2-(3-硝基-苄基氨基)-乙醇 | 40172-07-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(3-硝基-苄基氨基)-乙醇
• 英文名称: 2-((3-nitrobenzyl)amino)ethanol
• 英文别名: 2-(3-nitrobenzylamino)ethanol；2-(3-nitro-benzylamino)-ethanol；2-(3-Nitro-benzylamino)-aethanol；2-[(3-nitrophenyl)methylamino]ethanol
• CAS: 40172-07-4
• 化学式: C₉H₁₂N₂O₃
• mdl: MFCD07407469
• 分子量: 196.206
• InChiKey: OGOJCOWNOXOGRY-UHFFFAOYSA-N

物化性质

• 熔点：
  76 °C(Solv: benzene (71-43-2))
• 沸点：
  378.8±22.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-硝基-苄基氨基)-乙醇 在 甲醇 、 tin(II) chloride dihdyrate 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[allyl-(3-aminobenzyl)amino]ethanol
  参考文献：
  名称：

  Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the Treatment of Cancer

  摘要：

  Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

  DOI：

  10.1021/jm201112g
• 作为产物：
  描述：

  间硝基苯甲醛 、 C.I.酸性橙108 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到2-(3-硝基-苄基氨基)-乙醇
  参考文献：
  名称：

  Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the Treatment of Cancer

  摘要：

  Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

  DOI：

  10.1021/jm201112g

文献信息

• New Uses for the Burgess Reagent in Chemical Synthesis: Methods for the Facile and Stereoselective Formation of Sulfamidates, Glycosylamines, and Sulfamides
  作者：K. C. Nicolaou、Scott A. Snyder、Deborah A. Longbottom、Annie Z. Nalbandian、Xianhai Huang

  DOI：10.1002/chem.200400503

  日期：2004.11.19

  Although the Burgess reagent (methoxycarbonylsulfamoyltriethylammonium hydroxide, inner salt) has found significant use in chemical synthesis as a dehydrating agent, almost no work has been directed towards its potential in other synthetic applications. As this article will detail, we have found that the Burgess reagent is remarkably effective at accomplishing a number of non-dehydrative synthetic

  尽管Burgess试剂（甲氧基羰基氨磺酰基三乙铵氢氧化物，内盐）已发现在化学合成中作为脱水剂具有重要用途，但几乎没有工作针对其在其他合成应用中的潜力。正如本文将要详细介绍的那样，我们发现，将Burgess试剂应用于适当的底物上，例如从1,2-二醇或环氧醇，α-和C-形成氨基磺酸盐时，在完成许多非脱水合成任务方面非常有效。来自碳水化合物的β-糖胺和来自1,2-氨基醇的环状磺酰胺 除了描述这些新反应歧管的功能之外，我们还描述了一组替代的Burgess型试剂的构造，这些试剂进一步扩展了这些新反应的范围。
• Ring Expansion of 3-Oxetanone-Derived Spirocycles: Facile Synthesis of Saturated Nitrogen Heterocycles
  作者：Stefan A. Ruider、Steffen Müller、Erick M. Carreira

  DOI：10.1002/anie.201306563

  日期：2013.11.4

  all: 4,5‐Spirocycles derived from 3‐oxetanone and β‐heteroatom‐substituted amino compounds undergo a Lewis acid mediated reaction cascade to form saturated nitrogen heterocycles. The unique reactivity of 3‐oxetanone facilitates access to biologically important morpholines, piperazines, and thiomorpholines with an otherwise difficult‐to‐access substitution pattern from readily available starting materials

  一环将它们全部带走：衍生自3-氧杂环丁酮和β-杂原子取代的氨基化合物的4,5-螺环经历路易斯酸介导的反应级联反应，形成饱和氮杂环。3-氧杂环丁酮具有独特的反应性，可方便地从重要的吗啉，哌嗪和硫代吗啉中获得，否则很难从容易获得的起始原料中获得取代模式。
• Synthesis of non-symmetrical sulfamides using burgess-type reagents
  申请人：The Scripps Research Institute

  公开号：US20040138448A1

  公开（公告）日：2004-07-15

  A practical and high-yielding method for the efficient, one-step synthesis of diverse classes of N,N′-differentiated sulfamides employs a wide range of amino alcohols and simple amines using Burgess-type reagents. This methodology extends the application and availability of sulfamides within the fields of chemical biology, medicinal chemistry, asymmetric synthesis, and supramolecular chemistry.

  一种实用且高产的方法，用于高效、一步合成多种类别的N,N′-差异化磺酰胺，利用广泛的氨基醇和简单胺类，使用伯吉斯型试剂。这种方法扩展了磺酰胺在化学生物学、药物化学、不对称合成和超分子化学领域的应用和可用性。
• Structural Studies on Bioactive Compounds. 34. Design, Synthesis, and Biological Evaluation of Triazenyl-Substituted Pyrimethamine Inhibitors of <i>Pneumocystis carinii</i> Dihydrofolate Reductase
  作者：David C. M. Chan、Charles A. Laughton、Sherry F. Queener、Malcolm F. G. Stevens

  DOI：10.1021/jm0108698

  日期：2001.8.1

  The triazenyl-pyrimethamine derivative 3a (TAB), a potent and selective inhibitor of Pneumocystis carinii DHFR, was selected as the starting point for a lead optimization study. Molecular modeling studies, corroborated by a recent crystal structure determination of the ternary complex of P. carinii DHFR--NADPH bound to TAB, predicted that modifications to the acetoxy residue of the lead inhibitor could

  选择了三氮烯基-乙胺嘧啶衍生物3a（TAB）（一种有效的选择性卡氏肺孢子虫DHFR抑制剂）作为前导优化研究的起点。分子建模研究得到了最近对TAB结合的Carinii DHFR-NADPH三元复合物晶体结构测定的证实，预测对铅抑制剂乙酰氧基残基的修饰可利用活性位点附近的结合机会由残基Ile33，Lys37和Leu72结合。预测用给电子基团和吸电子基团取代苄基部分可探测与卡氏疟原虫唯一的氨基酸Phe69的面缘相互作用。新的三氮烯10a-v和12a-f是通过将氨基乙胺的四氟硼酸重氮盐6b与取代的苄胺或苯乙胺偶联而制得的。在新的抗卡氏疟原虫DHFR抑制剂中，最有效的是萘基甲基取代的三氮烯10t（IC（50）：0.053 microM），但对大鼠肝脏DHFR的效价更大幅度的升高导致选择性降低（比率为大鼠肝脏DHFR IC（50）/卡氏毕赤酵母DHFR IC（50）：5.36）与原始铅结构3a的比率（大鼠肝脏DHFR
• 4-SUBSTITUENT-2-HYDROXYLMORPHOLINE-3-ONE AND PREPARATION METHOD THEREOF
  申请人：Zhejiang Hisun Pharmaceutical Co., Ltd.

  公开号：US20150087828A1

  公开（公告）日：2015-03-26

  A molecule with neural activities, especially 4-substituent-2-hydroxymorpholin-3-one, as a new intermediate of neurokinin-1 receptor antagonist aprepitant, and preparation method thereof.

  一种具有神经活性的分子，特别是4-取代-2-羟基吗啡啡咯啉-3-酮，作为神经激肽-1受体拮抗剂阿普利坦的新中间体，以及其制备方法。