Exploration of SAR at other parts of the scaffold may provide openings for improving BBB permeability. The investigation of this scaffold is only at the beginning stages with much yet to learn about the SAR and potentially how the molecules interact with the target intracellularly that could provide further ideas for analog design. Regardless, the pyrazolo-pyrimidine scaffold represents a previously unreported class of AC1 inhibitors that may have potential for treatment or aid in validation of AC1 inhibition as a viable therapeutic strategy for inflammatory pain and to provide alternatives to opioid analgesics.