2. Academic Validation
  3. Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317

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

  • Bioorg Med Chem Lett. 2016 Apr 1;26(7):1817-20. doi: 10.1016/j.bmcl.2016.02.031.
Hirozumi Toyama 1,  Shoko Sato 2,  Hitoshi Shirakawa 3,  Michio Komai 3,  Yuichi Hashimoto 1,  Shinya Fujii 1
Affiliations

Affiliations

  • 1 Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032 Tokyo, Japan.
  • 2 Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
  • 3 Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan.
PMID: 26905831 DOI: 10.1016/j.bmcl.2016.02.031
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.

Keywords

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

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