2-[2-(benzyloxy)-5-bromophenyl]-2-hydroxyacetonitrile | 245554-87-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[2-(benzyloxy)-5-bromophenyl]-2-hydroxyacetonitrile
• 英文别名: (2-benzyloxy-5-bromophenyl)-2-hydroxyacetonitrile；2-(5-Bromo-2-phenylmethoxyphenyl)-2-hydroxyacetonitrile
• CAS: 245554-87-4
• 化学式: C₁₅H₁₂BrNO₂
• 分子量: 318.17
• InChiKey: PHMNWJPCUPIPJF-UHFFFAOYSA-N

物化性质

• 沸点：
  495.2±45.0 °C(predicted)
• 密度：
  1.481±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[2-(benzyloxy)-5-bromophenyl]-2-hydroxyacetonitrile 在 盐酸 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 (2-benzyloxy-5-bromophenyl)-2-oxoacetic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Potent and Selective Inhibitors of Blood Coagulation Factor Xa

  摘要：

  Factor Xa (FXa) has materialized as a key enzyme for the intervention of the blood coagulation cascade and for the development of new antithrombotic agents. FXa is the lone enzyme responsible for the production of thrombin and therefore is an attractive target for the control of thrombus formation. We have designed and synthesized a unique series of quinoxalinone FXa inhibitors. This series resulted in 3-{4-[5-((2S,6R)-2,6-dimethylpiperidin-1-yl)pentyl]-3oxo-3,4-dihydroquinoxolin-2-yl}benzamidine (35) with 0.83 nM activity against FXa and excellent selectivity over similar serine proteases. An X-ray crystal structure of compound 35 bound to trypsin along with molecular modeling has led to a predicted binding conformation of compound 35 in FXa. Compound 35 has also been proven to be efficacious in vivo in both the rabbit veno-venous shunt and dog electrolytic injury models. In addition, it was shown that compound 35 did not significantly increase bleeding times in a rabbit model except at the highest doses and plasma concentrations were elevated in a dose dependent manner following a bolus dose and continuous intravenous infusion.

  DOI：

  10.1021/jm0497491
• 作为产物：
  描述：

  2-苄氧基-5-溴苯甲醛 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 2-[2-(benzyloxy)-5-bromophenyl]-2-hydroxyacetonitrile
  参考文献：
  名称：

  Quinoxalinones as serine protease inhibitors such as factor XA and thrombin

  摘要：

  该发明揭示了对丝氨酸蛋白酶如凝血因子Xa、凝血酶和/或凝血因子VIIa具有抑制作用的喹诺酮类化合物。该发明还揭示了这些化合物的药学上可接受的盐和前药，包含这些化合物、它们的盐或前药的药学上可接受的组合物，以及将它们用作治疗或预防哺乳动物中由异常血栓形成特征的疾病状态的方法。

  公开号：

  US06410536B1

文献信息

• Benoxazinones/benzothiazinones as serine protease inhibitors
  申请人：——

  公开号：US20030187256A1

  公开（公告）日：2003-10-02

  This invention discloses benzoxazinone and benzothiazinone compounds which display inhibitory effects on serine proteases such as factor Xa, thrombin, and/or factor VIIa. The invention also discloses pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis.

  本发明揭示了苯并噁嗪和苯并噻嗪化合物，这些化合物对丝氨酸蛋白酶如Xa因子，凝血酶和/或VIIa因子具有抑制作用。本发明还揭示了这些化合物的药学上可接受的盐，包含这些化合物或其盐的药学上可接受的组合物，以及将它们用作治疗或预防哺乳动物异常血栓病状态的治疗剂的方法。
• Quinoxalinones as serine protease inhibitors
  申请人：——

  公开号：US20020086866A1

  公开（公告）日：2002-07-04

  This invention discloses quinoxalinones which display inhibitory effects on serine proteases such as factor Xa, thrombin, and/or factor VIIa. The invention also discloses pharmaceutically acceptable salts and prodrugs of the compounds, pharmaceutically acceptable compositions comprising the compounds, their salts or prodrugs, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis.

  这项发明公开了对丝氨酸蛋白酶（如Xa因子、凝血酶和/或VIIa因子）具有抑制作用的喹诺酮。该发明还公开了该化合物的药物可接受的盐和前药、包含该化合物、其盐或前药的药物可接受的组合物，以及将其作为治疗剂用于治疗或预防哺乳动物的疾病状态，这些状态以异常血栓形成为特征的方法。
• QUINOXALINONES AS SERINE PROTEASE INHIBITORS SUCH AS FACTOR XA AND THROMBIN
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1068190A1

  公开（公告）日：2001-01-17
• BENZOXAZINONES/BENZOTHIAZINONES AS SERINE PROTEASE INHIBITORS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1068191A1

  公开（公告）日：2001-01-17
• US6410536B1
  申请人：——

  公开号：US6410536B1

  公开（公告）日：2002-06-25