1-Bromo-8-tert-butoxycarbonylamino-7-oxo-3-oxa-6-aza-1(1,4),4(1,4)-dibenzaoctaphane | 169267-65-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-Bromo-8-tert-butoxycarbonylamino-7-oxo-3-oxa-6-aza-1(1,4),4(1,4)-dibenzaoctaphane
• 英文别名: tert-butyl N-[[4-[(4-bromophenyl)methoxy]phenyl]methyl]carbamate
• CAS: 169267-65-6
• 化学式: C₁₉H₂₂BrNO₃
• 分子量: 392.293
• InChiKey: LCSYYYPUQHMQPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-Bromo-8-tert-butoxycarbonylamino-7-oxo-3-oxa-6-aza-1(1,4),4(1,4)-dibenzaoctaphane 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 11-Bromo-5-amino-3-oxa-1(1,4),4(1,4)-dibenzapentaphane
  参考文献：
  名称：

  Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction

  摘要：

  Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal "lid" segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111588
• 作为产物：
  描述：

  4-溴苄醇 在 dimethyl sulfide borane 、 邻苯二甲酸二异戊酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-Bromo-8-tert-butoxycarbonylamino-7-oxo-3-oxa-6-aza-1(1,4),4(1,4)-dibenzaoctaphane
  参考文献：
  名称：

  肽受体的修饰合成和结合特性

  摘要：

  大环受体9已经以同手性形式制备。该受体显示出对某些二肽的选择性，最值得注意的是，相对于N - Cbz-β-丙氨酰乳酸，N - Cbz-β-丙氨酰氨基酸的强烈偏好。

  DOI：

  10.1016/s0040-4039(97)00068-3

文献信息

• Synthesis and binding properties of a peptide receptor
  作者：Stephen S. Flack、Jeremy D. Kilburn

  DOI：10.1016/0040-4039(95)00494-w

  日期：1995.5

  Macrocyclic receptor 2, with an amidopyridine unit as the binding site for carboxylic acid functionality and amide functionality to provide additional hydrogen bonding sites, has been synthesised. Preliminary binding studies with 2 and various peptidic guests are described.

  已经合成了具有酰胺基吡啶单元作为羧酸官能团和酰胺官能团的结合位点以提供另外的氢键合位点的大环受体2。描述了与2和各种肽客体的初步结合研究。
• Modified synthesis and binding properties of a peptide receptor
  作者：James Dowden、Peter D. Edwards、Jeremy D. Kilburn

  DOI：10.1016/s0040-4039(97)00068-3

  日期：1997.2

  Macrocyclic receptor 9, has been prepared in homochiral form. The receptor shows selectivity for certain dipeptides, and most notably a strong preference for N-Cbz-β-alanyl amino acids over N-Cbz-β-alanyl lactic acids.

  大环受体9已经以同手性形式制备。该受体显示出对某些二肽的选择性，最值得注意的是，相对于N - Cbz-β-丙氨酰乳酸，N - Cbz-β-丙氨酰氨基酸的强烈偏好。
• Synthesis and Binding Properties of a Macrocyclic Peptide Receptor
  作者：James Dowden、Peter D. Edwards、Stephen S. Flack、Jeremy D. Kilburn

  DOI：10.1002/(sici)1521-3765(19990104)5:1<79::aid-chem79>3.0.co;2-w

  日期：1999.1.4
• Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction
  作者：Constantinos G. Neochoritis、Jack Atmaj、Aleksandra Twarda-Clapa、Ewa Surmiak、Lukasz Skalniak、Lisa-Maria Köhler、Damian Muszak、Katarzyna Kurpiewska、Justyna Kalinowska-Tłuścik、Barbara Beck、Tad A. Holak、Alexander Dömling

  DOI：10.1016/j.ejmech.2019.111588

  日期：2019.11

  Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal "lid" segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.