Nicotinamide derivatives as selective inhibitors of PDE4

Nicotinamide derivatives are claimed as selective inhibitors of phosphodiesterase Type 4 (PDE4) which may be useful for the treatment of inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), pulmonary hypersensitivity, allergic rhinitis, rheumatoid arthritis, psoriasis, and ulcerative colitis, as well as central nervous system (CNS) disorders such as depression and multi-infarct dementia. Certain enantiomers of the present invention are reported to be selective inhibitors of PDE4D, which is the most abundant isozyme in eosinophils. Data included in this application indicate that inhibition of PDE4D results in suppression of both eosinophil activation and degranulation. Such selective inhibitors may be particularly well suited to the treatment of pulmonary inflammatory disorders such as asthma.