Louis J. Lombardo Pages 255 - 268 ( 14 )
The identification and characterization of the multiple isoforms of the phosphodiesterase enzyme has generated considerable interest in the preparation of selective inhibitors of these isozymes. Phosphodiesterase-IV (PDE-IV) is a cyclic AMP-specific phosphodiesterase which has been shown to play an important role in the regulation of inflammatory and immune cell activation. Thus, it has been proposed that selective PDE-IV inhibitors may be useful for the treatment of inflammatory diseases.
A diversity of structural types have been reported as selective PDE-IV inhibitors. Molecular modeling studies have played an important role in the discovery of these agents. An analysis of the structure-activity relationships (SAR) of novel inhibitors and their associated in vitro and in vivo profiles will be discussed.