Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317. Issue 7 (1st April 2016)

• Record Type: Journal Article
• Authors: Toyama, Hirozumi; Sato, Shoko; Shirakawa, Hitoshi; Komai, Michio; Hashimoto, Yuichi; Fujii, Shinya
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 7(2016)
• Page Start: 1817
• Page End: 1820
• Publication Date: 2016-04-01
• Subjects: Silanol -- Sila-substitution -- Nuclear receptor -- Pregnane X receptor (PXR) -- Retinoic acid receptor-related orphan receptor (ROR) -- T0901317; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.02.031
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We report the design, synthesis, and physicochemical/biological evaluation of novel silanol derivative6 (sila-T) as a silanol analog of multi-target nuclear receptor modulator T0901317 (5 ). Compound6 showed intermediate hydrophobicity between the corresponding alcohol13 and perfluoroalcohol5 . While5 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, silanol6 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.