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 compou nds with good in vivo antiinflammatory activity. Initial efforts led t o a series of alkenes derived from 5,6,7,8-tetrahydroquinolines substi tuted at the 8-position. A second approach concentrated on replacing t he CH linkage of these 8-benzylidene-substituted compounds with other spacer groups and increasing the size of the cycloalkyl ring from a si x- to seven-membered ring, which provided 6,7,8,9-tetrahydro-5H-cycloh epta[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 activ ity after oral administration was found in both the rat carrageenan pa w edema and rat developing adjuvant arthritis models with 2-substitute d 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridines, and of particular inte rest was 27 (WY-28342).