MedChemComm
Concise Article
Table 4 Inhibitory activities of target compounds against human FTase
(hFTase)
Municipal Education Commission (grant 13SG32) and the Fok
Ying Tung Education Foundation (141035).
References
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Compound
30a
30b
30c
30d
R1
H
H
OCH3
OH
R2
p-Cl
3,4-Cl2
3,4-Cl2
3,4-Cl2
IC50 (μM)
0.71
0.038
—
Inhibition ratio
77.23
95.99
35.03
−6.52
—
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Conclusions
In this study, a series of pentanedioic acid derivatives as a
kind of novel scaffold farnesyltransferase inhibitors from
lead compounds 6 and 13b were obtained. Some of them
displayed good inhibitory activity. Among them, compound
13n with an IC50 value of 0.0029 μM was the most active one
in this series, which might lead to the discovery of new FTIs.
Chemical modifications of the lead compounds, biological
assays and analysis of the structure–activity relationships
(SAR) were conducted. Some valuable structural optimization
suggestions were obtained to discover more potent FTIs.
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Acknowledgements
This work was supported by the Fundamental Research Funds
for the Central Universities, the National Natural Science
Foundation of China (grants 81102375, 21372078, 81302697,
81222046 and 81230076) (X.L., Z.Z., L.Z., and H.L.), the Shanghai
Committee of Science and Technology (grants 14431902400
and 14431902400) (H.L. and Y. X.), and the 863 Hi-Tech
Program of China (grant 2012AA020308) (H.L.). Honglin Li is
also sponsored by the Shanghai Rising-Star Tracking Program
(grant 13QH1401100), the Innovation Program of Shanghai
17 M. P. Glenn, S.-Y. Chang, C. Hornéy, K. Rivas, K. Yokoyama,
E. E. Pusateri, S. Fletcher, C. G. Cummings, F. S. Buckner,
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