3,9-bis(3-benzyloxybenzyl)-1,5,7,11-tetrakishydroxymethyl-6,12-diphenyl-3,9-diazahexacyclo[6.4.0.0(2.7).0(4.11).0(5.10)]dodecane | 1053418-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3,9-bis(3-benzyloxybenzyl)-1,5,7,11-tetrakishydroxymethyl-6,12-diphenyl-3,9-diazahexacyclo[6.4.0.0(2.7).0(4.11).0(5.10)]dodecane
• 英文别名: [5,7,11-Tris(hydroxymethyl)-6,12-diphenyl-3,9-bis[(3-phenylmethoxyphenyl)methyl]-3,9-diazapentacyclo[6.4.0.02,7.04,11.05,10]dodecan-1-yl]methanol
• CAS: 1053418-89-5
• 化学式: C₅₄H₅₄N₂O₆
• 分子量: 827.033
• InChiKey: ZJJHBNYDVBMXNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  62
• 可旋转键数：
  16
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tetraethyl 3,9-bis(3-benzyloxybenzyl)-6,12-diphenyl-3,9-diazahexacyclo[6.4.0.0(2.7).0(4.11).0(5.10)]dodecane-1,5,7,11-tetracarboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以69%的产率得到3,9-bis(3-benzyloxybenzyl)-1,5,7,11-tetrakishydroxymethyl-6,12-diphenyl-3,9-diazahexacyclo[6.4.0.0(2.7).0(4.11).0(5.10)]dodecane
  参考文献：
  名称：

  Novel Insight in Structure−Activity Relationship and Bioanalysis of P-Glycoprotein Targeting Highly Potent Tetrakishydroxymethyl Substituted 3,9-Diazatetraasteranes

  摘要：

  Novel 3,9-diazatetraasteranes have been synthesized with varied aromatic substitution patterns and evaluated as P-glycoprotein (P-gp) inhibitors. Structure-activity relationships (SAR) are discussed in relation to determined physicochemical properties. The potential to induce P-gp expression has been evaluated in cancer cell lines. The bioanalytical results indicate favorable noninducing properties compared to P-gp inducing drug standard.

  DOI：

  10.1021/jm800480y

文献信息

• Novel structure–activity relationships and selectivity profiling of cage dimeric 1,4-dihydropyridines as multidrug resistance (MDR) modulators
  作者：Claudius Coburger、Jörg Wollmann、Martin Krug、Christiane Baumert、Marianne Seifert、Joséf Molnár、Hermann Lage、Andreas Hilgeroth

  DOI：10.1016/j.bmc.2010.06.004

  日期：2010.7

  Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP) 1 and MRP2 inhibition are discussed and prove to be mainly determined by certain aromatic substitution patterns. The characterization of breast cancer resistance protein (BCRP) inhibition results in the discovery of benzyloxy substituted derivatives as selective P-gp inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.