An update on cyclic nucleotide phosphodiesterase (PDE) inhibitors: phosphodiesterases and drug selectivity

In recent years, there has been a prodigious expansion of knowledge about cyclic nucleotide phosphodiesterases (PDEs). This isozyme superfamily has now become a major focus of drug discovery efforts owing to its diversity, molecular nature, differential regulation and expression in different cell types, and the range of biological functions. Inhibition of these isozymes can lead to an increase in cAMP and cGMP levels, which can affect a variety of physiological responses. Selective inhibitors for each of the multiple forms of PDE can offer an opportunity for desired therapeutic intervention and would be an extremely useful tool in drug discovery efforts for a medicinal chemist. This review details many key aspects of multiple forms of PDEs and their inhibitors with diversified chemical structures, which can act as leads for synthesis of novel drugs.