trans/trans 3,4,5-trimethoxybenzoic acid 4-(methyl-{4-[3-(3,4,5-trimethoxyphenyl)-propioloyloxy]cyclohexyl}amino)cyclohexyl ester

• 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: trans/trans 3,4,5-trimethoxybenzoic acid 4-(methyl-{4-[3-(3,4,5-trimethoxyphenyl)-propioloyloxy]cyclohexyl}amino)cyclohexyl ester
• 英文别名: [4-[Methyl-[4-[3-(3,4,5-trimethoxyphenyl)prop-2-ynoyloxy]cyclohexyl]amino]cyclohexyl] 3,4,5-trimethoxybenzoate
• 化学式: C₃₅H₄₅NO₁₀
• 分子量: 639.743
• InChiKey: TUDPGFIDCKVNGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  46
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  3-(3,4,5-trimethoxyphenyl)propiolic acid 、 cis/trans-3,4,5-trimethoxybenzoic acid 4-[(4-hydroxycyclohexyl)-methylamino]cyclohexyl ester 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以15%的产率得到trans/trans 3,4,5-trimethoxybenzoic acid 4-(methyl-{4-[3-(3,4,5-trimethoxyphenyl)-propioloyloxy]cyclohexyl}amino)cyclohexyl ester
  参考文献：
  名称：

  Inhibition of P-glycoprotein-mediated Multidrug Resistance (MDR) by N,N-bis(cyclohexanol)amine aryl esters: Further restriction of molecular flexibility maintains high potency and efficacy

  摘要：

  Conformational modulation of the aryl portion of a set of N,N-bis(cyclohexanol)amine aryl esters (1a-d) that are potent Pgp-dependent MDR inhibitors has been performed. Toward this end the trans-3-(3,4,5-trimethoxyphenyl) acrylic acid present in set 1 was substituted with 3-(3,4,5-trimethoxyphenyl) propanoic and 3-(3,4,5-trimethoxyphenyl) propiolic moieties to give sets 2 and 3, respectively. While the introduction of 3-(3,4,5-trimethoxyphenyl) propanoic moiety resulted in a definite drop in potency and efficacy, esterification with 3-(3,4,5-trimethoxyphenyl) propiolic acid gave four isomers (3a-d) that maintain high potency and possess optimal efficacy. These results are discussed in terms of conformational flexibility of the different sets of compounds. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.059

文献信息

• Inhibition of P-glycoprotein-mediated Multidrug Resistance (MDR) by N,N-bis(cyclohexanol)amine aryl esters: Further restriction of molecular flexibility maintains high potency and efficacy
  作者：Cecilia Martelli、Silvia Dei、Catherine Lambert、Dina Manetti、Francesca Orlandi、Maria Novella Romanelli、Serena Scapecchi、Milena Salerno、Elisabetta Teodori

  DOI：10.1016/j.bmcl.2010.11.059

  日期：2011.1

  Conformational modulation of the aryl portion of a set of N,N-bis(cyclohexanol)amine aryl esters (1a-d) that are potent Pgp-dependent MDR inhibitors has been performed. Toward this end the trans-3-(3,4,5-trimethoxyphenyl) acrylic acid present in set 1 was substituted with 3-(3,4,5-trimethoxyphenyl) propanoic and 3-(3,4,5-trimethoxyphenyl) propiolic moieties to give sets 2 and 3, respectively. While the introduction of 3-(3,4,5-trimethoxyphenyl) propanoic moiety resulted in a definite drop in potency and efficacy, esterification with 3-(3,4,5-trimethoxyphenyl) propiolic acid gave four isomers (3a-d) that maintain high potency and possess optimal efficacy. These results are discussed in terms of conformational flexibility of the different sets of compounds. (C) 2010 Elsevier Ltd. All rights reserved.