Abstract
Abstract The low-molecular weight isopropyl 2-acetamido-α-glucoside 16 (C34) inhibits toll-like receptor 4 (TLR4) in enterocytes and macrophages in vitro, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. We used a copper(II)-mediated solvolysis of anomeric oxazolines and an acid-mediated conversion of β-glucosamine and β-galactosamine pentaacetates to generate analogs of 16 at the anomeric carbon and at C-4 of the pyranose ring. These compounds were evaluated for their influence on TLR4-mediated inflammatory signaling in cultured enterocytes and monocytes. Their efficacy was confirmed using a NF-kB-luciferase reporter mouse, thus establishing the first structure-activity relationship (SAR) study in this series and identifying the more efficacious isopropyl 2-acetamido-α-galactoside 17.
Original language | English (US) |
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Article number | 45432 |
Pages (from-to) | 3097-3100 |
Number of pages | 4 |
Journal | Tetrahedron Letters |
Volume | 56 |
Issue number | 23 |
DOIs | |
State | Published - Jun 3 2015 |
Keywords
- Anti-inflammatory
- Carbohydrates
- Eritoran
- Lipid A mimetics
- Toll-like receptors (TLRs)
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry