Synthesis and Antiallergic Activity of Novel Azaazulene Derivatives

Abstract

Various azaazulene derivatives were synthesized and their antiallergic activity was examined. The structure-activity relationship among various derivatives modified by introducing substituents at the l-,2-, or 3-position of the azaazulene ring was investigated. The inhibitory activities on allergic histamine release of the compounds bearing a 5-tetrazolyl group at the 3-position were more potent than those of the corresponding compounds with other groups (CN, COOH,and CHO). The compounds substituted with amino, azide and carboxymethylamino groups at the 2-position showed strong inhibitory activity. The compounds with various phenylalkyl groups at the 1-position showed a greater activity than those with other substituents. Among the compounds with substituents at the l-,2-,or 3-position of the azaazulene ring, and (19c) had the most potent inhibitory activities on histamine release from mast cells and on passive cutaneous anaphylaxis (PCA) in rats after oral administration (ED50 = 0.56 and 0.58 mg/kg, respectively). © 1994, The Pharmaceutical Society of Japan. All rights reserved.