materialscloud:2025.22
Published January 28, 2025 | Version v1
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Atomic-level structure of the amorphous drug Atuliflapon via NMR crystallography

Creators

  • 1. Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
  • 2. National Centre for Computational Design and Discovery of Novel Materials MARVEL, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
  • 3. Data Science & Modelling, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden
  • 4. Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden.

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Description

We 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.

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References

Journal reference (Paper with previously published which contains NMR data, MD simulations, and crystalline assignment)
Cordova, M., Balodis, M., Hofstetter, A., Paruzzo, F., Nilsson Lill, S. O., Eriksson, E. S. E., Berruyer, P., Simões de Almeida, B., Quayle, M. J., Norberg, S. T., Svensk Ankarberg, A., Schantz, S., & Emsley, L. Nature communications, 12(1), 2964. (2021)., doi: 10.1038/s41467-021-23208-7

Journal reference (External reference to the paper)
J. Holmes, D. Torodii, M. Balodis, M. Cordova, A. Hofstetter, F. Paruzzo, S. Nilsson Lill, P. Berruyer, B. Simoes de Almeida, M. Quayle, S. Norberg, A. Ankarberg, S. Schantz, L. Emsley, Faraday Discuss, 255 , 342-354, 2025, doi: 10.1039/d4fd00078a

Journal reference (External reference to the paper)
J. Holmes, D. Torodii, M. Balodis, M. Cordova, A. Hofstetter, F. Paruzzo, S. Nilsson Lill, P. Berruyer, B. Simoes de Almeida, M. Quayle, S. Norberg, A. Ankarberg, S. Schantz, L. Emsley, Faraday Discuss, 255 , 342-354, 2025