Synthesis of Benzimidazole Derivatives as Antiallergic Agents with 5-Lipoxygenase Inhibiting Action.

Abstract

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 Fe³⁺-ADP in rat liver microsomes, in addition to an antagonizing the contraction of guinea pig ileum caused by histamine.