SYNTHESIS AND ANTIINFLAMMATORY ACTIVITY OF CIS AND TRANS-6,6A,7,8,9,10,10A,11-OCTAHYDRO-11-OXODIBENZO[B,E]THIEPINACETIC AND OXEPINACETIC ACIDS

A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochemical feature (C6a, C10a, and C2'). The 6a,10a-trans compounds exhibited considerable antiinflammatory activity, whereas the 6a,10a-cis compounds were inactive. Among the trans compounds, 6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thie-pin-3-propionic acid (9a) and its oxepin analogue (13a) showed an antiinflammatory activity superior to that of indomethacin. The phenethyl ester (25) of 9a showed potent antiinflammatory activity, and its safety index (UD50/ED50) was over 14 times higher than that of indomethacin. The phenethyl ester (25) is the most favorable compound with high antiinflammatory activity and little ulcerogenicity. © 1990, American Chemical Society. All rights reserved.