Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Kajita, Daisuke; Nakamura, Masaharu; Matsumoto, Yotaro; Ishikawa, Minoru; Hashimoto, Yuichi; Fujii, Shinya
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3350
• Page End: 3354
• Publication Date: 2015-08-15
• Subjects: Sila-substitution -- Silicon -- cis-Olefin mimetic -- Peroxisome proliferator-activated receptor -- PPAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.045
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We recently reported that diphenylsilane structure can function as a cis -stilbene mimetic. Here, we investigate whether silyl functionality can also serve as a mimetic of aliphatic cis -olefin. We designed and synthesized various silyl derivatives of oleoylethanolamide (OEA:8 ), an endogenous cis -olefin-containing PPARα agonist, and evaluated their PPARα/δ/γ agonistic activity. We found that diethylsilyl derivative20 exhibited PPARα/δ agonistic activity, and we also obtained a PPARδ-selective agonist, 32 . Our results suggest that incorporation of silyl functionality is a useful option for structural development of biologically active compounds.