(2R)-5-[[amino(nitramido)methylidene]amino]-2-(benzylsulfonylamino)pentanoic acid

• 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: (2R)-5-[[amino(nitramido)methylidene]amino]-2-(benzylsulfonylamino)pentanoic acid
• 化学式: C₁₃H₁₉N₅O₆S
• 分子量: 373.39
• InChiKey: QOPDAAOOAWASIK-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  188
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R)-5-[[amino(nitramido)methylidene]amino]-2-(benzylsulfonylamino)pentanoic acid 在 N-甲基吗啉 、 三甲基铝 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (2R)-N-(2-(((2S)-1-cyclohexyl-3-hydroxy-4-oxo-4-(phenethylamino)butan-2-yl)amino)-2-oxoethyl)-N-methyl-5-((E)-2-nitroguanidino)-2-((phenylmethyl)sulfonamido)pentanamide
  参考文献：
  名称：

  Novel, potent and selective chimeric FXa inhibitors featuring hydrophobic p1-ketoamide moieties

  摘要：

  Judicious combination of P-region sequences of highly potent anticoagulant proteins including NAPS, NAP6, Ecotin, and Antistasin with SAR from small molecule FXa inhibitors led to a series of chimeric inhibitors of formula 1a-j. We report herein the design, synthesis, and biological activity of this novel family of FXa inhibitors that express both high in vitro potency and superb selectivity against related serine proteases. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00458-3
• 作为产物：
  描述：

  在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以100%的产率得到(2R)-5-[[amino(nitramido)methylidene]amino]-2-(benzylsulfonylamino)pentanoic acid
  参考文献：
  名称：

  Novel, potent and selective chimeric FXa inhibitors featuring hydrophobic p1-ketoamide moieties

  摘要：

  Judicious combination of P-region sequences of highly potent anticoagulant proteins including NAPS, NAP6, Ecotin, and Antistasin with SAR from small molecule FXa inhibitors led to a series of chimeric inhibitors of formula 1a-j. We report herein the design, synthesis, and biological activity of this novel family of FXa inhibitors that express both high in vitro potency and superb selectivity against related serine proteases. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00458-3

文献信息

• Identification of the First Low-Molecular-Weight Inhibitors of Matriptase-2
  作者：Mihiret Tekeste Sisay、Torsten Steinmetzer、Marit Stirnberg、Eva Maurer、Maya Hammami、Jürgen Bajorath、Michael Gütschow

  DOI：10.1021/jm100183e

  日期：2010.8.12

  As recently discovered, matriptase-2, a type II transmembrane serine protease, plays a crucial role in body iron homeostasis by down-regulating hepcidin expression, which results in increased iron levels. Thus, matriptase-2 represents a novel target for the development of enzyme inhibitors potentially useful for the treatment of systemic iron overload (hemochromatosis). A comparative three-dimensional model of the catalytic domain of matriptase-2 was generated and utilized for structure-based virtual screening in combination with similarity searching and knowledge-based compound design. Two N-protected dipeptide amides containing a 4-amidinobenzylamide as PI residue (compounds 1 and 3) were identified as the first small molecule inhibitors of matriptase-2 with K-i values of 170 and 460 nM, respectively. An inhibitor of the closely related protease matriptase (compound 2, K-i = 220 nM), with more than 50-fold selectivity over matriptase-2, was also identified.
• Novel, potent and selective chimeric FXa inhibitors featuring hydrophobic p1-ketoamide moieties
  作者：J.Edward Semple、Odile E Levy、Nathaniel K Minami、Timothy D Owens、Daniel V Siev

  DOI：10.1016/s0960-894x(00)00458-3

  日期：2000.10

  Judicious combination of P-region sequences of highly potent anticoagulant proteins including NAPS, NAP6, Ecotin, and Antistasin with SAR from small molecule FXa inhibitors led to a series of chimeric inhibitors of formula 1a-j. We report herein the design, synthesis, and biological activity of this novel family of FXa inhibitors that express both high in vitro potency and superb selectivity against related serine proteases. (C) 2000 Elsevier Science Ltd. All rights reserved.