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

Notes

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

著者情報

キーワード: 24,24-difluoro-19-norvitamin D₃, vitamin D receptor binding, cis-A ring synthon, vitamin D, Julia–Kocienski coupling

ジャーナルフリー HTML

2016 年 39 巻 8 号 p. 1387-1391

DOI https://doi.org/10.1248/bpb.b16-00316

詳細

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.

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