methyl 3-(1-(3-(3-(tert-butoxycarbonyl amino)propoxy)-4-carbamothioylphenyl)-1H-imidazol-2-yl) propanoate | 1093098-95-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 3-(1-(3-(3-(tert-butoxycarbonyl amino)propoxy)-4-carbamothioylphenyl)-1H-imidazol-2-yl) propanoate
• 英文别名: methyl 3-(1-(3-(3-(tert-butoxycarbonylamino)propoxy)-4-carbamothioylphenyl)-1H-imidazol-2-yl)propanoate
• CAS: 1093098-95-3
• 化学式: C₂₂H₃₀N₄O₅S
• 分子量: 462.57
• InChiKey: LKFHFSVHTUFCFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  117.7
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl 3-(1-(3-(3-(tert-butoxycarbonyl amino)propoxy)-4-carbamothioylphenyl)-1H-imidazol-2-yl) propanoate 在 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 methyl 3-(1-(3-(3-aminopropoxy)-4-(4-ethoxythiazol-2-yl) phenyl)-1H-imidazol-2-yl) propanoate
  参考文献：
  名称：

  Expedient route to functionalized and water soluble 5-6-5 imidazole-phenyl-thiazole based α-helix mimetics

  摘要：

  A range of small molecule scaffolds have been shown to act as structural and functional mimics of alpha-helices by mimicking the i, i+4, and i+7 positions, often found at the interface of PPIs. These molecules, though potent, possess complicating features-either low water solubility, or maintenance of conformation by hydrogen-bonding networks. We have addressed these limitations by developing a scaffold with increased water solubility. Herein we present a rapid synthetic pathway to a library of 56 compounds based on a 5-6-5 scaffold, containing an imidazole-phenyl-thiazole core; the route is flexible and allows rapid installation of different substituents via high-yielding Ullman and Suzuki couplings and Hantsch thiazole syntheses. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.11.070
• 作为产物：
  描述：

  methyl 3-(1H-imidazol-2-yl)propanoate hydrochloride 在 copper(l) iodide 、 ammonium sulfide 、 potassium carbonate 、 L-脯氨酸 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 50.0h， 生成 methyl 3-(1-(3-(3-(tert-butoxycarbonyl amino)propoxy)-4-carbamothioylphenyl)-1H-imidazol-2-yl) propanoate
  参考文献：
  名称：

  Expedient route to functionalized and water soluble 5-6-5 imidazole-phenyl-thiazole based α-helix mimetics

  摘要：

  A range of small molecule scaffolds have been shown to act as structural and functional mimics of alpha-helices by mimicking the i, i+4, and i+7 positions, often found at the interface of PPIs. These molecules, though potent, possess complicating features-either low water solubility, or maintenance of conformation by hydrogen-bonding networks. We have addressed these limitations by developing a scaffold with increased water solubility. Herein we present a rapid synthetic pathway to a library of 56 compounds based on a 5-6-5 scaffold, containing an imidazole-phenyl-thiazole core; the route is flexible and allows rapid installation of different substituents via high-yielding Ullman and Suzuki couplings and Hantsch thiazole syntheses. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2012.11.070

文献信息

• Synthesis and Biological Evaluation of a 5-6-5 Imidazole-Phenyl-Thiazole Based α-Helix Mimetic
  作者：Christopher G. Cummings、Nathan T. Ross、William P. Katt、Andrew D. Hamilton

  DOI：10.1021/ol8022962

  日期：2009.1.1

  that disrupt protein−protein interactions is a key goal in addressing a number of disease states. The α-helix is commonly found at protein interaction interfaces and has been the focus of substantial small molecule mimetic efforts. One of the primary drawbacks of many small molecule α-helix mimetics is their hydrophobic core structures. To address this problem we have developed a novel scaffold based

  开发破坏蛋白质-蛋白质相互作用的小分子是解决许多疾病状态的关键目标。α-螺旋常见于蛋白质相互作用界面，并且一直是大量小分子模拟工作的重点。许多小分子 α-螺旋模拟物的主要缺点之一是它们的疏水核心结构。为了解决这个问题，我们开发了一种基于水溶性更好的 5-6-5 咪唑-苯基-噻唑核的新型支架。此类抑制剂已被证明可以在微摩尔浓度下破坏 Cdc42/Dbs 蛋白-蛋白相互作用，并且可能有助于克服 Cdc42 诱导的肿瘤对抗癌疗法的耐药性。