These authors contributed equally to this work.
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Communication
Exhaustive Fluorine Scanning toward Potent p53–Mdm2 Antagonists
Article first published online: 27 SEP 2011
DOI: 10.1002/cmdc.201100428
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Huang, Y., Wolf, S., Koes, D., Popowicz, G. M., Camacho, C. J., Holak, T. A. and Dömling, A. (2012), Exhaustive Fluorine Scanning toward Potent p53–Mdm2 Antagonists. ChemMedChem, 7: 49–52. doi: 10.1002/cmdc.201100428
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These authors contributed equally to this work.
Publication History
- Issue published online: 27 DEC 2011
- Article first published online: 27 SEP 2011
- Manuscript Received: 8 SEP 2011
Funded by
- NIH. Grant Numbers: 1R21GM087617-01, 1P41GM094055-01, 1R01GM097082-01
- Qatar Foundation NPRP. Grant Number: 4-319-3-097
- Deutsche Krebshilfe. Grant Number: 108354
Keywords:
- drug discovery;
- fluorine;
- multicomponent reactions;
- p53–mdm2;
- protein–protein interaction
Fluorine dance: We discovered potent p53–Mdm2 antagonists by systematically varying the fluorine substitution pattern around a benzyl group that undergoes stacking interactions with His 96 of Mdm2. The potency of the optimized enantiomer (S)-7 e is >50-fold better than the worst compound of the series. All compounds were efficiently synthesized by Ugi multicomponent reaction chemistry.