Synthesis of Tetrasubstituted Phosphorus Analogs of Aspartic Acid as Antiproliferative Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Results
3. Materials and Methods
3.1. Chemistry
3.1.1. General Experimental Information
3.1.2. Compounds Purity Analysis
3.1.3. Experimental Procedures and Characterization Data for Compounds 3, 5, 6, 7, 12, 13, 14 and 18
General Procedure for Synthesis of α-Ketiminophosphonates 3
Procedure for the Synthesis of Ethyl 3-((4-methylphenyl)sulfonamido)-3-phenylpropanoate 5
Procedure for the Synthesis of Diethyl 2-((4-methylphenyl)sulfonamido)-2-phenylsuccinate 6
General Procedure for the Aza-Reformatsky Reaction of α-Ketiminophosphonates 3
Procedure for the Obtention of 3-(Dimethoxyphosphoryl)-3-((4-methylphenyl)sulfonamido)-3-phenylpropanoic acid 14
Procedure for the Obtention of Dimethyl (1-((4-methylphenyl)sulfonamido)-1-phenylethyl)phosphonate 18
3.2. Biology
3.2.1. Materials
3.2.2. Cell Culture
3.2.3. Cytotoxicity 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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Entry | Comp. | R1 | R2 | IC50 (μM) | ||
---|---|---|---|---|---|---|
SKOV3 | A549 | MRC5 | ||||
1 | 5 | CH2CO2Et | H | >50 | 18.68 ± 2.16 | >50 |
2 | 6 | CH2CO2Et | CO2Et | >50 | 14.17 ± 0.41 | >50 |
3 | 7a | CH2CO2Et | P(O)(OMe)2 | >50 | 2.66 ± 0.26 | >50 |
4 | 9a | H | P(O)(OMe)2 | >50 | 17.56 ± 1.3 | >50 |
5 | 18 | CH3 | P(O)(OMe)2 | >50 | >50 | n.d. |
6 | Doxorubicin | 0.13 ± 0.098 | <0.1 | >50 |
Entry | Comp. | R1 | R2 | IC50 (μM) | ||
---|---|---|---|---|---|---|
SKOV3 | A549 | MRC5 | ||||
1 | 7a | Ph | Et | >50 | 2.66 ± 0.26 | >50 |
2 | 7b | 4-Me-C6H4 | Et | >50 | 0.34 ± 0.04 | 29.62 ± 2.98 |
3 | 7c | 3-Me-C6H4 | Et | >50 | 2.00 ± 0.52 | >50 |
4 | 7d | 4-Cl3CS-C6H4 | Et | 6.43 ±0.64 | 4.41 ± 0.29 | 2.47 ± 0.30 |
5 | 7e | 4-Br-C6H4 | Et | >50 | 1.08 ± 0.09 | >50 |
6 | 7f | 4-Cl-C6H4 | Et | 24.12 ± 1.45 | 3.09 ± 0.14 | >50 |
7 | 7g | 3-Cl-C6H4 | Et | >50 | 2.96 ± 0.34 | 38.05 ± 1.61 |
8 | 7h | 3,4-Cl2-C6H3 | Et | 6.94 ± 0.63 | 1.05 ± 0.42 | 11.29 ± 1.16 |
9 | 7i | 3-Cl-4-MeO-C6H3 | Et | >50 | 1.44 ± 0.15 | >50 |
10 | 7j | 4-F-C6H4 | Et | >50 | 7.15 ± 0.24 | >50 |
11 | 7k | 3-F-C6H4 | Et | >50 | 0.59 ± 0.09 | >50 |
12 | 7l | 2-F-C6H4 | Et | >50 | 0.90 ± 0.12 | >50 |
13 | 7m | 2,4-F2-C6H3 | Et | >50 | 2.24 ± 0.31 | >50 |
14 | 7n | 3,4-F2-C6H3 | Et | >50 | 5.70 ± 0.70 | >50 |
15 | 7o | C6F5 | Et | 20.46 ± 2.75 | 3.65 ± 0.21 | >50 |
16 | 7p | 4-CF3-C6H4 | Et | 9.80 ± 0.60 | 20. 30 ± 1.14 | >50 |
17 | 7q | 4-NO2-C6H4 | Et | >50 | 0.67 ± 0.06 | >50 |
18 | 7r | 5-Cl-2-thienyl | Et | 11.77 ± 0.60 | 1.04 ± 0.28 | >50 |
19 | 7s | 4-Ph-C6H4 | Et | 17.01 ± 1.22 | 1.48 ± 0.40 | >50 |
20 | 12 | 3-F-C6H4 | Me | >50 | 24.11 ± 4.01 | n.d. |
21 | 13a | 3-F-C6H4 | Bn | >50 | 12.75 ± 2.38 | n.d. |
22 | 13b | Ph | Bn | >50 | 5.20 ± 0.16 | >50 |
23 | 14 | Ph | H | >50 | 20.61 ± 1.05 | >50 |
24 | Doxorubicin | 0.13 ± 0.098 | <0.1 | >50 |
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del Corte, X.; Maestro, A.; López-Francés, A.; Palacios, F.; Vicario, J. Synthesis of Tetrasubstituted Phosphorus Analogs of Aspartic Acid as Antiproliferative Agents. Molecules 2022, 27, 8024. https://doi.org/10.3390/molecules27228024
del Corte X, Maestro A, López-Francés A, Palacios F, Vicario J. Synthesis of Tetrasubstituted Phosphorus Analogs of Aspartic Acid as Antiproliferative Agents. Molecules. 2022; 27(22):8024. https://doi.org/10.3390/molecules27228024
Chicago/Turabian Styledel Corte, Xabier, Aitor Maestro, Adrián López-Francés, Francisco Palacios, and Javier Vicario. 2022. "Synthesis of Tetrasubstituted Phosphorus Analogs of Aspartic Acid as Antiproliferative Agents" Molecules 27, no. 22: 8024. https://doi.org/10.3390/molecules27228024