Design, synthesis and evaluation of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives as potent inhibitors of platelet aggregation.
Design, synthesis and evaluation of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives as potent inhibitors of platelet aggregation.
复制标题
DOI：
10.1016/j.ejmech.2016.09.032
复制
发表时间：
2017-01
影响因子：
6.7
通讯作者：
Zhouling Xie;Benimana Oscar;Lulu Zhao;Xue Ding;Chen Cao;Sen Feng;Han Li;Chen Pan;Ziyi Bian-Ziyi
中科院分区：
文献类型：
--
作者：
Zhouling Xie;Benimana Oscar;Lulu Zhao;Xue Ding;Chen Cao;Sen Feng;Han Li;Chen Pan;Ziyi Bian-Ziyi
以lx2421为基础，设计、合成了一系列新的2-氨基-3-（萘-2-基）丙酸衍生物，并对其进行了评价。其中，化合物slx14和lx25被认为是有前景的抗血小板聚集药物。他们的微生物学研究表明，lx14可以阻断四种不同诱导剂诱导的血小板聚集，与替罗非班相比，lx14在抑制GPIIb/IIIa受体方面表现出相当的效力。此外，lx14的出血风险比替罗非班低得多，并且在体内显示出显著的抗血栓活性。综上所述，lx14是一种有前景的抗血小板聚集GPIIb/IIIa受体拮抗剂，值得进一步评价。
Based uponLX2421, a previously identified antiplatelet aggregation agent, a series of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives were designed, synthesized and evaluated. Among them, compoundsLX14andLX25were identified as promising antiplatelet aggregation agents. Thein vitrobiologic study demonstrated thatLX14can block platelet aggregation induced by four different inducers and displays comparable potency in inhibiting GPIIb/IIIa receptor in comparison with Tirofiban. In addition,LX14has much lower risk of bleeding than Tirofiban and shows significant antithrombotic activityin vivo. Taking together, the results indicated thatLX14is a promising GPIIb/IIIa receptor antagonist against platelet aggregation worthy of further evaluation.