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

doi:10.1016/j.bmc.2006.04.039

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

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	5489-5502
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	14
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2006.04.039
Publication status	Published - Aug 15 2006
Externally published	Yes

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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

Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors : Dual activities and metabolic activation. / Hosoda, Shinnosuke; Tanatani, Aya; Wakabayashi, Ken ichi; Makishima, Makoto; Imai, Keisuke; Miyachi, Hiroyuki; Nagasawa, Kazuo; Hashimoto, Yuichi.

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 16, 15.08.2006, p. 5489-5502.

Research output: Contribution to journal › Article

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10.1016/j.bmc.2006.04.039