Synthesis of anti -inflammatory α-and β-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4)
摘要:
The low-molecular weight isopropyl 2-acetamido-alpha-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 beta-glucosamine and beta-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-alpha-galactoside 17. (C) 2014 Elsevier Ltd. All rights reserved.
Moenomycin a: spaltung des antibiotikums mit trifluoressigsäure/2-propanol und bestimmung der verknüpfung von d-glucose und 2-acetamido-2-desoxy-d-glucose
SPECIFIC TLR4 ANTAGONIST IN THE TREATMENT OF MULTIPLE MYELOMA
申请人:Etablissement Français du Sang
公开号:US20220023325A1
公开(公告)日:2022-01-27
The present invention relates to a TLR4 (toll-like receptor 4) specific antagonist for use in the treatment of multiple myeloma in a subject suffering from multiple myeloma, and also to an antitumor pharmaceutical combination comprising (i) a TLR4-specific antagonist and (ii) a chemotherapy agent for simultaneous, separate or sequential use in the treatment of multiple myeloma.