Synthesis of benzimidazole derivatives as antiallergic agents with 5-lipoxygenase inhibiting action.
Syntheses were conducted of novel benzimidazole derivatives that suppress histamine release from mast cells, inhibit 5-lipoxygenase, and possess antioxidative action. Among the compounds synthesized, 1-[2-[2-(4-hydroxy- 2,3,5-trimethylphenoxy)ethoxy]ethyl]-2-(4-methyl-1- homopiperazino)benzimidazole (22) potently suppressed histamine release from rat peritoneal mast cells triggered by the antigen-antibody reaction, inhibited 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and prevented the NADPH-dependent lipid peroxidation induced by Fe(3+)-ADP in rat liver microsomes, in addition to an antagonizing the contraction of guinea pig ileum caused by histamine.
Nakano
H
H
Organic Chemistry Department, Fujiyakuhin Co., Ltd., Saitama, Japan.
Inoue
T
T
Kawasaki
N
N
Miyataka
H
H
Matsumoto
H
H
Taguchi
T
T
Inagaki
N
N
Nagai
H
H
Satoh
T
T
D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
D018926:Anti-Allergic Agents; D001562:Benzimidazoles; D016859:Lipoxygenase Inhibitors