Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317

Hirozumi Toyama, Shoko Sato, Hitoshi Shirakawa, Michio Komai, Yuichi Hashimoto, Shinya Fujii

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    We report the design, synthesis, and physicochemical/biological evaluation of novel silanol derivative 6 (sila-T) as a silanol analog of multi-target nuclear receptor modulator T0901317 (5). Compound 6 showed intermediate hydrophobicity between the corresponding alcohol 13 and perfluoroalcohol 5. While 5 exhibited potent activities toward liver X receptor α and β, farnesoid X receptor, pregnane X receptor (PXR) and retinoic acid receptor-related orphan receptor (ROR)γ, silanol 6 exhibited activity only toward PXR and RORs. Incorporation of silanol instead of perfluoroalcohol is a promising option for developing novel target-selective, biologically active compounds.

    Original languageEnglish
    Pages (from-to)1817-1820
    Number of pages4
    JournalBioorganic and Medicinal Chemistry Letters
    Volume26
    Issue number7
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Nuclear receptor
    • Pregnane X receptor (PXR)
    • Retinoic acid receptor-related orphan receptor (ROR)
    • Sila-substitution
    • Silanol
    • T0901317

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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