Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction

In a continuing effort to discover novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC 50's as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the C8-position not only improved the PDE5 potency but also the isozyme selectivity. Substitutents at the C3-position can incorporate a variety of different groups. The synthesis and primary structure–activity relationship of this new series of potent PDE5 inhibitors are described. The synthesis and primary structure–activity relationship of a new series of potent PDE5 inhibitors is described.