphenylpentane
- Metabolism
- Vitamin D
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry