N,N’-bis[(1-adamantyl)methyl]-4,13-diaza-18-crown-6 | 1315247-76-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,N’-bis[(1-adamantyl)methyl]-4,13-diaza-18-crown-6
• 英文别名: N,N'-bis[(1-adamantylmethyl)]-1,10-diaza-18-crown-6；7,16-Bis(1-adamantylmethyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane
• CAS: 1315247-76-7
• 化学式: C₃₄H₅₈N₂O₄
• 分子量: 558.846
• InChiKey: XGIPHOMSJSEYRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  40
• 可旋转键数：
  4
• 环数：
  9.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N,N’-bis[1-oxo-1-(1-adamantyl)methyl]-4,13-diaza-18-crown-6 在 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 生成 N,N’-bis[(1-adamantyl)methyl]-4,13-diaza-18-crown-6
  参考文献：
  名称：

  氮杂冠醚的合成，生物评价和分子建模

  摘要：

  已经开发出合成的和天然的离子载体来催化离子迁移，并且已经显示出其具有多种生物学效应。我们合成了24个含金刚烷基，金刚烷基，氨基甲基苯甲酰基和ε-氨基己酰基取代基的氮杂和二氮杂冠醚，并在体外分析了它们的生物学效应。化合物的十（8，10 - 17，和21）增加的胞内钙（[钙2+ ]我在人嗜中性白细胞），其中最有效的感化合物15（Ñ，Ñ “ -双[2-（1-金刚烷基）乙酰基] -4,10-diaza-15-crown-5），表明这些化合物可以改变正常的中性粒细胞[Ca 2+ ] i通量。事实上，许多这些化合物的（即，8，10 - 17，和21）抑制的[Ca 2+ ]我磁通在由活化人中性粒细胞Ñ甲酰基肽（˚F MLF）。这些化合物中的一些还抑制趋化肽诱导的[Ca 2+ ] iN-甲酰基肽受体1或2（FPR1或FPR2）转染的HL60细胞中的“通量”。此外，几种活性化合物抑制佛波醇12-肉豆蔻酸酯1

  DOI：

  10.3390/molecules26082225

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.
• 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)
• Synthesis, Biological Evaluation, and Molecular Modeling of Aza-Crown Ethers
  作者：Stepan S. Basok、Igor A. Schepetkin、Andrei I. Khlebnikov、Anatoliy F. Lutsyuk、Tatiana I. Kirichenko、Liliya N. Kirpotina、Victor I. Pavlovsky、Klim A. Leonov、Darya A. Vishenkova、Mark T. Quinn

  DOI：10.3390/molecules26082225

  日期：——

  calculations were performed on five structure-related diaza-crown ethers and their complexes with Ca2+, Na+, and K+ to obtain a set of molecular electronic properties and to correlate these properties with biological activity. According to density-functional theory (DFT) modeling, Ca2+ ions were more effectively bound by these compounds versus Na+ and K+. The DFT-optimized structures of the ligand-Ca2+ complexes

  已经开发出合成的和天然的离子载体来催化离子迁移，并且已经显示出其具有多种生物学效应。我们合成了24个含金刚烷基，金刚烷基，氨基甲基苯甲酰基和ε-氨基己酰基取代基的氮杂和二氮杂冠醚，并在体外分析了它们的生物学效应。化合物的十（8，10 - 17，和21）增加的胞内钙（[钙2+ ]我在人嗜中性白细胞），其中最有效的感化合物15（Ñ，Ñ “ -双[2-（1-金刚烷基）乙酰基] -4,10-diaza-15-crown-5），表明这些化合物可以改变正常的中性粒细胞[Ca 2+ ] i通量。事实上，许多这些化合物的（即，8，10 - 17，和21）抑制的[Ca 2+ ]我磁通在由活化人中性粒细胞Ñ甲酰基肽（˚F MLF）。这些化合物中的一些还抑制趋化肽诱导的[Ca 2+ ] iN-甲酰基肽受体1或2（FPR1或FPR2）转染的HL60细胞中的“通量”。此外，几种活性化合物抑制佛波醇12-肉豆蔻酸酯1