The discovery of potent, selective, and orally bioavailable PDE9 inhibitors as potential hypoglycemic agents

Starting from a non-selective pyrazolo-pyrimidone lead, the sequential use of parallel medicinal chemistry and directed synthesis led to the discovery of potent, highly selective, and orally bioavailable PDE9 inhibitors. The availability of these tools allowed for a thorough evaluation of the therapeutic potential of PDE9 inhibition.

Graphical abstractStarting from the non-selective lead 1, the sequential use of library and directed synthesis led to the optimized PDE9 inhibitor 13.Figure optionsDownload full-size imageDownload as PowerPoint slide