Figure 2. Structure activity relationship optimization campaign.

Ten representative compounds, 1 and 3–11, highlight the key steps in the hit-to-lead evolution. The EC₅₀ and relative activity for each compound are shown using the RXFP1 primary screening assay. 100% relative activity was normalized to 57.7 µM forskolin stimulation, and 0% relative activity was normalized to compound vehicle control (0.58% DMSO). Complete concentration-response data are also provided (Supplementary Fig. 1).