Molecules 2009, 14(2), 785-797; doi:10.3390/molecules14020785
Article

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

1 School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, P.R. China 2 Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, P.R. China
* Authors to whom correspondence should be addressed.
Received: 15 December 2008; in revised form: 18 January 2009 / Accepted: 13 February 2009 / Published: 16 February 2009
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Abstract: The cysteine protease falcipain-2 (FP-2) of Plasmodium falciparum is a principal cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites, making it become an attractive target enzyme for developing anti-malarial drugs. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on compound 1, which was identified by using structure-based virtual screening in conjunction with an enzyme inhibition assay. All compounds showed high inhibitory effect against FP-2 with IC50s of 1.46-11.38 μM, and the inhibitory activity of compound 2a was ~2 times greater than that of prototype compound 1. The preliminary SARs are summarized and should be helpful for future inhibitor design, and the novel scaffold presented here, with its potent inhibitory activity against FP-2, also has potential application in discovery of new anti-malarial drugs.
Keywords: 2-(3; 4-Dihydro-4-oxothieno[2; 3-d]pyrimidin-2-ylthio)acetamide derivatives; Falcipain-2 inhibitor; Malaria; SAR

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

Zhu, Jin; Chen, Tong; Liu, Jie; Ma, Ruoqun; Lu, Weiqiang; Huang, Jin; Li, Honglin; Li, Jian; Jiang, Hualiang. 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.

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