The utility of this methodology in a hit-expansion context becomes more evident when observing the four graphs in Figure simultaneously. The [2,5,7] pattern exhibits the highest occurrence, while also demonstrating the greatest variability in terms of pChEMBL value range. This may suggest that either specific functional groups at certain positions contribute more significantly to compound activity, or simply confirms that specific substitution patterns have been explored the most. Conversely, the [2,3,5,7] pattern exhibits the best activity range with very few inactive compounds but as evidenced in Figure , it is underexplored compared to [2,5] and [2,5,7]. By conducting a thorough exploration of these functional groups, it may be possible to cluster active and inactive compounds accordingly to identify the functional groups with a positive impact on compound activity. In conclusion, from the EVP analysis of the adenosine A1 receptor SAR, optimization of target potency could explore and evaluate the design of additional analogs with the [2,3,5,7] pattern, strategically leveraging the EVP that has demonstrated a good overall activity range.