Design and synthesis of potent PAR-1 antagonists based on vorapaxar
作者: Mengna FanMin HanYan XiaYingbin ZhangYang ChuGuirong BaiWei LiJu LiLihui ZhaoYi HeXiaohui MaZhongyu Duan
作者单位: 1Hebei University of Technology, Tianjin 300100, China
2Tianjin Tasly Academy, Tasly Holding Group Co., Ltd., Tianjin 300410, China
3State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly Holding Group Co., Ltd., Tianjin 300410, China
刊名: Bioorganic & Medicinal Chemistry Letters, 2020, Vol.30 (8)
来源数据库: Elsevier Journal
DOI: 10.1016/j.bmcl.2020.127046
关键词: Vorapaxar analoguesAntiplateletPAR-1 antagonistsStructure-activity relationships
原始语种摘要: Abstract(#br)A series of novel vorapaxar analogues with different amino substitutes at the C-7, C-9a and aromatic substitutes at the C-4 position were designed, synthesized, and evaluated for their inhibitory activity to PAR-1. Several compounds showed good potency in antagonist activity based on the intracellular calcium mobilization assay and excellent pharmacokinetics profile in rats. Among these analogues, 3d exhibited excellent PAR-1 inhibitory activity (IC 50 = 0.18 μM) and the lower ability to cross the blood-brain barrier compared with vorapaxar (IC 50 = 0.25 μM). Compound 3d has the potential to be developed as a new generation of PAR-1 antagonists with a better therapeutic window.
全文获取路径: Elsevier  (合作)
影响因子:2.338 (2012)

  • PAR Page Address Register
  • potent 强大的
  • based 基于
  • synthesis 合成
  • activity 活度