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 (1a--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 S-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for 1a--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 carrageein-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.