Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib
Abstract
:1. Introduction
2. Results
2.1. Chiral Resolution of Rac-4
2.2. Experimental Chiral Spectroscopy of 4a and 4b
2.2.1. ECD Spectra
2.2.2. ORD
2.2.3. VCD Spectra
2.3. Absolute Configuration Assignment of 4a and 4b
2.3.1. Conformational Analysis of 4
2.3.2. ECD Simulation
2.3.3. SOR and ORD Simulation
2.4. Confirmation of Absolute Configuration Assignment
2.4.1. ECD Derivatization Method
2.4.2. Chemical Correlation Method
2.5. Effect of Configuration on Biological Activity
3. Conclusions
4. Materials and Methods
4.1. General Information
4.2. Computational Section
4.3. Chemical Synthesis
4.3.1. Synthesis of Derivatives 7a/7b
4.3.2. Synthesis of 4a and 4b
4.4. Docking Analysis
4.5. Biological Activity Assays
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compounds | IC50 (nM) |
---|---|
4a ((R)-4) | 2.81 ± 0.32 |
4b ((S)-4) | 0.59 ± 0.10 |
Amuvatinib | 26.89 ± 1.51 |
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Yang, Y.-D.; Zhao, C.; Li, L.-P.; Lv, Y.-X.; Yang, B.-B.; Li, X.; Wang, R.; Li, L. Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib. Pharmaceuticals 2025, 18, 833. https://doi.org/10.3390/ph18060833
Yang Y-D, Zhao C, Li L-P, Lv Y-X, Yang B-B, Li X, Wang R, Li L. Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib. Pharmaceuticals. 2025; 18(6):833. https://doi.org/10.3390/ph18060833
Chicago/Turabian StyleYang, Ya-Dong, Chen Zhao, Liang-Peng Li, Yi-Xin Lv, Bei-Bei Yang, Xin Li, Ru Wang, and Li Li. 2025. "Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib" Pharmaceuticals 18, no. 6: 833. https://doi.org/10.3390/ph18060833
APA StyleYang, Y.-D., Zhao, C., Li, L.-P., Lv, Y.-X., Yang, B.-B., Li, X., Wang, R., & Li, L. (2025). Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib. Pharmaceuticals, 18(6), 833. https://doi.org/10.3390/ph18060833