Imidazo[2,1-b]benzothiazoles: II: Synthesis and Antiinflammatory Activity of Some Imidazo[2,1-b]benzothiazoles

3-[2-p-(Un)substituted phenyl]imidazo[2,1-b]benzothiazol-3-yl]propionic acid derivatives (2a—e) were prepared via the interaction of the corresponding 2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazoles (la—e) with acrylic acid in the presence of acetic anhydride and acetic acid. Esterification of 2a—e produced methyl esters (3a—e). Upon the interaction of 3a with m-chloroperbenzoic acid, the 5-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for la—e produced novel [2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3-yl]formaldehyde derivatives (6a—e). Derivatives 6a—e reacted with ethyl bromoacetate to give ethyl 3-hydroxy-3-[2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3-yl]propionate esters (7a—e). Compound dl-7a was resolved with l-(+)-tartaric acid. Compounds 2a—e showed weak or no activity in the carrageenin-induced paw edema assay. Compound 4a significantly inhibited the leakage of pontamine-sky blue dye into the peritoneal cavity of mice, in the capillary permeability inhibition assay. Compound 5a inhibited the writhing by 62 % in the acetic acid-induced writhing assay. © 1989, The Pharmaceutical Society of Japan. All rights reserved.