Syntheses of glucose analogues of E5564 as a highly potent anti-sepsis drug candidate.

Glucose analogues 5 and 9 of E5564 were synthesized, and their LPS-antagonistic activities were measured. The inhibitory activities (IC50) on LPS-induced TNFalpha production of these two compounds towards human whole blood cells were 0.06 and 0.83 nM, respectively. Inhibitory doses (ID50) of compounds 5 and 9 on TNFalpha production induced by coinjection of galactosamine and LPS in C3H/HeN mice in vivo were measured and were 0.55 and <0.20 mg/kg, respectively. And also C3H/HeN mice preinjected with compounds 5 and 9 were protected from lethality induced by coinjection of galactosamine and LPS; out of eight mice preinjected with 1 mg/kg of the compounds, one-six and three of eight mice were protected, respectively.