Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

Masashi Takano; Erika Higuchi; Kazunari Higashi; Keisuke Hirano; Akiko Takeuchi; Daisuke Sawada; Atsushi Kittaka

doi:10.3987/COM-14-S(K)108

Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

Masashi Takano, Erika Higuchi, Kazunari Higashi, Keisuke Hirano, Akiko Takeuchi, Daisuke Sawada, Atsushi Kittaka

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Four new 19-norvitamin D₃ analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D₃ were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D₃ showed weak binding affinity for vitamin D receptor (VDR) (2.6% of 1α,25-dihydroxyvitamin D₃: ca. 15% of 1α,25-dihydroxy-19-norvitamin D₃) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC₅₀ 7.3 nM, when 1α,25-dihydroxyvitamin D₃ 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC₅₀ 12.5 nM).

Original language	English
Pages (from-to)	1274-1287
Number of pages	14
Journal	Heterocycles
Volume	90
Issue number	2
DOIs	https://doi.org/10.3987/COM-14-S(K)108
Publication status	Published - 2015
Externally published	Yes

ASJC Scopus subject areas

Analytical Chemistry
Pharmacology
Organic Chemistry

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title = "Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3",

abstract = "Four new 19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 showed weak binding affinity for vitamin D receptor (VDR) (2.6% of 1α,25-dihydroxyvitamin D3: ca. 15% of 1α,25-dihydroxy-19-norvitamin D3) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC50 7.3 nM, when 1α,25-dihydroxyvitamin D3 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC50 12.5 nM).",

author = "Masashi Takano and Erika Higuchi and Kazunari Higashi and Keisuke Hirano and Akiko Takeuchi and Daisuke Sawada and Atsushi Kittaka",

note = "Publisher Copyright: {\textcopyright} 2015 The Japan Institute of Heterocyclic Chemistry.",

year = "2015",

doi = "10.3987/COM-14-S(K)108",

language = "English",

volume = "90",

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T1 - Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

AU - Takano, Masashi

AU - Higuchi, Erika

AU - Higashi, Kazunari

AU - Hirano, Keisuke

AU - Takeuchi, Akiko

AU - Sawada, Daisuke

AU - Kittaka, Atsushi

PY - 2015

Y1 - 2015

N2 - Four new 19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 showed weak binding affinity for vitamin D receptor (VDR) (2.6% of 1α,25-dihydroxyvitamin D3: ca. 15% of 1α,25-dihydroxy-19-norvitamin D3) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC50 7.3 nM, when 1α,25-dihydroxyvitamin D3 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC50 12.5 nM).

AB - Four new 19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 showed weak binding affinity for vitamin D receptor (VDR) (2.6% of 1α,25-dihydroxyvitamin D3: ca. 15% of 1α,25-dihydroxy-19-norvitamin D3) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC50 7.3 nM, when 1α,25-dihydroxyvitamin D3 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC50 12.5 nM).

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Synthesis and preliminary biological evaluation of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

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