Potent Anthranilic Anilide-Based TRPM4 Channel Inhibitors Identified by a Structure–Activity Relationship Study

-position proved to be favorable for substitutions, where lipophilic groups generally led to more potent inhibitors compared to polar substituents. X-ray structures and NMR studies of anthranilic anilides revealed bifurcated intramolecular hydrogen bonds stabilizing a "bent" conformation that might be important for their mode of action. The discovery of TRPM4 inhibitor PBA, together with other findings from our SAR study, will benefit future TRPM4 drug development efforts and research.