N-(5-bromo-2-pyridinyl)-N'-[2-(2-methoxycarbonylmethyloxy-5-methoxyphenyl)ethyl]thiourea | 1101872-66-5

• 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: N-(5-bromo-2-pyridinyl)-N'-[2-(2-methoxycarbonylmethyloxy-5-methoxyphenyl)ethyl]thiourea
• 英文别名: Methyl 2-[2-[2-[(5-bromo-2-pyridyl)carbamothioylamino]ethyl]-4-methoxy-phenoxy]acetate；methyl 2-[2-[2-[(5-bromopyridin-2-yl)carbamothioylamino]ethyl]-4-methoxyphenoxy]acetate
• CAS: 1101872-66-5
• 化学式: C₁₈H₂₀BrN₃O₄S
• 分子量: 454.344
• InChiKey: VTOSZXLXXLIBGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(tert-butoxycarbonyl)-2-(2-methoxycarbonylmethyloxy-5-methoxyphenyl)ethylamine 、 imidazole-1-carbothionic acid (5-bromopyridin-2-yl)amide 在 三氟乙酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 22.17h， 以50%的产率得到N-(5-bromo-2-pyridinyl)-N'-[2-(2-methoxycarbonylmethyloxy-5-methoxyphenyl)ethyl]thiourea
  参考文献：
  名称：

  C-2-Aryl O-substituted HI-236 derivatives as non-nucleoside HIV-1 reverse-transcriptase inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.10.048

文献信息

• 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.