N,N'-bis[1-oxo-3-(1-adamantyl)propyl]-1,10-diaza-18-crown-6 | 1258781-65-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N,N'-bis[1-oxo-3-(1-adamantyl)propyl]-1,10-diaza-18-crown-6
• 英文别名: N,N'-bis[1-oxo-3-(1-adamantyl)propyl]-4,13-diaza-18-crown-6；3-(1-Adamantyl)-1-[16-[3-(1-adamantyl)propanoyl]-1,4,10,13-tetraoxa-7,16-diazacyclooctadec-7-yl]propan-1-one
• CAS: 1258781-65-5
• 化学式: C₃₈H₆₂N₂O₆
• 分子量: 642.92
• InChiKey: ADRLSUSWDOZDLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  46
• 可旋转键数：
  6
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  77.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N,N'-bis[3-(1-adamantyl)propyl]-1,10-diaza-18-crown-6 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 N,N'-bis[1-oxo-3-(1-adamantyl)propyl]-1,10-diaza-18-crown-6
  参考文献：
  名称：

  Alkali Metal Ion Complexation of Adamantane Functionalized Diaza-bibracchial Lariat Ethers

  摘要：

  A series of adamantane functionalized diaza-lariat ethers 1-6 have been prepared and alkali metal picrate extraction profiles determined. The ability of aza-crown ethers 1-6 to extract the alkali metal picrates was compared with that of diaza-18-crown-6 (7) and N,N'-dibenzodiaza-18-crown-6 (8). Na+ and K+ transport across bulk liquid membrane was also measured. The results of alkali metal cation extraction experiments showed that lariat ethers 2 and 3, in which the adamantane molecule is linked to the diaza-18-crown-6 by amine bond, have better complexation abilities for all cations compared to the parent crown ethers 7 and 8, as well as a significantly higher selectivity for K+ than diaza-18-crown-6. However, diaza-lariat ether 1 showed reduced, and 4-6 negligible extractability towards any of the alkali cations. Monte Carlo conformational analysis pointed to the importance of conformational flexibility of the investigated compounds for their extraction ability of alkali cations.(doi: 10.5562/cca2100)

  DOI：

  10.5562/cca2100

文献信息

• Could LogP be a principal determinant of biological activity in 18-crown-6 ethers? Synthesis of biologically active adamantane-substituted diaza-crowns
  作者：Fran Supek、Tatjana Šumanovac Ramljak、Marko Marjanović、Maja Buljubašić、Goran Kragol、Nataša Ilić、Tomislav Šmuc、Davor Zahradka、Kata Mlinarić-Majerski、Marijeta Kralj

  DOI：10.1016/j.ejmech.2011.05.009

  日期：2011.8

  18-crown-6 ethers are known to exert their biological activity by transporting K+ ions across cell membranes. Using non-linear Support Vector Machines regression, we searched for structural features that influence antiproliferative activity in a diverse set of 19 known oxa-, monoaza- and diaza-18-crown-6 ethers. Here, we show that the logP of the molecule is the most important molecular descriptor, among similar to 1300 tested descriptors, in determining biological potency (R-cv(2), = 0.704). The optimal logP was at 5.5 (Ghose-Crippen ALOGP estimate) while both higher and lower values were detrimental to biological potency. After controlling for logP, we found that the antiproliferative activity of the molecule was generally not affected by side chain length, molecular symmetry, or presence of side chain amide links. To validate this QSAR model, we synthesized six novel, highly lipophilic diaza-18-crown-6 derivatives with adamantane moieties attached to the side arms. These compounds have near-optimal logP values and consequently exhibit strong growth inhibition in various human cancer cell lines and a bacterial system. The bioactivities of different diaza-18-crown-6 analogs in Bacillus subtilis and cancer cells were correlated, suggesting conserved molecular features may be mediating the cytotoxic response. We conclude that relying primarily on the logP is a sensible strategy in preparing future 18-crown-6 analogs with optimized biological activity. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Adamantane Derivatives Of Aza-Crown Ethers And Their Use In Treatment Of Tumor
  申请人：Kralj Marijeta

  公开号：US20110257254A1

  公开（公告）日：2011-10-20

  The invention relates to adamantane diaza-crown ether derivatives and the use of mono and diaza-crown ether adamantine derivatives in treatment, especially in tumor treatment. Adamantane aza-crown ethers were obtained by reaction of the corresponding adamantane derived tosylates or adamantane acid chlorides with mono- and diaza-18-crown-6. The prepared compounds showed moderate (monoaza-18-crown-6) to strong (diaza-18-crown-6) antiproliferative and cytotoxic activity on several tumor cell lines, revealing their potential for inhibiting the growth of other tumor cells.
• US8389505B2
  申请人：——

  公开号：US8389505B2

  公开（公告）日：2013-03-05
• Alkali Metal Ion Complexation of Adamantane Functionalized Diaza-bibracchial Lariat Ethers
  作者：Tatjana Šumanovac Ramljak、Kata Mlinarić-Majerski、Branimir Bertoša

  DOI：10.5562/cca2100

  日期：——

  A series of adamantane functionalized diaza-lariat ethers 1-6 have been prepared and alkali metal picrate extraction profiles determined. The ability of aza-crown ethers 1-6 to extract the alkali metal picrates was compared with that of diaza-18-crown-6 (7) and N,N'-dibenzodiaza-18-crown-6 (8). Na+ and K+ transport across bulk liquid membrane was also measured. The results of alkali metal cation extraction experiments showed that lariat ethers 2 and 3, in which the adamantane molecule is linked to the diaza-18-crown-6 by amine bond, have better complexation abilities for all cations compared to the parent crown ethers 7 and 8, as well as a significantly higher selectivity for K+ than diaza-18-crown-6. However, diaza-lariat ether 1 showed reduced, and 4-6 negligible extractability towards any of the alkali cations. Monte Carlo conformational analysis pointed to the importance of conformational flexibility of the investigated compounds for their extraction ability of alkali cations.(doi: 10.5562/cca2100)