(RS)-<<1-(aminoiminomethyl)piperidin-3-yl>methyl>carbamic acid tert-butyl ester | 140645-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (RS)-<<1-(aminoiminomethyl)piperidin-3-yl>methyl>carbamic acid tert-butyl ester
• 英文别名: Tert-butyl ({1-[amino(imino)methyl]piperidin-3-yl}methyl)carbamate；tert-butyl N-[(1-carbamimidoylpiperidin-3-yl)methyl]carbamate
• CAS: 140645-13-2
• 化学式: C₁₂H₂₄N₄O₂
• 分子量: 256.348
• InChiKey: IGEJQPQAAYKGLR-UHFFFAOYSA-N

物化性质

• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  91.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (RS)-<<1-(aminoiminomethyl)piperidin-3-yl>methyl>carbamic acid tert-butyl ester 在 N-乙基吗啉 、 盐酸 、 dowex 、 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 反应 4.0h， 生成 (2R)-N-[(1-carbamimidoylpiperidin-3-yl)methyl]-2-(naphthalen-2-ylsulfonylamino)-3-(4-nitrophenyl)propanamide;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：

  N-BOC-3-氨甲基吡啶 在 钌 氢气 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~60.0 ℃ 、10.0 MPa 条件下， 反应 15.0h， 生成 (RS)-<<1-(aminoiminomethyl)piperidin-3-yl>methyl>carbamic acid tert-butyl ester
  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

• [EN] NICOTINAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE NICOTINAMIDE
  申请人：PFIZER LTD

  公开号：WO2009153721A1

  公开（公告）日：2009-12-23

  The present invention relates to compounds of the formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein the substituents are defined herein, to compositions containing such compounds and to the uses of such compounds for the treatment of allergic and respiratory conditions.

  本发明涉及式(I)化合物及其药用可接受的盐和溶剂化物，其中取代基在此处定义，含有此类化合物的组合物，以及使用此类化合物治疗过敏和呼吸系统疾病的用途。
• Nicotinamide Derivatives
  申请人：Crawforth James Michael

  公开号：US20110306597A1

  公开（公告）日：2011-12-15

  The present invention relates to compounds of the formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein the substituents are defined herein, to compositions containing such compounds and to the uses of such compounds for the treatment of allergic and respiratory conditions.

  本发明涉及公式(I)的化合物及其药学上可接受的盐和溶剂，其中取代基在此定义，以及包含这种化合物的组合物，以及这种化合物用于治疗过敏和呼吸系统疾病的用途。
• US5260307A
  申请人：——

  公开号：US5260307A

  公开（公告）日：1993-11-09
• US5532232A
  申请人：——

  公开号：US5532232A

  公开（公告）日：1996-07-02
• US5583133A
  申请人：——

  公开号：US5583133A

  公开（公告）日：1996-12-10