2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation
Abstract
:Introduction
Results and Discussion
Identification of Prototype (Hit) 1 by Virtual Screening
Design and Synthesis of Compounds 1-4
Compd. | R1 | R2 | R3 | R4 | Inhibition rate at 10 μM (%) | IC50 (μM) |
1 | H | 88.7 | 2.81 | |||
2a | H | 92.7 | 1.46 | |||
2b | H | 79.0 | 2.05 | |||
2c | H | 85.4 | 2.77 | |||
2d | H | 84.7 | 4.30 | |||
2e | H | 90.6 | 5.74 | |||
3a | —(CH2)4— | 82.2 | 5.77 | |||
3b | H | 85.7 | 2.95 | |||
3c | H | 53.0 | 11.8 | |||
4a | H | 93.3 | 6.63 | |||
4b | H | 94.3 | 5.70 | |||
4c | H | 90.3 | 3.31 | |||
4d | H | 93.2 | 2.49 | |||
4e | H | 72.0 | 5.58 | |||
4f | H | 92.0 | 5.43 |
Enzyme Inhibition Assay
Structure and Activity Relationships
Conclusions
Experimental
Virtual Screening by Molecular Docking
Enzyme Inhibition Assay
General procedures for the preparation of 2-(3,4-dihydro-4-oxothieno[2,3-d]pyrimidin-2-ylthio)-acetamides 1, 2a-e, 3a-c, and 4a-f, exemplified by the preparation of compound 1
Acknowledgements
References
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Zhu, J.; Chen, T.; Liu, J.; Ma, R.; Lu, W.; Huang, J.; Li, H.; Li, J.; Jiang, H. 2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation. Molecules 2009, 14, 785-797. https://doi.org/10.3390/molecules14020785
Zhu J, Chen T, Liu J, Ma R, Lu W, Huang J, Li H, Li J, Jiang H. 2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation. Molecules. 2009; 14(2):785-797. https://doi.org/10.3390/molecules14020785
Chicago/Turabian StyleZhu, Jin, Tong Chen, Jie Liu, Ruoqun Ma, Weiqiang Lu, Jin Huang, Honglin Li, Jian Li, and Hualiang Jiang. 2009. "2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation" Molecules 14, no. 2: 785-797. https://doi.org/10.3390/molecules14020785