Syntheses of glucose derivatives of E5564-related compounds and their LPS-antagonistic activities Original Research Article

Glucose analogues 6, 12, 17b, 19a, and 19b of E5564 were synthesized, and their LPS-antagonistic activities were measured. The antagonistic activities (IC50) on LPS-induced TNFα production of these five compounds toward human whole blood were 72.8, 3.0, 0.9, 7.5, and 1.4 nM, respectively. Inhibitory doses (ID50) of compounds 12, 17b, 19a, and 19b on TNFα production induced by co-injection of galactosamine and LPS in C3H/HeN mice in vivo were measured. The values of these compounds were 0.9, ND (not determined), 1.6, and 0.9 mg/kg, respectively.