Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Design and Synthesis of 8H-Indeno[1,2-d]thiazole Derivatives
2.2. SARS-CoV-2 3CLpro Inhibitory Activities and Structure-Activity Relationships
2.3. Predicting Binding Mode of 7a with 3CLpro
3. Materials and Methods
3.1. Chemistry
3.1.1. General Procedure for the Synthesis of Compounds 7a–7k (Exemplified by 7a)
3.1.2. Procedure for the Synthesis of Compound 7l
3.1.3. General Procedure of Synthesis of 10a–10b (Exemplified by 10a)
3.2. Molecule Docking
3.3. Enzymatic Activity and Inhibition Assays
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Compd. | R1 | R3 | n | SARS-CoV-2 3CLpro | |
---|---|---|---|---|---|
Inhibition (%) at 20 μM | IC50 (μM) | ||||
7a | methoxy | 1 | 89.5 ± 2.0 | 1.28 ± 0.17 | |
7b | butoxy | 1 | 0.5 ± 4.9 | >20 | |
7c | isobutoxy | 1 | −3.1 ± 1.7 | >20 | |
7d | methyl | 1 | 21.7 ± 2.2 | >20 | |
7e | chloro | 1 | 27.2 ± 5.3 | >20 | |
7f | methoxy | 1 | 5.0 ± 5.6 | >20 | |
7g | methoxy | 1 | 32.6 ± 6.8 | >20 | |
7h | methoxy | 1 | 72.5 ± 6.1 | 2.86 ± 0.11 | |
7i | methoxy | 1 | 20.3 ± 4.7 | >20 | |
7j | methoxy | 1 | 31.9 ± 18.2 | >20 | |
7k | methoxy | 1 | 1.5 ± 4.5 | >20 | |
7l | methoxy | 2 | −13.1 ± 1.7 | >20 | |
10a | - | - | 1.9 ± 2.1 | >20 | |
10b | - | - | 1.8 ± 3.5 | >20 | |
PF-07321332 (nirmatrelvir) | 99.5 ± 0.1 | 0.012 ± 0.001 |
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Wu, J.; Feng, B.; Gao, L.-X.; Zhang, C.; Li, J.; Xiang, D.-J.; Zang, Y.; Wang, W.-L. Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors. Molecules 2022, 27, 3359. https://doi.org/10.3390/molecules27103359
Wu J, Feng B, Gao L-X, Zhang C, Li J, Xiang D-J, Zang Y, Wang W-L. Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors. Molecules. 2022; 27(10):3359. https://doi.org/10.3390/molecules27103359
Chicago/Turabian StyleWu, Jing, Bo Feng, Li-Xin Gao, Chun Zhang, Jia Li, Da-Jun Xiang, Yi Zang, and Wen-Long Wang. 2022. "Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors" Molecules 27, no. 10: 3359. https://doi.org/10.3390/molecules27103359
APA StyleWu, J., Feng, B., Gao, L. -X., Zhang, C., Li, J., Xiang, D. -J., Zang, Y., & Wang, W. -L. (2022). Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors. Molecules, 27(10), 3359. https://doi.org/10.3390/molecules27103359