1,14-bis(imidazol-1-yl)tetradecane dihydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,14-bis(imidazol-1-yl)tetradecane dihydrochloride
• 英文别名: 1,14-bis-(1H-imidazol-1-yl)tetradecane dihydrochloride；1-(14-Imidazol-1-yltetradecyl)imidazole;hydrochloride
• 化学式: C₂₀H₃₄N₄*2ClH
• 分子量: 403.439
• InChiKey: UFYBILPQNOKVSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  25
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,14-十四烷二醇 在 磷酸 、 phosphorus pentoxide 、 potassium iodide 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 8.5h， 生成 1,14-bis(imidazol-1-yl)tetradecane dihydrochloride
  参考文献：
  名称：

  The anti-malarial activity of bivalent imidazolium salts

  摘要：

  A series of compounds containing bivalent imidazolium rings and one triazolium analog were synthesized and evaluated for their ability to inhibit the replication of Plasmodium falciparum cultures. The activity and selectivity of the compounds for P. falciparum cultures were found to depend on the presence of electron-deficient rings that were spaced an appropriate distance apart. The activity of the compounds was not critically dependent on the nature of the linker between the electron-deficient rings, an observation that suggests that the rings were responsible for the primary interaction with the molecular target of the compounds in the parasite. The bivalent imidazolium and triazolium compounds disrupted the process whereby merozoites gain entry into erythrocytes, however, they did not appear to prevent merozoites from forming. The compounds were also found to be active in a murine Plasmodium berghei infection, a result consistent with the compounds specifically interacting with a parasite component that is required for replication and is conserved between two Plasmodium species. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.002

文献信息

• Bis-imidazoles as molecular probes for peripheral sites of the zinc endopeptidase of botulinum neurotoxin serotype A
  作者：Isidro Merino、Jason D. Thompson、Charles B. Millard、James J. Schmidt、Yuan-Ping Pang

  DOI：10.1016/j.bmc.2006.01.015

  日期：2006.5

  Botulinum neurotoxin serotype A (BoNTA) is highly toxic, and its antidote is currently unavailable. The essential light-chain subunit of BoNTA is a zinc endopeptidase that can be used as a target for developing antidotes. However, the development of high-affinity, small-molecule inhibitors of the endopeptidase is as challenging as the development of small-molecule inhibitors of protein-protein complexation. This is because the polypeptide substrate wraps around the circumference of the endopeptidase upon binding, thereby constituting an unusually large substrate-enzyme interface of 4840 angstrom(2). To overcome the large-interface problem, we propose using the zinc-coordination and bivalence approaches to design inhibitors of BoNTA. Here we report the development of alkylene-linked bis-imidazoles that inhibit the endopeptidase in a two-site binding mode, The bis-imidazole tethered with 13 methylene groups, the most potent of the alkylene-linked dimers, showed 61% inhibition of the zinc endopeptidase of BoNTA at a concentration of 100 mu M. The results demonstrate the presence of a peripheral binding site for an imidazolium group at the rim of the BoNTA active-site cleft. This peripheral site enables the use of the bivalence approach to improve Our previously reported small-molecule inhibitors that were developed according to the zinc-coordination approach. (c) 2006 Elsevier Ltd All rights reserved.