Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
AMR | X | Y | Cpd | Y′ | R | Yield (%) |
---|---|---|---|---|---|---|
I | CN | CN | 1 [43] | NH2 | Me | 56 |
II | CN | COC(Me)3 | 2 | t-Bu | Me | 61 |
III | CN | COPh | 3 | Ph | Me | 60 |
III | CN | COPh | 4 | Ph | CH2Ph | 27 |
IV | COPh | COPh | 5 | Ph | Me | 50 |
V | COOMe | CN | 6 | NH2 | Me | 12 |
VI | SO2Ph | CN | 7 | NH2 | Me | 61 |
2.2. NMR and Mass Spectrometry Analyses of Derivatives 8a and 8b
2.3. Antiproliferative Activity
3. Materials and Methods
3.1. Chemistry
3.2. General Synthetic Procedure for the Preparation of Pyrazoles 1–7
3.3. Synthesis of Ethyl 2-Cyano-3-(methylthio)-3-(phenylamino)acrylate (BVI)
3.4. Synthesis of Compounds 8a and 8b
3.5. Synthesis of Compound 8b via Pyrazole Methylation
3.6. Mass Spectrometry Analysis
3.6.1. LC-HRMS
3.6.2. FIA MS/MS
3.6.3. Biology
3.7. Computational Calculations
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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Cpd | Mean Growth Percentage ± SD | ||||||||
---|---|---|---|---|---|---|---|---|---|
MCF7 | MDA-MB231 | Sk-Br3 | SKMEL28 | SKOV3 | Hep-G2 | HeLa | A549 | GM-6114 | |
1 | 108.43 ± 7.38 | 113.77 ± 4.39 | 92.72 ± 2.94 | 91.62 ± 3.38 | 107.78 ± 3.35 | 105.55 ± 7.40 | 97.39 ± 10.47 | 111.66 ± 3.77 | 89.08 ± 11.38 |
2 | 107.37 ± 10.99 | 112.16 ± 6.85 | 85.66 ± 3.28 | 92.87 ± 4.06 | 107.12 ± 5.64 | 94.15 ± 3.81 | 96.42 ± 7.05 | 113.10 ± 5.64 | 90.65 ± 3.32 |
3 | 118.46 ± 6.19 | 115.98 ± 2.45 | 83.05 ± 2.41 | 92.97 ± 3.68 | 115.25 ± 3.37 | 112.20 ± 7.47 | 110.40 ± 2.49 | 115.25 ± 5.96 | 109.73 ± 8.12 |
4 | 92.21 ± 5.41 | 89.69 ± 2.90 | 84.72 ± 4.38 | 68.36 ± 3.13 | 80.45 ± 3.38 | 105.51 ± 8.80 | 73.77 ± 6.86 | 71.00 ± 3.40 | 83.00 ± 6.51 |
5 | 111.88 ± 5.19 | 111.89 ± 2.95 | 101.95 ± 3.18 | 119.57 ± 1.57 | 105.35 ± 6.08 | 110.03 ± 2.11 | 115.87 ± 9.17 | 112.22 ± 4.10 | 102.18 ± 8.31 |
6 | 105.46 ± 5.68 | 109.32 ± 6.43 | 81.74 ± 4.92 | 105.04 ± 2.76 | 109.12 ± 5.64 | 102.04 ± 4.42 | 92.32 ± 2.62 | 121.90 ± 5.92 | 84.57 ± 4.03 |
7 | 104.20 ± 3.10 | 110.14 ± 4.88 | 89.26 ± 3.54 | 109.99 ± 3.30 | 106.54 ± 4.47 | 107.16 ± 12.07 | 85.42 ± 6.98 | 115.77 ± 3.02 | 87.45 ± 7.73 |
8a | 98.06 ± 3.31 | 87.02 ± 5.76 | 94.76 ± 4.00 | 82.21 ± 4.00 | 106.46 ± 6.18 | 101.20 ± 9.16 | 103.26 ± 9.57 | 99.70 ± 9.20 | 107.65 ± 3.92 |
8b | 100.13 ± 6.20 | 89.99 ± 5.16 | 100.28 ± 4.10 | 81.21 ± 4.31 | 102.97 ± 4.37 | 98.37 ± 8.17 | 110.61 ± 7.72 | 86.65 ± 9.83 | 118.99 ± 9.70 |
cisplatin | 72.74 ± 5.48 | 86.07 ± 7.04 | 70.59 ± 3.83 | 44.40 ± 2.53 | 36.83 ± 4.35 | 38.07 ± 2.22 | 29.33 ± 2.23 | 59.09 ± 6.03 | 39.52 ± 2.74 |
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Lusardi, M.; Profumo, A.; Rotolo, C.; Iervasi, E.; Rosano, C.; Spallarossa, A.; Ponassi, M. Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives. Molecules 2022, 27, 5814. https://doi.org/10.3390/molecules27185814
Lusardi M, Profumo A, Rotolo C, Iervasi E, Rosano C, Spallarossa A, Ponassi M. Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives. Molecules. 2022; 27(18):5814. https://doi.org/10.3390/molecules27185814
Chicago/Turabian StyleLusardi, Matteo, Aldo Profumo, Chiara Rotolo, Erika Iervasi, Camillo Rosano, Andrea Spallarossa, and Marco Ponassi. 2022. "Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives" Molecules 27, no. 18: 5814. https://doi.org/10.3390/molecules27185814