Tumor necrosis factor-t~ (TNF-ct) has been implicated as a key mediator in the progression of rheumatoid arthritis. Inhibitors of phosphodiesterase IV (PDE IV) have been shown to inhibit the production of TNF-ct by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Our efforts in a series ofbiarylcarboxamides have led to the identification of 8j (CP-353,164) as a potent inhibitor of PDE IV and TNF-ot production.