Atomic-level structure of the amorphous drug Atuliflapon by NMR crystallography

Abstract

We determine the complete atomic-level structure of the amorphous form of the drug altuliflapon, a 5-lipooxygenase activating protein (FLAP) inhibitor, by chemical shift driven NMR crystallography. The ensemble of preferred structures allows us to identify a number of specific conformations and interactions that stabilize the amorphous structure. These include preferred hydrogen bonding motifs with water and with other drug molecules, as well as conformations of the cyclohexane and pyrazole rings that stabilize structure by indirectly allowing for optimization of hydrogen bonding.