N-(tert-butoxycarbonyl)-2-(2-benzyloxy-5-methoxyphenyl)ethylamine | 939985-82-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(tert-butoxycarbonyl)-2-(2-benzyloxy-5-methoxyphenyl)ethylamine
• 英文别名: tert-butyl N-[2-(2-benzyloxy-5-methoxyphenyl)ethyl]-carbamate
• CAS: 939985-82-7
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: ZGQRXPOACXWVHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  56.79
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-2-(2-benzyloxy-5-methoxyphenyl)ethylamine 在 palladium on activated charcoal 、 四(三苯基膦)钯 copper(l) iodide 、 氢气 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 129.0h， 生成 5-{4-[(2-((5-bromo-2-pyridinyl)aminothiocarbonylamino)-ethyl)-4-methoxyphenoxy]but-1-ynyl}-5'-O-benzoyl-2',3'-didehydro-2',3'-dideoxyuridine
  参考文献：
  名称：

  [d4U]-butyne-[HI-236] as a non-cleavable, bifunctional NRTI/NNRTI HIV-1 reverse-transcriptase inhibitor

  摘要：

  The synthesis of bifunctional compound 10 consisting of d4U joined at C-5 to a butynyl spacer attached to HI-236 is reported using a Sonogashira coupling as a key step. As a non-cleavable bifunctional HIV inhibitor incorporating an NRTI with an NNRTI, 10 shows good inhibitory activity (EC50 = 250 nM) against HIV (IIIB) replication in NIT-2 cell culture, which is eight times greater than that of d4T and between those of the two component drugs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.107
• 作为产物：
  描述：

  2-苄氧基-5-甲氧基-苯甲醛 在 lithium aluminium tetrahydride 、 ammonium acetate 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 18.0h， 生成 N-(tert-butoxycarbonyl)-2-(2-benzyloxy-5-methoxyphenyl)ethylamine
  参考文献：
  名称：

  [d4U]-butyne-[HI-236] as a non-cleavable, bifunctional NRTI/NNRTI HIV-1 reverse-transcriptase inhibitor

  摘要：

  The synthesis of bifunctional compound 10 consisting of d4U joined at C-5 to a butynyl spacer attached to HI-236 is reported using a Sonogashira coupling as a key step. As a non-cleavable bifunctional HIV inhibitor incorporating an NRTI with an NNRTI, 10 shows good inhibitory activity (EC50 = 250 nM) against HIV (IIIB) replication in NIT-2 cell culture, which is eight times greater than that of d4T and between those of the two component drugs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.107

文献信息

• [d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase
  作者：Yassir Younis、Roger Hunter、Clare I. Muhanji、Ian Hale、Rajinder Singh、Christopher M. Bailey、Todd J. Sullivan、Karen S. Anderson

  DOI：10.1016/j.bmc.2010.05.025

  日期：2010.7

  propargyl-4-PEG (15d) have been synthesized and biologically evaluated as RT inhibitors against HIV-1. The key step in their synthesis involved a Sonogashira coupling of 5-iodo d4U’s benzoate with an alkynylated tethered HI-236 precursor followed by introduction of the HI-236 thiourea functionality. Biological evaluation in both cell-culture (MT-2 cells) as well as using an in vitro RT assay revealed 15a–c to

  [d4U]-间隔基-[HI-236] 类型的四种双药 HIV NRTI/NNRTI 抑制剂15a – d，其中间隔基变化为 1-丁炔基 ( 15a )、炔丙基-1-PEG ( 15b )、炔丙基-2-PEG ( 15c ) 和炔丙基-4-PEG ( 15d ) 已被合成并作为抗 HIV-1 的 RT 抑制剂进行生物学评估。他们合成的关键步骤涉及 5-碘 d4U 苯甲酸酯与炔基化 HI-236 前体的 Sonogashira 偶联，然后引入 HI-236 硫脲官能团。细胞培养（MT-2 细胞）以及使用体外 RT 测定的生物学评估显示15a – c比 d4T 更活跃。然而，总体而言，结果表明衍生物作为链延长的 NNRTIs，其中对于15b - d，核苷组分可能位于口袋外，但没有证据表明 NRTI 和 NNRTI 位点之间存在任何协同双结合。这部分归因于由于激酶识别失败导致双药核苷组分缺乏磷酸化，而结合
• C-2-Aryl O-substituted HI-236 derivatives as non-nucleoside HIV-1 reverse-transcriptase inhibitors
  作者：Roger Hunter、Yassir Younis、Clare I. Muhanji、Tanith-lea Curtin、Kevin J. Naidoo、Melissa Petersen、Christopher M. Bailey、Aravind Basavapathruni、Karen S. Anderson

  DOI：10.1016/j.bmc.2008.10.048

  日期：2008.12.15

  Several novel thiourea derivatives of the NNRTI HI-236 substituted at the C-2 oxygen of the phenyl ring have been synthesized and evaluated for their inhibitory activity against HIV-1 ( IIIB) replication in MT-2 cell cultures. The compounds were synthesized in order to fine-tune the activity of HI-236 as well as to gain insight into spatial characteristics in the pocket pertaining to the positional choice of tether in the design of [NRTI]-tether-[HI-236] bifunctional inhibitors. Two of the thiourea derivatives bearing a butynyl (6c) or hydroxyethyl tether (6n) were endowed with improved anti-HIV activity compared to HI-236. NNRTI activity was confirmed by a cell-free RT assay on six of the derivatives in which 6c returned an IC50 of 3.8 nM compared to 28 nM for HI-236, establishing it as an improved lead for HI-236. The structure-activity pro. le is discussed in terms of potential interactions in the NNRTI pocket as suggested by a docking model using AutoDock, which have a bearing on the bifunctional drug design. (C) 2008 Elsevier Ltd. All rights reserved.