Synthesis of novel and potent vorapaxar analogues

被引：6
作者：
Knight, Emily [1 ]
Robinson, Eifion [1 ]
Smoktunowicz, Natalia [2 ]
Chambers, Rachel C. [2 ]
Aliev, Abil E. [1 ]
Inglis, Graham G. [3 ]
Chudasama, Vijay [1 ]
Caddick, Stephen [1 ]
机构：
[1] UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England
[2] Ctr Inflammat & Tissue Repair, 5 Univ St, London WC1E 6JJ, England
[3] GSK, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2016年 / 14卷 / 12期
基金：
英国工程与自然科学研究理事会;
关键词：
THROMBIN RECEPTOR ANTAGONIST; PAR-1; ANTAGONISTS; DISCOVERY; RING;
D O I：
10.1039/c5ob02541a
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Vorapaxar is a first-in-class PAR-1 antagonistic drug based on the ent-himbacine scaffold. Detailed in this article are enantioselective and racemic routes to various novel vorapaxar analogues. Biological testing revealed these compounds to have moderate to excellent potencies against PAR-1 with the most potent analogue demonstrating an IC50 of 27 nM.
引用
收藏
页码：3264 / 3274
页数：11
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