3-[4-(methoxycarbonylamino)phenoxy]-1,2-epoxypropane | 50714-59-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[4-(methoxycarbonylamino)phenoxy]-1,2-epoxypropane
• 英文别名: methyl [4-(oxiran-2-yl methoxy)phenyl]carbamate；methyl N-[4-(2,3-epoxypropoxy)phenyl]carbamate；Methyl {4-[(oxiran-2-yl)methoxy]phenyl}carbamate；methyl N-[4-(oxiran-2-ylmethoxy)phenyl]carbamate
• CAS: 50714-59-5
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: LTRJGONAQJAAGC-UHFFFAOYSA-N

物化性质

• 熔点：
  98 °C(Solv: chloroform (67-66-3); ligroine (8032-32-4)(2:1))
• 沸点：
  313.8±17.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  60.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[4-(methoxycarbonylamino)phenoxy]-1,2-epoxypropane 、 苄胺 以 1,4-二氧六环 为溶剂， 反应 6.0h， 以82%的产率得到methyl N-[4-(3-benzylamino-2-hydroxypropoxy)phenyl]carbamate
  参考文献：
  名称：

  Synthesis of Methyl-N-[4-(3-R-amino-2-hydroxypropoxy)phenyl]carbamates

  摘要：

  By alkylation of methyl-N-(4-hydroxyphenyl) carbamate with (chloroniethyl)oxirane in acetone in the presence of K2CO3 methyl-N-[4-(2,3-epoxypropoxy)phenyl]carbamate was prepared. The aminolysis of the latter effected by benzylamine, morpholine, piperidine, and pyrrolidine occurs in keeping with Krasusky rule to afford methyl-N-[4-(3-R-amino-2-hydroxypropoxy)phenyl]carbamates.

  DOI：

  10.1023/b:rujo.0000034939.01295.42
• 作为产物：
  描述：

  对氨基苯酚 在 吡啶 、 potassium hydroxide 作用下， 以 乙醚 为溶剂， 生成 3-[4-(methoxycarbonylamino)phenoxy]-1,2-epoxypropane
  参考文献：
  名称：

  An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors

  摘要：

  Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b] pyrimido[5,4-f]azepine and two alkyl{3-/4-[-1-hydroxy-2-(4-arylpiperazin-1-yl)ethyliphenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.08.017

文献信息

• Synthesis of Potentially β-Blocking Practolol Derivatives: (E +Z)-3-[4-(3-Iodoprop-2-enyloxycarbonylamino)phenoxy]-1-(isopropylamino)propan-2-ol
  作者：Marcel Apparu、Younes Ben Tiba、Pierre-Marc Léo、Daniel Fagret

  DOI：10.1002/(sici)1099-0690(200003)2000:6<1007::aid-ejoc1007>3.0.co;2-i

  日期：2000.3

  route chosen, from 4-aminophenol and the chloroformate β7, had to be abandoned because of the formation of the oxazolidinone 10 during the epoxidation step. The aminoalcohol 17 prepared from the practolol 1 finally gave the target compounds by condensation with the iodoallylic chloroformates 8 (E + Z). The secondary Boc-protected amine function was regenerated without removing the carbamate function

  合成了具有潜在 β 阻断特性的碘化氨基甲酸酯 3 (E + Z)。由于在环氧化步骤中形成恶唑烷酮 10，必须放弃从 4-氨基苯酚和氯甲酸酯 β7 中选择的第一条路线。由普拉考洛尔 1 制备的氨基醇 17 最终通过与碘代烯丙基氯甲酸酯 8 (E + Z) 缩合得到目标化合物。通过使用温和的反应条件 (1 N HCl)，在不去除位于 p 位的氨基甲酸酯官能团的情况下再生了仲 Boc 保护的胺官能团。
• Synthesis and structure-activity relationships of new β-adrenoreceptor antagonists. Evidence for the electrostatic requirements for β-adrenoreceptor antagonists
  作者：V Kettmann、J Csöllei、E Račanská、P Švec

  DOI：10.1016/0223-5234(91)90127-9

  日期：1991.12

  A series of mono- and disubstituted phenoxypropanolamines, structurally related to practolol and acebutolol, has been synthesized and tested for beta-adrenoreceptor blocking activity. Structure-activity relationships are discussed. The reasons for the lack of activity of compounds 3n and 4n have also been examined. The results suggest that the negative electrostatic potential above the phenyl ring of phenoxypropanolamines is essential for binding activity and point to the presence of an electropositive residue in the beta-adrenoreceptor binding site.
• .beta.-Adrenoceptor blocking agents. 1. Cardioselective 1-aryloxy-3-(aryloxyalkylamino)propan-2-ols
  作者：J. Augstein、D. A. Cox、A. L. Ham、P. R. Leeming、M. Sanrey

  DOI：10.1021/jm00269a007

  日期：1973.11
• CSOLLEI, J.;BOROVANSKY, A.;BENES, L.;BEDEROVA, E.;SVEC, P., CS. FARM., 1982, 31, N 6, 229-235
  作者：CSOLLEI, J.、BOROVANSKY, A.、BENES, L.、BEDEROVA, E.、SVEC, P.

  DOI：——

  日期：——
• An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors
  作者：Marcela Vettorazzi、Emilio Angelina、Santiago Lima、Tomas Gonec、Jan Otevrel、Pavlina Marvanova、Tereza Padrtova、Petr Mokry、Pavel Bobal、Lina M. Acosta、Alirio Palma、Justo Cobo、Janette Bobalova、Jozef Csollei、Ivan Malik、Sergio Alvarez、Sarah Spiegel、Josef Jampilek、Ricardo D. Enriz

  DOI：10.1016/j.ejmech.2017.08.017

  日期：2017.10

  Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b] pyrimido[5,4-f]azepine and two alkyl3-/4-[-1-hydroxy-2-(4-arylpiperazin-1-yl)ethyliphenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands. (C) 2017 Elsevier Masson SAS. All rights reserved.