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

抄録

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]banzothiazoles (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 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 inhibiton assay. Compound 5a inhibited the writhing by 62% in the acetic acid-induced writhing assay.