Inhibitors of PDE4: a review of recent patent literature

The preregistration of roflumilast and the preapproval by the US Food and Drug Administration of cilomilast highlight the continued, albeit slow, progress towards a selective PDE4 inhibitor for the treatment of inflammatory diseases, such as asthma and chronic obstructive pulmonary disease. Whereas the potential therapeutic utility of PDE4 inhibition has been demonstrated in various preclinical animal models (e.g., in rheumatoid arthritis and multiple sclerosis), clinical evaluation has been restricted by dose-limiting side effects, mainly nausea and emesis. Continued disclosure of novel, selective and chemically diverse inhibitors by pharmaceutical companies demonstrates the great interest in PDE4 research. This review focuses on the PDE4 patent literature regarding clinical developments since 2002, and discusses disclosed PDE4 inhibitors from a medicinal chemistry perspective.