Biarylcarboxamide inhibitors of phosphodiesterase IV and tumor necrosis factor-alpha

Tumor necrosis factor-alpha (TNF-alpha) 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-alpha by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Our efforts in a series of biarylcarboxamides have led to the identification of 8j (CP-353,164) as a potent inhibitor of PDE IV and TNF-alpha production. (C) 1997 Elsevier Science Ltd.