Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 derivatives and evaluation of their vitamin D receptor-binding affinity

Tanima Biswas; Yusuke Akagi; Kosuke Usuda; Koji Yasui; Isao Shimizu; Mayumi Okamoto; Motonari Uesugi; Seijiro Hosokawa; Kazuo Nagasawa

doi:10.1248/bpb.b16-00316

Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D₃ derivatives and evaluation of their vitamin D receptor-binding affinity

Tanima Biswas, Yusuke Akagi, Kosuke Usuda, Koji Yasui, Isao Shimizu, Mayumi Okamoto, Motonari Uesugi, Seijiro Hosokawa^*, Kazuo Nagasawa

^*この研究の対応する著者

先進理工学部

研究成果: Article › 査読

7 被引用数 (Scopus)

抄録

Two vitamin D₃ derivatives, namely 24,24-difluoro-1β,3β,25-dihydroxy-19-norvitamin D₃ (6a) and 24,24-difluoro-1α,3α,25-dihydroxy-19-norvitamin D₃ (6b), were synthesized via a convergent route employing Julia-Kocienski olefination as a key step. Compounds 6a and b bound to vitamin D receptor (VDR) with IC₅₀ values of 64.8 and 57.6 nM, respectively, exhibiting about 400- and 30-fold greater binding affinity than the corresponding non-fluorinated derivatives 5a and b.

本文言語	English
ページ（範囲）	1387-1391
ページ数	5
ジャーナル	Biological and Pharmaceutical Bulletin
巻	39
号	8
DOI	https://doi.org/10.1248/bpb.b16-00316
出版ステータス	Published - 2016

ASJC Scopus subject areas

薬理学
薬科学

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10.1248/bpb.b16-00316

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引用スタイル

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title = "Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 derivatives and evaluation of their vitamin D receptor-binding affinity",

abstract = "Two vitamin D3 derivatives, namely 24,24-difluoro-1β,3β,25-dihydroxy-19-norvitamin D3 (6a) and 24,24-difluoro-1α,3α,25-dihydroxy-19-norvitamin D3 (6b), were synthesized via a convergent route employing Julia-Kocienski olefination as a key step. Compounds 6a and b bound to vitamin D receptor (VDR) with IC50 values of 64.8 and 57.6 nM, respectively, exhibiting about 400- and 30-fold greater binding affinity than the corresponding non-fluorinated derivatives 5a and b.",

keywords = "24,24-difluoro-19-norvitamin D, Julia-Kocienski coupling, Vitamin D, Vitamin D receptor binding, cis-A ring synthon",

author = "Tanima Biswas and Yusuke Akagi and Kosuke Usuda and Koji Yasui and Isao Shimizu and Mayumi Okamoto and Motonari Uesugi and Seijiro Hosokawa and Kazuo Nagasawa",

note = "Publisher Copyright: {\textcopyright} 2016 The Pharmaceutical Society of Japan.",

year = "2016",

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language = "English",

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T1 - Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 derivatives and evaluation of their vitamin D receptor-binding affinity

AU - Biswas, Tanima

AU - Akagi, Yusuke

AU - Usuda, Kosuke

AU - Yasui, Koji

AU - Shimizu, Isao

AU - Okamoto, Mayumi

AU - Uesugi, Motonari

AU - Hosokawa, Seijiro

AU - Nagasawa, Kazuo

PY - 2016

Y1 - 2016

N2 - Two vitamin D3 derivatives, namely 24,24-difluoro-1β,3β,25-dihydroxy-19-norvitamin D3 (6a) and 24,24-difluoro-1α,3α,25-dihydroxy-19-norvitamin D3 (6b), were synthesized via a convergent route employing Julia-Kocienski olefination as a key step. Compounds 6a and b bound to vitamin D receptor (VDR) with IC50 values of 64.8 and 57.6 nM, respectively, exhibiting about 400- and 30-fold greater binding affinity than the corresponding non-fluorinated derivatives 5a and b.

AB - Two vitamin D3 derivatives, namely 24,24-difluoro-1β,3β,25-dihydroxy-19-norvitamin D3 (6a) and 24,24-difluoro-1α,3α,25-dihydroxy-19-norvitamin D3 (6b), were synthesized via a convergent route employing Julia-Kocienski olefination as a key step. Compounds 6a and b bound to vitamin D receptor (VDR) with IC50 values of 64.8 and 57.6 nM, respectively, exhibiting about 400- and 30-fold greater binding affinity than the corresponding non-fluorinated derivatives 5a and b.

KW - 24,24-difluoro-19-norvitamin D

KW - Julia-Kocienski coupling

KW - Vitamin D

KW - Vitamin D receptor binding

KW - cis-A ring synthon

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