A solid-phase approach towards the synthesis of PDE5 inhibitors

PDE5 inhibitors based upon the xanthine scaffold 8 have been expediently synthesized using a solid-phase route. Attachment of the xanthine scaffold 8 using the Rink chloride linker 4 and N-1 functionalization using Mitsunobu chemistry is described. A library of compounds was produced in multi-milligram quantities with excellent purities and acceptable yields. The compounds were tested for their PDE5 inhibitory activity. Synthesis of analogues of xanthine 8 modified at N-1 is described using a practical solid-phase protocol.