Citation: LI Yueqing, WU Qianqian, SONG Qilin, CAO Lei, QIN Qiuyan, XU Yan, ZHAO Weijie. Synthesis and Anti-platelet Aggregation Assay of Cinnamoyl-tyramine Amide Analogues[J]. Chinese Journal of Applied Chemistry, ;2018, 35(10): 1174-1183. doi: 10.11944/j.issn.1000-0518.2018.10.170365 shu

Synthesis and Anti-platelet Aggregation Assay of Cinnamoyl-tyramine Amide Analogues

School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, China

Corresponding author: ZHAO Weijie, zyzhao@dlut.edu.cn
Received Date: 13 October 2017
Revised Date: 13 November 2017
Accepted Date: 18 December 2017

Fund Project: the State Key Development Program for Basic Research of China 2009CB918501Supported by the State Key Development Program for Basic Research of China(No.2009CB918501)

Figures(4)

In order to explore the influence of methoxy substitution in benzene ring, methylation of tyramine hydroxyl and cinnamoyl-tyramine amines, on anti-platelet aggregation activities analogues, cinnamoyl-tyramine amide analogues were synthesized via condensation and methylation with eight benzaldehyde derivatives as raw materials. The structures of synthesized compounds were characterized by nuclear magnetic resonance spectroscopy(NMR), mass spectrometry(MS) and single crystal diffraction. Based on variable-temperature NMR, rotational isomerization based on amide C-N bond was studied for compounds 4a~4h. Their anti-platelet aggregation activities were tested in vitro and assayed by Born test. The results show that nine analogues are more active than podocarpamide. Specifically, compounds 2c, 4c and 4f show inhibition rates of 50.03%, 60.87% and 53.33%, respectively, at 200 μmol/L. The preliminary structure-activity relationship studies on these compounds indicate that 4-methoxy substituent is the most favorable for anti-ADP(adenosine-diphosphate) induced platelet aggregation, and methylated hydroxyl group on ring B and the amide nitrogen also increase the activities to some extent.
- thrombus,
- variable-temperature nuclear magnetic resonance spectroscopy,
- rotational isomerization,
- antiplatelet aggregation
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