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 journalArticle

9 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 Jan 1

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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