(RS)-4-aminobutane-1,2-diol hydrochloride | 87681-47-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (RS)-4-aminobutane-1,2-diol hydrochloride
• 英文别名: 1,2-Butanediol, 4-amino-, hydrochloride；4-aminobutane-1,2-diol;hydrochloride
• CAS: 87681-47-8
• 化学式: C₄H₁₁NO₂*ClH
• 分子量: 141.598
• InChiKey: DRZGKLVLGVETGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.89
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  66.5
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-氟-4-碘苯胺)-3,4-二氟苯甲酸 、 (RS)-4-aminobutane-1,2-diol hydrochloride 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3,4-dihydroxybutyl)-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamide
  参考文献：
  名称：

  Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)

  摘要：

  The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and is constitutively activated or highly upregulated in many tumor types. Mutations associated with upstream pathway components RAS and Raf occur frequently and contribute to the oncogenic phenotype through activation of MEK and then ERK. Inhibitors of MEK have been shown to effectively block upregulated ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated early evidence of efficacy in the clinic for the treatment of cancer. Guided by structural insight, a strategy aimed at the identification of an optimal diphenylamine-based MEK inhibitor with an improved metabolism and safety profile versus PD-0325901 led to the discovery of development candidate 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo in preclinical models with sustained duration of action and is currently in early stage clinical trials. potency and efficacy in preclinical models with sustained duration of action and is currently in early stage clinical trials.

  DOI：

  10.1021/ml300049d
• 作为产物：
  描述：

  (RS)-4-bis(tert-butoxycarbonyl)aminobutane-1,2-diol 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以96%的产率得到(RS)-4-aminobutane-1,2-diol hydrochloride
  参考文献：
  名称：

  Stability of Boronic Esters to Hydrolysis: A Comparative Study

  摘要：

  硼酸酯是合成生物活性化合物（如凝血酶和蛋白酶体抑制剂）的关键中间体。然而，它们在合成反应过程中以及在生物介质中均表现出较低的水解稳定性。我们报道了多种硼酸酯的制备及其与相应的水解稳定性较高的二氢二醇硼酸酯的稳定性对比研究。我们发现，由(1,1′-双环己基)-1,1′-二醇衍生的硼酸酯在所研究的样品中水解稳定性最高。

  DOI：

  10.1246/cl.2009.750

文献信息

• Stability of Boronic Esters to Hydrolysis: A Comparative Study
  作者：Raffaella Bernardini、Ambrogio Oliva、Alessandro Paganelli、Ernesto Menta、Mario Grugni、Sergio De Munari、Luca Goldoni

  DOI：10.1246/cl.2009.750

  日期：2009.7.5

  Boronic esters are key intermediates in the synthesis of biologically active compounds such as thrombin and proteasome inhibitors. However, they have low hydrolytic stability both during synthetic reactions and in biological media. We report the preparation of several boronic esters and a comparative study of their stability to hydrolysis vs. the corresponding pinanediol boronic esters, which are among the most hydrolytically stable. We discovered that the boronic esters derived from (1,1′-bicyclohexyl)-1,1′-diol are the most stable among those examined.

  硼酸酯是合成生物活性化合物（如凝血酶和蛋白酶体抑制剂）的关键中间体。然而，它们在合成反应过程中以及在生物介质中均表现出较低的水解稳定性。我们报道了多种硼酸酯的制备及其与相应的水解稳定性较高的二氢二醇硼酸酯的稳定性对比研究。我们发现，由(1,1′-双环己基)-1,1′-二醇衍生的硼酸酯在所研究的样品中水解稳定性最高。
• Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)
  作者：Kenneth D. Rice、Naing Aay、Neel K. Anand、Charles M. Blazey、Owen J. Bowles、Joerg Bussenius、Simona Costanzo、Jeffry K. Curtis、Steven C. Defina、Larisa Dubenko、Stefan Engst、Anagha A. Joshi、Abigail R. Kennedy、Angie I. Kim、Elena S. Koltun、Julie C. Lougheed、Jean-Claire L. Manalo、Jean-Francois Martini、John M. Nuss、Csaba J. Peto、Tsze H. Tsang、Peiwen Yu、Stuart Johnston

  DOI：10.1021/ml300049d

  日期：2012.5.10

  The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and is constitutively activated or highly upregulated in many tumor types. Mutations associated with upstream pathway components RAS and Raf occur frequently and contribute to the oncogenic phenotype through activation of MEK and then ERK. Inhibitors of MEK have been shown to effectively block upregulated ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated early evidence of efficacy in the clinic for the treatment of cancer. Guided by structural insight, a strategy aimed at the identification of an optimal diphenylamine-based MEK inhibitor with an improved metabolism and safety profile versus PD-0325901 led to the discovery of development candidate 1-(3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo in preclinical models with sustained duration of action and is currently in early stage clinical trials. potency and efficacy in preclinical models with sustained duration of action and is currently in early stage clinical trials.