ethyl 1-[(2R,15R)-2-[(1-{bis[(tert-butoxy)carbonyl]amino}-4-fluoroisoquinolin-6-yl)amino]-4,15,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[ 14.2.2.1^6,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclopropane-1-carboxylate | 1508297-18-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: ethyl 1-[(2R,15R)-2-[(1-{bis[(tert-butoxy)carbonyl]amino}-4-fluoroisoquinolin-6-yl)amino]-4,15,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[ 14.2.2.1^6,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclopropane-1-carboxylate
• 英文别名: ethyl 1-[(2R,15R)-2-[[1-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-4-fluoroisoquinolin-6-yl]amino]-4,15,17-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclopropane-1-carboxylate
• CAS: 1508297-18-4
• 化学式: C₄₆H₅₄FN₅O₉
• 分子量: 839.961
• InChiKey: WFJJHZWKTVKYLC-WZPDBAAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  61
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  166
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  ethyl 1-[(2R,15R)-2-[(1-{bis[(tert-butoxy)carbonyl]amino}-4-fluoroisoquinolin-6-yl)amino]-4,15,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[ 14.2.2.1^6,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclopropane-1-carboxylate 在 potassium trimethylsilonate 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 18.25h， 生成 US9174974, Example 15
  参考文献：
  名称：

  Synthesis and P1′ SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

  摘要：

  Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.08.088
• 作为产物：
  描述：

  2-溴-5-硝基苯甲醛 在 盐酸 、 N,N-二甲基丙烯基脲 、 copper(l) iodide 、 三(3,6-二氧杂庚基)胺 、 水 、 sodium hydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 氯化铵 、 caesium carbonate 、 三乙胺 、 L-脯氨酸 、 lithium chloride 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 93.5h， 生成 ethyl 1-[(2R,15R)-2-[(1-{bis[(tert-butoxy)carbonyl]amino}-4-fluoroisoquinolin-6-yl)amino]-4,15,20-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[ 14.2.2.1^6,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclopropane-1-carboxylate
  参考文献：
  名称：

  Synthesis and P1′ SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

  摘要：

  Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.08.088

文献信息

• [EN] MACROCYCLIC FACTOR VIIA INHIBITORS<br/>[FR] INHIBITEURS MACROCYCLIQUES DU FACTEUR VIIA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013184734A1

  公开（公告）日：2013-12-12

  The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.

  本发明提供了如规范中定义的Formula (I)的化合物，以及包含任何此类新化合物的组合物。这些化合物是Factor VIIa抑制剂，可用作药物。
• MACROCYCLIC FACTOR VIIA INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150148313A1

  公开（公告）日：2015-05-28

  The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.

  本发明提供了公式（I）的化合物：如规范中定义的和包含任何此类新化合物的组合物。这些化合物是因子VIIa抑制剂，可用作药物。
• US9174974B2
  申请人：——

  公开号：US9174974B2

  公开（公告）日：2015-11-03