Rhodanine derivatives as novel inhibitors of PDE4

The discovery, synthesis and in vitro activity of a novel series of rhodanine based phosphodiesterase-4 (PDE4) inhibitors is described. Structure-activity relationship studies directed toward improving potency led to the development of submicromolar inhibitors 2n and 3i (IC50 = 0.89 & 0.74 μM). The replacement of rhodanine with structurally related heterocycles was also investigated and led to the synthesis of pseudothiohydantoin 7 (IC50 = 0.31 μM).

Graphical abstractThe discovery, synthesis and in-vitro activity of a novel series of rhodanine based phosphodiesterase-4 inhibitors (e.g. 3i) is described.Figure optionsDownload full-size imageDownload as PowerPoint slide