Atomic-level structure of the amorphous drug atuliflapon via NMR crystallography

Holmes, Jacob B.Torodii, DariaBalodis, MartinsCordova, ManuelHofstetter, AlbertParuzzo, FedericoNilsson Lill, Sten O.Eriksson, EmmaBerruyer, Pierrickde Almeida, Bruno SimõesQuayle, MikeNorberg, StefanAnkarberg, Anna SvenskSchantz, StaffanEmsley, Lyndon2025-01-252025-01-252025-01-242024-07-1710.1039/d4fd00078a2-s2.0-85205738186https://infoscience.epfl.ch/handle/20.500.14299/24392339291342We determine the complete atomic-level structure of the amorphous form of the drug atuliflapon, a 5-lipooxygenase activating protein (FLAP) inhibitor, via 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.entrueAtomic-level structure of the amorphous drug atuliflapon via NMR crystallographytext::journal::journal article::research article