Synthesis and antiinflammatory activity of certain 5,6,7,8-tetrahydroquinolines and related compounds

Modification of some 8-benzylidene-5,6,7,8-tetrahydroquinolines, which have good antiulcer activity, led to three distinct classes of compounds with good in vivo antiinflammatory activity. Initial efforts led to a series of alkenes derived from 5,6,7,8-tetrahydroquinolines substituted at the 8-position. A second approach concentrated on replacing the CH linkage of these 8-benzylidene-substituted compounds with other spacer groups and increasing the size of the cycloalkyl ring from a six- to seven-membered ring, which provided 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine analogues. Finally, the substituent was switched from the cycloalkyl ring to the 2-position of the pyridine ring. Variation of the 2-substituent was also examined. Optimal antiinflammatory activity after oral administration was found in both the rat carrageenan paw edema and rat developing adjuvant arthritis models with 2-substituted 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridines, and of particular interest was 27 (WY-28342).