Microwave-Assisted Expeditious Synthesis of 2-Alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines Catalyzed by HgCl2 under Solvent-Free Conditions as Potential Anti-HIV-1 Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Activities
3. Experimental Section
3.1. General Information
3.2. Preparation of 2-Alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines (3a–d′)
3.3. Anti-HIV-1 Activity Assay
3.3.1. Virus and Cells
3.3.2. MTT-Based Cytotoxicity Assay
3.3.3. Syncytia Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of interest
References
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Sample Availability: Samples of the compounds 3a–r′ are available from the authors. |
Entry | Amount of (mmol) | Catalyst (5 mol%) | ta (min) | Isolated Yield b (%) | ||
---|---|---|---|---|---|---|
1a | 2a | 3a | 1a | |||
1 | 0.5 | 1.5 | MgCl2.6H2O | 10 × 3 | 38 | 37 |
2 | 0.5 | 1.5 | ZnCl2 | 10 × 3 | 48 | 23 |
3 | 0.5 | 1.5 | AlCl3 | 10 × 3 | 53 | 9 |
4 | 0.5 | 1.5 | SnCl2.2H2O | 10 × 3 | 63 | 15 |
5 | 0.5 | 1.5 | FeCl3 | 10 × 3 | 68 | 18 |
6 | 0.5 | 1.5 | HgCl2 | 10 × 3 | 91 | 0 |
Entry | Amount of (mmol) | HgCl2 (mol%) | ta (min) | Isolated Yield b (%) | ||
---|---|---|---|---|---|---|
1a | 2a | 3a | 1a | |||
1 | 0.5 | 2.5 | 5 | 10 × 2 | 97 | 0 |
2 | 0.5 | 2.0 | 5 | 10 × 2 | 90 | 0 |
3 | 0.5 | 1.5 | 5 | 10 × 3 | 91 | 0 |
4 | 0.5 | 1.0 | 5 | 10 × 4 | 41 | 55 |
5 | 0.5 | 2.5 | 0 | 10 × 12 | 0 | 100 |
6 | 0.5 | 2.5 | 2.5 | 10 × 5 | 69 | 26 |
7 | 0.5 | 2.5 | 3 | 10 × 3 | 78 | 17 |
8 | 0.5 | 2.5 | 4 | 10 × 3 | 91 | 0 |
9 | 0.5 | 1.5 | 4 | 10 × 3 | 90 | 0 |
3a–d′ | 1 | 2 | tb (min) | Yield c (%) | |||
---|---|---|---|---|---|---|---|
R1 | R2 | R3 | R4 | R5 | |||
3a | H | H | Me | H | Me | 10 × 3 | 90 |
3b | H | p-Me | Me | H | Me | 10 × 3 | 90 |
3c | 6-Me | p-Me | Me | H | Me | 10 × 3 | 95 |
3d | H | p-Cl | Me | H | Me | 10 × 4 | 87 |
3e | 6-Me | p-Cl | Me | H | Me | 10 × 4 | 90 |
3f | H | p-Cl, m-NO2 | Me | H | Me | 10 × 4 | 90 |
3g | 6-Me | p-Cl, m-NO2 | Me | H | Me | 10 × 4 | 89 |
3h | H | m-NO2 | Me | H | Me | 10 × 4 | 85 |
3i | 6-Me | m-NO2 | Me | H | Me | 10 × 4 | 84 |
3j | 5-CN | m-NO2 | Me | H | Me | 10 × 4 | 81 |
3k | 5-CN | p-Me | Me | H | Me | 10 × 4 | 84 |
3l | H | p-OMe | Me | H | Me | 10 × 3 | 90 |
3m | 6-Me | p-OMe | Me | H | Me | 10 × 3 | 93 |
3n | H | p-Me | Et | H | Me | 10 × 3 | 87 |
3o | H | H | n-Pr | H | Me | 10 × 3 | 80 |
3p | H | p-Me | n-Pr | H | Me | 10 × 3 | 86 |
3c | H | p-Cl | Et | H | Me | 10 × 3 | 88 |
3r | H | H | Me | m-Me | Me | 10 × 3 | 84 |
3s | H | p-Me | Me | m-Me | Me | 10 × 3 | 87 |
3t | 6-Me | m-NO2 | Me | H | Et | 10 × 3 | 81 |
3u | H | p-Me | Et | H | Et | 10 × 3 | 88 |
3v | H | p-Me | n-Pr | H | Et | 10 × 3 | 87 |
3w | H | H | Me | m-Me | Et | 10 × 3 | 85 |
3s | 5-NO2 | H | Me | H | Me | 10 × 4 | 90 |
3y | 6-Me | H | Me | H | Me | 10 × 3 | 81 |
3z | 5-CN | H | Me | H | Me | 10 × 4 | 83 |
3a′ | 5-CN | p-Cl | Me | H | Me | 10 × 4 | 80 |
3b′ | 5-NO2 | p-Me | Me | H | Me | 10 × 4 | 87 |
3c′ | 5-NO2 | p-Cl | Me | H | Me | 10 × 4 | 88 |
3d′ | H | H | Et | H | Me | 10 × 3 | 82 |
Entry | Amount of (mmol) | HgCl2 (mol%) | t (min) | Isolated Yield a (%) | |
---|---|---|---|---|---|
1a | 2a | 3a | |||
1 | 3 | 9 | 4 | 5 | 98 |
2 | 3 | 9 | 4 | 6 | 98 |
3 | 3 | 9 | 4 | 8 | 97 |
4 | 3 | 9 | 4 | 9 | 98 |
3s–r′ | CC50 b (μg/mL) | EC50 c (μg/mL) | TI d |
---|---|---|---|
3s | 109.42 | 3.35 | 32.66 |
3y | >200 | 6.12 | >32.68 |
3z | 53.03 | 17.57 | 3.01 |
3a′ | 113 | 3.63 | 31.22 |
3b′ | 132.88 | 9.54 | 13.94 |
3c′ | 53.4 | 6.01 | 8.89 |
3d′ | 105.21 | 20.33 | 5.18 |
3e′ | 15.09 | 15.52 | 0.97 |
3f′ | 43.45 | 1.79 | 24.27 |
3g′ | 80.79 | 22.48 | 3.59 |
3h′ | 4.8 | 3.53 | 1.36 |
3i′ | 20.19 | 0.51 | 39.59 |
3j′ | 2.26 | 12.42 | 0.18 |
3k′ | 16.57 | 19.37 | 0.86 |
3l′ | 181.84 | 57.49 | 3.16 |
3m′ | 12.33 | 22.48 | 0.55 |
3n′ | 11.19 | 16.56 | 0.68 |
3o′ | 151.65 | 18.14 | 8.36 |
3p′ | 134.98 | 63.8 | 2.12 |
3q′ | 78.04 | 3.00 | 26.01 |
3r′ | 98.31 | 4.01 | 24.51 |
AZT e | 1373.17 | 0.00199 | 690,035 |
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Che, Z.; Tian, Y.; Liu, S.; Jiang, J.; Hu, M.; Chen, G. Microwave-Assisted Expeditious Synthesis of 2-Alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines Catalyzed by HgCl2 under Solvent-Free Conditions as Potential Anti-HIV-1 Agents. Molecules 2018, 23, 2936. https://doi.org/10.3390/molecules23112936
Che Z, Tian Y, Liu S, Jiang J, Hu M, Chen G. Microwave-Assisted Expeditious Synthesis of 2-Alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines Catalyzed by HgCl2 under Solvent-Free Conditions as Potential Anti-HIV-1 Agents. Molecules. 2018; 23(11):2936. https://doi.org/10.3390/molecules23112936
Chicago/Turabian StyleChe, Zhiping, Yuee Tian, Shengming Liu, Jia Jiang, Mei Hu, and Genqiang Chen. 2018. "Microwave-Assisted Expeditious Synthesis of 2-Alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines Catalyzed by HgCl2 under Solvent-Free Conditions as Potential Anti-HIV-1 Agents" Molecules 23, no. 11: 2936. https://doi.org/10.3390/molecules23112936