Synthesis of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as platelet aggregation inhibitors.
Synthesis of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as platelet aggregation inhibitors.
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DOI：
10.1016/j.bmcl.2011.11.027
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发表时间：
2012
影响因子：
2.7
通讯作者：
Xiao Tian;Li-Ying Wang;S. Xia;Zhu-Bo Li;Xinglong Liu;Yuan Yuan-Yuan;Liang Fang;H. Zuo
中科院分区：
文献类型：
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作者：
Xiao Tian;Li-Ying Wang;S. Xia;Zhu-Bo Li;Xinglong Liu;Yuan Yuan-Yuan;Liang Fang;H. Zuo
以3-溴-4-羟基苯甲醛、苯胺和氯乙酰氯为原料，经缩合、还原、O-烷基化和Smiles重排反应合成了2 H-苯并[B][1，4]恶嗪-3（4 H）-酮。所合成的化合物均经核磁共振氢谱、碳谱和高分辨质谱表征，并进行了血小板聚集抑制实验。结果表明，7a-g对ADP诱导的血小板聚集有抑制作用，IC_（50）值为10.14-18.83μmol/L。其中化合物7a的抑制作用最强（IC_（50）=10.14μmol/L），但不及对照药物噻氯匹定（3.18μmol/L）和阿司匹林（6.07μmol/L）。初步研究了该化合物的构效关系。
Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation, reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the synthesized compounds have been characterized by1H NMR,13C NMR, and HRMS, and tested for the inhibitory ability on platelet aggregation. The results have shown that the ADP (adenosine 5′-diphosphate)-induced platelet aggregation was inhibited by 7a–g with the IC50value at 10.14–18.83μmol/L. Compound 7a exhibited the most potent inhibitory effect (IC50=10.14μmol/L) among all the compounds, but less potent than the control drug ticlopidine (3.18μmol/L) and aspirin (6.07μmol/L). The preliminary structure–activity relationship (SAR) was initially investigated in the study.