Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action.
Novel benzimidazole derivatives were synthesized and their pharmacological activities were examined. These compounds showed a good suppressive action on histamine release from rat peritoneal mast cells produced by antigen-antibody reaction, an antagonistic action on guinea pig ileum contraction caused by histamine, an inhibitory action on 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and a preventive action on NADPH dependent lipid peroxidation induced by Fe3+-ADP in rat liver microsomes. In addition, 1-[2-[2-(4-Hydroxy-2,3,5-trimethylphenoxy)ethoxy]-ethyl]-2-(4-meth yl-1-homopiperazino)-1H-benzimidazole difumarate (BOM1006) exhibited a dose dependent suppressive action on 48 h homologous passive cutaneous anaphylaxis (PCA) reaction in rats orally administered the drug.
Nakano
H
H
Organic Chemistry Department, Research Laboratories, Fujiyakuhin Co., Ltd., Ohmiya, 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* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016339:Spectrometry, Mass, Fast Atom Bombardment
D018926:Anti-Allergic Agents; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors