cis/cis-3,4,5-trimethoxybenzoic acid 4-[(4-hydroxycyclohexyl)methylamino]cyclohexyl ester | 929548-64-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis/cis-3,4,5-trimethoxybenzoic acid 4-[(4-hydroxycyclohexyl)methylamino]cyclohexyl ester
• CAS: 929548-64-1
• 化学式: C₂₃H₃₅NO₆
• 分子量: 421.534
• InChiKey: GDZXPLCOXWMNMS-FNCFJJJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  30.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  77.46
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  cis/cis-3,4,5-trimethoxybenzoic acid 4-[(4-hydroxycyclohexyl)methylamino]cyclohexyl ester 、 (E)-3-(3,4,5-trimethoxyphenyl)acryloyl chloride 以 氯仿 为溶剂， 反应 3.0h， 以98%的产率得到cis/cis-3,4,5-trimethoxybenzoic acid 4-(methyl{4-[3-(3,4,5-trimethoxyphenyl)acryloyloxy]cyclohexyl}amino)cyclohexyl ester
  参考文献：
  名称：

  Isomeric N,N-Bis(cyclohexanol)amine Aryl Esters:  The Discovery of a New Class of Highly Potent P-Glycoprotein (Pgp)-dependent Multidrug Resistance (MDR) Inhibitors

  摘要：

  A new series of P-glycoprotein (Pgp)-dependent multidrug resistance (MDR) inhibitors having a N,N-bis(cyclohexanol)amine scaffold have been designed, following the frozen analog approach. With respect to the parent flexible molecules, the new compounds show improved potency and efficacy. Among them, compound 1d, on anthracycline-resistant erythroleukemia K562 cells, is able to completely reverse Pgp-dependent MDR at low nanomolar concentration.

  DOI：

  10.1021/jm0614432
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酰氯 在 titanium(IV) isopropylate 、 甲酸 、 sodium cyanoborohydride 作用下， 以 乙醇 、 氯仿 、 苯 为溶剂， 反应 38.0h， 生成 cis/cis-3,4,5-trimethoxybenzoic acid 4-[(4-hydroxycyclohexyl)methylamino]cyclohexyl ester
  参考文献：
  名称：

  Isomeric N,N-Bis(cyclohexanol)amine Aryl Esters:  The Discovery of a New Class of Highly Potent P-Glycoprotein (Pgp)-dependent Multidrug Resistance (MDR) Inhibitors

  摘要：

  A new series of P-glycoprotein (Pgp)-dependent multidrug resistance (MDR) inhibitors having a N,N-bis(cyclohexanol)amine scaffold have been designed, following the frozen analog approach. With respect to the parent flexible molecules, the new compounds show improved potency and efficacy. Among them, compound 1d, on anthracycline-resistant erythroleukemia K562 cells, is able to completely reverse Pgp-dependent MDR at low nanomolar concentration.

  DOI：

  10.1021/jm0614432

文献信息

• Arylamino Esters As P-Glycoprotein Modulators: SAR Studies to Establish Requirements for Potency and Selectivity
  作者：Elisabetta Teodori、Silvia Dei、Elisa Floriddia、Maria Grazia Perrone、Dina Manetti、Maria Novella Romanelli、Marialessandra Contino、Nicola Antonio Colabufo

  DOI：10.1002/cmdc.201500143

  日期：2015.8

  basic aryl‐group‐containing compounds was synthesized with the aim of developing potent and selective P‐glycoprotein (P‐gp) modulators that are able to reverse multidrug resistance (MDR). The natures of the spacer (dicyclohexylamine or dialkylamine) and the aryl moieties were modified to investigate selectivity and the mechanism of P‐gp interaction. The inhibitory activities of the compounds toward P‐gp

  合成了一组碱性的含芳基化合物，目的是开发能够逆转多药耐药性（MDR）的有效和选择性P-糖蛋白（P-gp）调节剂。修饰了间隔基（二环己胺或二烷基胺）和芳基部分的性质，以研究选择性和P-gp相互作用的机理。评估了化合物对P‐gp，多药耐药相关蛋白1（MRP1）和乳腺癌耐药蛋白（BCRP）（与MDR最相关的ATP结合盒（ABC）转运蛋白）的抑制活性。通过三种生物学方法研究了每种化合物的P-gp相互作用机理：表观渗透率（P app）测定Caco-2细胞单层中的（B→A / A→B），ATP细胞耗竭并抑制MDCK-MDR1细胞中的Calcein-AM转运。这些测定使我们能够估计化合物对三个外排泵的选择性，并确定定义P-gp-相互作用曲线的结构要求。发现所有二环己胺衍生物都是P-gp底物，而一种二烷基胺衍生物被证明是P-gp抑制剂。一个顺式/顺式异构体的良好MRP1活性突出表明了它是开发MRP1配体的主要候选对象。