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

    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

    Fingerprint

    Calcitriol Receptors
    Cholecalciferol
    Inhibitory Concentration 50
    1,25-dihydroxy-19-norvitamin D3

    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

    Cite this

    Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 derivatives and evaluation of their vitamin D receptor-binding affinity. / Biswas, Tanima; Akagi, Yusuke; Usuda, Kosuke; Yasui, Koji; Shimizu, Isao; Okamoto, Mayumi; Uesugi, Motonari; Hosokawa, Seijiro; Nagasawa, Kazuo.

    In: Biological and Pharmaceutical Bulletin, Vol. 39, No. 8, 2016, p. 1387-1391.

    Research output: Contribution to journalArticle

    Biswas, Tanima ; Akagi, Yusuke ; Usuda, Kosuke ; Yasui, Koji ; Shimizu, Isao ; Okamoto, Mayumi ; Uesugi, Motonari ; Hosokawa, Seijiro ; Nagasawa, Kazuo. / Synthesis of 24,24-difluoro-1,3-cis-25-dihydroxy-19-norvitamin D3 derivatives and evaluation of their vitamin D receptor-binding affinity. In: Biological and Pharmaceutical Bulletin. 2016 ; Vol. 39, No. 8. pp. 1387-1391.
    @article{78b0a3549c2d4c23a13748dd3e28e97e,
    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, cis-A ring synthon, Julia-Kocienski coupling, Vitamin D, Vitamin D receptor binding",
    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",
    year = "2016",
    doi = "10.1248/bpb.b16-00316",
    language = "English",
    volume = "39",
    pages = "1387--1391",
    journal = "Biological and Pharmaceutical Bulletin",
    issn = "0918-6158",
    publisher = "Pharmaceutical Society of Japan",
    number = "8",

    }

    TY - JOUR

    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 - cis-A ring synthon

    KW - Julia-Kocienski coupling

    KW - Vitamin D

    KW - Vitamin D receptor binding

    UR - http://www.scopus.com/inward/record.url?scp=84979992185&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84979992185&partnerID=8YFLogxK

    U2 - 10.1248/bpb.b16-00316

    DO - 10.1248/bpb.b16-00316

    M3 - Article

    VL - 39

    SP - 1387

    EP - 1391

    JO - Biological and Pharmaceutical Bulletin

    JF - Biological and Pharmaceutical Bulletin

    SN - 0918-6158

    IS - 8

    ER -