Syntheses of glucose derivatives of E5564-related compounds and their LPS-antagonistic activities.
Glucose analogues 6, 12, 17b, 19a, and 19b of E5564 were synthesized, and their LPS-antagonistic activities were measured. The antagonistic activities (IC(50)) on LPS-induced TNFalpha production of these five compounds toward human whole blood were 72.8, 3.0, 0.9, 7.5, and 1.4nM, respectively. Inhibitory doses (ID(50)) of compounds 12, 17b, 19a, and 19b on TNFalpha 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 0.9mg/kg, respectively.
Shiozaki
Masao
M
Chemistry Department, Chemtech Laboratories, Inc., Hiromachi 1-2-58, Shinagawa-ku, Tokyo 140-8710, Japan. shioza@shina.sankyo.co.jp
Iwano
Yuji
Y
Doi
Hiromi
H
Tanaka
Daisuke
D
Shimozato
Takaichi
T
Kurakata
Shin-ichi
S
D000818:Animals; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005688:Galactosamine / Q000008:administration & dosage / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D006801:Humans; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D005947:Glucose