4-(4-ethylaminophenyl)morpholin-3-one | 1394169-92-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-(4-ethylaminophenyl)morpholin-3-one
• 英文别名: 4-(4-(Ethylamino)phenyl)morpholin-3-one；4-[4-(ethylamino)phenyl]morpholin-3-one
• CAS: 1394169-92-6
• 化学式: C₁₂H₁₆N₂O₂
• 分子量: 220.271
• InChiKey: OFFBFLPNGBWCQX-UHFFFAOYSA-N

物化性质

• 沸点：
  481.0±40.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-ethylaminophenyl)morpholin-3-one 在 4-二甲氨基吡啶 、 10% Pd(OH)₂ on C 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 叔丁醇 为溶剂， 生成 (3S)-N-ethyl-N-[4-(3-oxomorpholin-4-yl)phenyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032
• 作为产物：
  描述：

  4'-溴乙酰苯胺 在 copper(l) iodide 、 lithium aluminium tetrahydride 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 4-(4-ethylaminophenyl)morpholin-3-one
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032

文献信息

• 一种4-(4-氨基苯基)吗啉-3-酮衍生物的制备方法
  申请人：北京鑫开元医药科技有限公司

  公开号：CN111675705A

  公开（公告）日：2020-09-18

  本发明属于药物技术领域，尤其涉及一种4‑(4‑氨基苯基)吗啉‑3‑酮衍生物的制备方法，该方法包括：以4‑(4‑氨基苯基)吗啉‑3‑酮为原料，与第一反应物发生反应，得到第一中间产物；在第一溶剂中，以所述第一中间产物为原料，分批多次加入(S)‑N‑(2,3‑环氧丙基)邻苯二甲酰亚胺在第一温度下发生反应，得到目标产物。此方法通过优化溶剂，使得转化率得到了提高；并使用分批多次的加料方式和后处理方式（浓缩、析晶、过滤、干燥等），获得了较高收率的目标产物，该目标产物为4‑(4‑氨基苯基)吗啉‑3‑酮衍生物，对有效控制利伐沙班的质量有重要意义。
• 一种4-(4-乙胺基苯基)吗啉-3-酮的制备方法及用途
  申请人：北京鑫开元医药科技有限公司

  公开号：CN110372687A

  公开（公告）日：2019-10-25

  本发明属于药物领域，尤其涉及一种4‑(4‑乙胺基苯基)吗啉‑3‑酮的制备方法及用途，该制备方法包括：准备4‑(4‑氨基苯基)吗啉‑3‑酮和乙醛；将所述4‑(4‑氨基苯基)吗啉‑3‑酮和所述乙醛加入反应溶剂中；在所述反应溶剂中加入还原剂进行反应，得4‑(4‑乙胺基苯基)吗啉‑3‑酮。该制备方法以4‑(4‑氨基苯基)吗啉‑3‑酮和乙醛为原料，在还原剂的作用下，在反应溶剂中进行反应，制备方法路线简单，设备条件要求不高，从而可以更为简便、更为安全的制备出4‑(4‑乙胺基苯基)吗啉‑3‑酮，对于有效控制4‑(4‑氨基苯基)吗啉‑3‑酮的质量具有重要意义。