(3S)-4-[butyl-(2-ethoxy-2-oxoethyl)amino]-3-(naphthalen-2-ylsulfonylamino)-4-oxobutanoic acid | 1027497-14-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3S)-4-[butyl-(2-ethoxy-2-oxoethyl)amino]-3-(naphthalen-2-ylsulfonylamino)-4-oxobutanoic acid
• CAS: 1027497-14-8
• 化学式: C₂₂H₂₈N₂O₇S
• 分子量: 464.54
• InChiKey: IJEAQLRJLIQXJA-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S)-4-[butyl-(2-ethoxy-2-oxoethyl)amino]-3-(naphthalen-2-ylsulfonylamino)-4-oxobutanoic acid 、 (S)-3-(aminomethyl)piperidine-1-carboxamide dihydrochloride 在 N-乙基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 {Butyl-[(S)-3-[((S)-1-carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-amino}-acetic acid ethyl ester; hydrochloride
  参考文献：
  名称：

  Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors

  摘要：

  Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoiminomethyl)piperidine (amidinopiperidine) as a weak, but intrinsically selective, thrombin inhibitor. Elaboration of this molecule provided compounds which inhibit thrombin with K-i's in the range of 20-50 nM and with selectivities of 1000-4000 against trypsin. These inhibitor compounds show a new and unexpected, binding mode to thrombin. Modification of the central building block and then of one of the hydrophobic substituents led to the discovery of a new family of thrombin inhibitors which has reverted td the former binding mode to thrombin. This last class of compounds shows inhibitory activities in the picomolar range; low toxicity; and a short plasma half life which favors its use for an intravenous application. From this series of thrombin;inhibitors, 19f (Ro 46-6240) was selected for clinical development as an antithrombotic agent for intravenous administration.

  DOI：

  10.1021/jm00049a008
• 作为产物：
  描述：

  乙基N-丁基甘氨酸酯 在 N-乙基吗啉 、 盐酸 、 碳酸氢钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.0h， 生成 (3S)-4-[butyl-(2-ethoxy-2-oxoethyl)amino]-3-(naphthalen-2-ylsulfonylamino)-4-oxobutanoic acid
  参考文献：
  名称：

  Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors

  摘要：

  Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoiminomethyl)piperidine (amidinopiperidine) as a weak, but intrinsically selective, thrombin inhibitor. Elaboration of this molecule provided compounds which inhibit thrombin with K-i's in the range of 20-50 nM and with selectivities of 1000-4000 against trypsin. These inhibitor compounds show a new and unexpected, binding mode to thrombin. Modification of the central building block and then of one of the hydrophobic substituents led to the discovery of a new family of thrombin inhibitors which has reverted td the former binding mode to thrombin. This last class of compounds shows inhibitory activities in the picomolar range; low toxicity; and a short plasma half life which favors its use for an intravenous application. From this series of thrombin;inhibitors, 19f (Ro 46-6240) was selected for clinical development as an antithrombotic agent for intravenous administration.

  DOI：

  10.1021/jm00049a008

文献信息

• US5405854A
  申请人：——

  公开号：US5405854A

  公开（公告）日：1995-04-11
• US5578594A
  申请人：——

  公开号：US5578594A

  公开（公告）日：1996-11-26
• US5677448A
  申请人：——

  公开号：US5677448A

  公开（公告）日：1997-10-14
• US5763604A
  申请人：——

  公开号：US5763604A

  公开（公告）日：1998-06-09