After GLIDE docking into the hDAO crystal structure, the surviving compounds were evaluated by the hDAO FEP+ model for potency. Only three top compounds were selected for synthesis, among which compound 66 stood out as a single digit nM hDAO inhibitor on the project. With just one round of synthesis, we were able to confirm that the subpocket is a viable design space to further enhance compound binding potency to the hDAO enzyme, which opens up much needed new SAR space for this target.