FACILE SYNTHESIS OF (2-BENZIMIDAZOLYL)-1-AZAAZULENES, (2-BENZOTHIAZOLYL)-1-AZAAZULENES, AND RELATED COMPOUNDS AND EVALUATION OF THEIR ANTICANCER IN VITRO ACTIVITY

摘要

Facile syntheses of 2-, 3,- and 8-(2-benzimidazolyl)-1-azaazulenes (2a-c, 5, 7, 9) and 2-, 3-, and 8-(2-benzothiazolyl)-1-azaazulenes (13b-c, 16, 17, 18) were achieved by the condensation of corresponding 1-azaaazulene-carbaldehydes with o-phenylenediamine and 2-aminothiophenol in alcoholic solvents at rt or under reflux under airobic conditions. Reaction of 1-azaazulenecarbaldehyds with 2-aminophenol gave Schiff s bases (10a-c, 11, 12). Reaction of 2-chloro-1-azaazulene-3-carbaldehyde (1a) with 2-aminothiophenol in refluxing 1-BuOH gave benzothiazapine-fused 1-azaazulene (20). Reaction of 4-amino-3-mercapto-4H-1,2,4-triazoles (21a-d) with in refluxing 1-BuOH gave triazolothiadizapine-fused 1-azaazulene (22a-d). The structure of trifluolomethyl derivative (22c) was determined by X-ray structure analysis. 3-(2-Benz- imidazolyl)-2-chloro-1-azaazulene (2a) showed anticancer activity against HeLa S3 cells (IC_(50): 5.3 μM).