Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors: Dual activities and metabolic activation

Shinnosuke Hosoda, Aya Tanatani, Ken ichi Wakabayashi, Makoto Makishima, Keisuke Imai, Hiroyuki Miyachi, Kazuo Nagasawa, Yuichi Hashimoto

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39 Citations (Scopus)

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 languageEnglish
Pages (from-to)5489-5502
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number16
DOIs
Publication statusPublished - Aug 15 2006
Externally publishedYes

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Keywords

  • Agonist
  • Androgen
  • Antagonist
  • Diphenylpentane
  • Metabolism
  • Vitamin D

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Hosoda, S., Tanatani, A., Wakabayashi, K. I., Makishima, M., Imai, K., Miyachi, H., Nagasawa, K., & Hashimoto, Y. (2006). Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors: Dual activities and metabolic activation. Bioorganic and Medicinal Chemistry, 14(16), 5489-5502. https://doi.org/10.1016/j.bmc.2006.04.039