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

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1387-1391
    Number of pages5
    JournalBiological and Pharmaceutical Bulletin
    Volume39
    Issue number8
    DOIs
    Publication statusPublished - 2016

    Keywords

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

    ASJC Scopus subject areas

    • Pharmaceutical Science
    • Pharmacology

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