Rhone-poulenc Rorer Pharmaceuticals Inc.

Gerald M McGeehan

Stevan Wakefield Djuric

Christopher J Burns

Joseph M Salvino

Anthony C Scotese

Kent W Neuenschwander

Robert D Groneberg

Matthew M Morrissette

John W Ullrich

Steven M Condon

This invention is directed to compounds of formula I: ##STR1## wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. Compounds within the scope of the present invention may also inhibit an MMP, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting MMPs, such disease states involve tissue breakdown and those associated with a physiologically detrimental excess of TNF. The present invention is therefore also directed to the pharmaceutical use of the compounds, pharmaceutical compositions containing the compounds, intermediates leading thereto and methods for the preparation of the compounds and their intermediates.

Substituted (aryl, heteroaryl, arylmethyl or heteroarylmethyl)

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Chester Springs, PA, United States of America

Gerald M McGeehan