The Discovery of the Longacting PDE5 Inhibitor PF-489791 for the Treatment of Pulmonary Hypertension - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 169

Figure 8.2 Co-crystal structures of varied PDE5 inhibitors with the PDE5 catalytic
domain, illustrating key interactions and the diversity possible in binding
mode. Solid renderings to PDE5 binding site surface are coloured by
hydrophobicity. (a) Sildenafil with bidentate H-bond to GLN817 and the
ethoxy group located in an orthogonal hydrophobic binding pocket, the
''alkoxy'' pocket. (b) UK-371800, which is ''flipped'' relative to sildenafil
and making H-bonds with both GLN817 and GLN775. The extended
alkoxy group occupies the orthogonal pocket. (c) Tadalafil, H-bonding to
GLN817 and with the methylenedioxyaryl group occupying the ''alkoxy''
pocket. (d) An Eisai phthalazine derivative H-bonding to GLN817 and
with a benzyl group occupying the orthogonal ''alkoxy'' pocket.