benzyl 4-[2-[(6R,6aR,11bR)-2-cyano-6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolin-6-yl]-5-hydroxy-4-methoxyphenyl]benzoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: benzyl 4-[2-[(6R,6aR,11bR)-2-cyano-6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolin-6-yl]-5-hydroxy-4-methoxyphenyl]benzoate
• 化学式: C₃₈H₃₀N₂O₄
• 分子量: 578.667
• InChiKey: FNJNKILHPALFSB-NZTWMMJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl 4-[2-[(6R,6aR,11bR)-2-cyano-6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolin-6-yl]-5-hydroxy-4-methoxyphenyl]benzoate 在 palladium 10% on activated carbon 、 盐酸羟胺 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 二甲基亚砜 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 生成 (1,1'-Biphenyl)-4-carboxylic acid, 2'-((6R,6aR,11bR)-2-(aminoiminomethyl)-6,6a,7,11b-tetrahydro-5H-indeno(2,1-C)quinolin-6-yl)-5'-hydroxy-4'-methoxy-
  参考文献：
  名称：

  Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor

  摘要：

  A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.013
• 作为产物：
  描述：

  4-羧基苯硼酸 在 indium(III) triflate 、 碳酸氢钠 、 potassium hydrogencarbonate 、 三(邻甲基苯基)磷 、 zinc(II) chloride 作用下， 以 乙二醇二甲醚 、 乙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 26.25h， 生成 benzyl 4-[2-[(6R,6aR,11bR)-2-cyano-6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolin-6-yl]-5-hydroxy-4-methoxyphenyl]benzoate
  参考文献：
  名称：

  Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor

  摘要：

  A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.013

文献信息

• Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor
  作者：E. Scott Priestley、Indawati De Lucca、Jinglan Zhou、Jiacheng Zhou、Eddine Saiah、Robert Stanton、Leslie Robinson、Joseph M. Luettgen、Anzhi Wei、Xiao Wen、Robert M. Knabb、Pancras C. Wong、Ruth R. Wexler

  DOI：10.1016/j.bmcl.2013.02.013

  日期：2013.4

  A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket. (C) 2013 Elsevier Ltd. All rights reserved.