3-(3-Azabicyclo[2, 2, 1]heptan-2-yl)-1,2,4-oxadiazoles as Novel Potent DPP-4 Inhibitors to Treat T2DM
Abstract
:1. Introduction
2. Results
2.1. Chemical Synthesis
2.2. Molecular Modelling
2.3. X-Ray Diffraction Study
2.4. Inhibitory Activity Assays
3. Discussion
4. Materials and Methods
4.1. Chemical Synthesis
4.2. Molecular Modelling
4.3. Structure and Purity Confirmation
4.4. X-Ray Diffraction Study
4.5. Inhibitory Activity Evaluation
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Structure | GScore (kcal/mol) | LE (kcal/atom) | Lipo (kcal/mol) | ΔG Lipo | ΔG | ΔG Strain |
Trelagliptin | −8.33 | −0.32 | −1.27 | −2.20 | −30.19 | 0.01 |
3a | −6.54 | −0.20 | −2.04 | −8.16 | −29.17 | −4.96 |
3b | −5.85 | −0.18 | −1.35 | −2.68 | −32.96 | −1.19 |
9a | −6.37 | −0.19 | −2.78 | −8.04 | −31.11 | −4.26 |
9b | −6.01 | −0.18 | −1.33 | −2.96 | −29.72 | 2.32 |
Structure | DPP-4 IC50, nM | DPP-8 IC50, nM | DPP-9 IC50, nM |
---|---|---|---|
Neogliptin [13] | 16.8 | >1000 | >1000 |
3a | 21.6 | >1000 | >1000 |
3b | >1000 | >1000 | >1000 |
9a | 4.3 | >1000 | >1000 |
9b | >1000 | >1000 | >1000 |
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Zinevich, T.V.; Maslov, I.O.; Kirichenko, O.G.; Shorshnev, S.V.; Gureev, M.A.; Dolgushin, F.M.; Porozov, Y.B.; Trukhan, V.M. 3-(3-Azabicyclo[2, 2, 1]heptan-2-yl)-1,2,4-oxadiazoles as Novel Potent DPP-4 Inhibitors to Treat T2DM. Pharmaceuticals 2025, 18, 642. https://doi.org/10.3390/ph18050642
Zinevich TV, Maslov IO, Kirichenko OG, Shorshnev SV, Gureev MA, Dolgushin FM, Porozov YB, Trukhan VM. 3-(3-Azabicyclo[2, 2, 1]heptan-2-yl)-1,2,4-oxadiazoles as Novel Potent DPP-4 Inhibitors to Treat T2DM. Pharmaceuticals. 2025; 18(5):642. https://doi.org/10.3390/ph18050642
Chicago/Turabian StyleZinevich, Tatiana V., Ivan O. Maslov, Olga G. Kirichenko, Sergey V. Shorshnev, Maxim A. Gureev, Fedor M. Dolgushin, Yuri B. Porozov, and Vladimir M. Trukhan. 2025. "3-(3-Azabicyclo[2, 2, 1]heptan-2-yl)-1,2,4-oxadiazoles as Novel Potent DPP-4 Inhibitors to Treat T2DM" Pharmaceuticals 18, no. 5: 642. https://doi.org/10.3390/ph18050642
APA StyleZinevich, T. V., Maslov, I. O., Kirichenko, O. G., Shorshnev, S. V., Gureev, M. A., Dolgushin, F. M., Porozov, Y. B., & Trukhan, V. M. (2025). 3-(3-Azabicyclo[2, 2, 1]heptan-2-yl)-1,2,4-oxadiazoles as Novel Potent DPP-4 Inhibitors to Treat T2DM. Pharmaceuticals, 18(5), 642. https://doi.org/10.3390/ph18050642