Boc-Asp(OtBu)-N(cPr)Gly-OEt | 155541-32-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-Asp(OtBu)-N(cPr)Gly-OEt
• 英文别名: tert-butyl (3S)-4-[cyclopropyl-(2-ethoxy-2-oxoethyl)amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 155541-32-5
• 化学式: C₂₀H₃₄N₂O₇
• 分子量: 414.499
• InChiKey: QBNYKDIFYGPTLU-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Boc-Asp(OtBu)-N(cPr)Gly-OEt 在 盐酸 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 乙腈 为溶剂， 反应 13.0h， 生成 (S)-N-cyclopropyl-N-ethoxy-carbonylmethyl-3-(2-naphthalenesulfonylamino)-succinamic 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
• 作为产物：
  描述：

  叔丁氧羰基-L-天冬氨酸-4-叔丁酯 、 [(环丙基)氨基]乙酸乙酯 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 Boc-Asp(OtBu)-N(cPr)Gly-OEt
  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

• Neue 1-Amidinopiperidine und 4-Amidinomorphozine als Aggregationshemmer
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0641779A1

  公开（公告）日：1995-03-08

  Die neuen Carboxamide der Formel    worin A,E,G,L,M, R und Q die in der Beschreibung angegebene Bedeutung haben, sowie Hydrate oder Solvate davon hemmen die durch Thrombin induzierte Plättchenaggregation und Gerinnung von Fibrinogen im Plasma. Man kann sie ausgehend von der entsprechenden Säure und dem entsprechenden Amin H₂NCH₂Q herstellen.

  式中的新羧酰胺 其中 A、E、G、L、M、R 和 Q 具有说明中给出的含义，它们及其水合物或溶液可抑制凝血酶诱导的血小板聚集和血浆中纤维蛋白原的凝固。它们可以由相应的酸和相应的胺 H₂NCH₂Q 制备而成。