乙基(1S,3S,5S)-2-氮杂双环[3.1.0]己烷-3-羧酸酯 | 361440-57-5

• 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
• 中文名称: 乙基(1S,3S,5S)-2-氮杂双环[3.1.0]己烷-3-羧酸酯
• 中文别名: (1S,3S,5S)-2-氮杂双环[3.1.0]己烷-3-甲酸
• 英文名称: ethyl (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxylate
• CAS: 361440-57-5
• 化学式: C₈H₁₃NO₂
• 分子量: 155.197
• InChiKey: IYUHWHWDNFNLTR-ACZMJKKPSA-N

物化性质

• 沸点：
  212.6±23.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙基(1S,3S,5S)-2-氮杂双环[3.1.0]己烷-3-羧酸酯 在 盐酸 、 lithium aluminium tetrahydride 、 palladium 10% on activated carbon 、 水 、 氢气 、 戴斯-马丁氧化剂 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸酐 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

  摘要：

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.055
• 作为产物：
  描述：

  (S)-1-N-叔丁氧羰基-2,3-二氢-2-吡咯甲酸乙酯 在 diethylzinc 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 乙基(1S,3S,5S)-2-氮杂双环[3.1.0]己烷-3-羧酸酯
  参考文献：
  名称：

  4,5-顺式和反-Methano-L-脯氨酸低聚物的结构性质和立体化学上独特的折叠偏好：最短的结晶PPII型螺旋脯氨酸螺旋四聚物

  摘要：

  X射线晶体学，圆二色性测量表明，以顺式和反式-4,5-甲基-L-脯氨酸酰胺为代表的一系列L-脯氨酸甲醇类似物的合成，结构性质和折叠模式和DFT计算。我们公开了显示聚脯氨酸II螺旋构象的结晶四聚脯氨酸同类物的第一个实例。反映反酰胺的n→π*稳定程度的理论计算结果证明了顺式-4,5-甲基-L-脯氨酸低聚物的PPII型螺旋排列（溶液形式和固态形式）的实验证据构象。

  DOI：

  10.1002/anie.201506208

文献信息

• [EN] CYCLIN-DEPENDENT KINASE 7 (CDK7) NON-COVALENT INHIBITORS<br/>[FR] INHIBITEURS NON COVALENTS DE KINASE CYCLINE-DÉPENDANTE 7 (CDK7)
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2022064009A1

  公开（公告）日：2022-03-31

  The invention relates to pharmaceutical compounds of formula (I) and pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds as inhibitors of cyclin-dependent kinase 7 (CDK7) and to their use in the treatment of diseases, e.g. cancer.

  这项发明涉及公式（I）的药物化合物和包含这些化合物的药物组合物，以及用于制备这些化合物的过程，以及将这些化合物用作细胞周期依赖性激酶7（CDK7）的抑制剂，并将其用于治疗疾病，例如癌症。
• Properties of the Amide Bond Involving Proline 4,5-methanologues: an Experimental and Theoretical Study
  作者：Gilles Berger、Ingrid Chab-Majdalani、Stephen Hanessian

  DOI：10.1002/ijch.201600106

  日期：2017.4

  Herein we disclose a combined experimental and theoretical study on the conformational properties of amide bonds involving diastereomeric 4,5‐methano‐L‐proline congeners as N‐acetyl ethyl esters and dimeric amide ethyl esters as substrates for cyclization to diketopiperazines. The results are discussed in light of density functional theory calculations aimed at delineating the importance of the n→π*

  本文中，我们公开了涉及非对映体4,5--甲基-L-脯氨酸同类物（作为N-乙酰乙基酯）和二聚酰胺乙酯（作为环化成二酮哌嗪的底物）的酰胺键构象特性的组合实验和理论研究。根据密度泛函理论计算讨论了结果，目的是描述反酰胺构象的n →π*稳定化的重要性。计算了非对映体4,5-甲醇-L-脯氨酸乙酯环化成二酮哌嗪的过渡态，并将其与实验研究相关联。
• Structural Properties and Stereochemically Distinct Folding Preferences of 4,5‐ <i>cis</i> and <i>trans</i> ‐Methano‐ <scp>L</scp> ‐Proline Oligomers: The Shortest Crystalline PPII‐Type Helical Proline‐Derived Tetramer
  作者：Gilles Berger、Miguel Vilchis‐Reyes、Stephen Hanessian

  DOI：10.1002/anie.201506208

  日期：2015.11.2

  synthesis, structural properties, and folding patterns of a series of L‐proline methanologues represented by cis‐ and trans‐4,5‐methano‐L‐proline amides and their oligomers are reported as revealed by X‐ray crystallography, circular dichroism measurements, and DFT calculations. We disclose the first example of a crystalline tetrameric proline congener to exhibit a polyproline II helical conformation

  X射线晶体学，圆二色性测量表明，以顺式和反式-4,5-甲基-L-脯氨酸酰胺为代表的一系列L-脯氨酸甲醇类似物的合成，结构性质和折叠模式和DFT计算。我们公开了显示聚脯氨酸II螺旋构象的结晶四聚脯氨酸同类物的第一个实例。反映反酰胺的n→π*稳定程度的理论计算结果证明了顺式-4,5-甲基-L-脯氨酸低聚物的PPII型螺旋排列（溶液形式和固态形式）的实验证据构象。
• Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction
  作者：Weidong Pan、Brian R. Lahue、Yao Ma、Latha G. Nair、Gerald W. Shipps、Yaolin Wang、Ronald Doll、Stéphane L. Bogen

  DOI：10.1016/j.bmcl.2014.02.055

  日期：2014.4

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.