[2-(2-hydroxy-3-piperazine-1-ylpropoxy)phenyl]phenylmethanone | 1370320-72-1

• 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: [2-(2-hydroxy-3-piperazine-1-ylpropoxy)phenyl]phenylmethanone
• 英文别名: [2-(2-Hydroxy-3-piperazin-1-ylpropoxy)phenyl]-phenylmethanone
• CAS: 1370320-72-1
• 化学式: C₂₀H₂₄N₂O₃
• 分子量: 340.422
• InChiKey: HZPIVWFAMCGVGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-(2-hydroxy-3-piperazine-1-ylpropoxy)phenyl]phenylmethanone 、 对甲苯异氰酸酯 以 二氯甲烷 为溶剂， 反应 2.0h， 以52.56%的产率得到4-[3-(2-benzoylphenoxy)-2-hydroxypropyl]piperazine-1-carboxylic acid p-tolylamide
  参考文献：
  名称：

  Structure–Activity Relationships, Ligand Efficiency, and Lipophilic Efficiency Profiles of Benzophenone-Type Inhibitors of the Multidrug Transporter P-Glycoprotein

  摘要：

  The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.

  DOI：

  10.1021/jm201705f
• 作为产物：
  描述：

  2-羟基二苯甲酮 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 [2-(2-hydroxy-3-piperazine-1-ylpropoxy)phenyl]phenylmethanone
  参考文献：
  名称：

  Structure–Activity Relationships, Ligand Efficiency, and Lipophilic Efficiency Profiles of Benzophenone-Type Inhibitors of the Multidrug Transporter P-Glycoprotein

  摘要：

  The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.

  DOI：

  10.1021/jm201705f

文献信息

• Structure–Activity Relationships, Ligand Efficiency, and Lipophilic Efficiency Profiles of Benzophenone-Type Inhibitors of the Multidrug Transporter P-Glycoprotein
  作者：Ishrat Jabeen、Karin Pleban、Uwe Rinner、Peter Chiba、Gerhard F. Ecker

  DOI：10.1021/jm201705f

  日期：2012.4.12

  The drug efflux pump P-glycoprotein (P-gp) has been shown to promote multidrug resistance (MDR) in tumors as well as to influence ADME properties of drug candidates. Here we synthesized and tested a series of benzophenone derivatives structurally analogous to propafenone-type inhibitors of P-gp. Some of the compounds showed ligand efficiency and lipophilic efficiency (LipE) values in the range of compounds which entered clinical trials as MDR modulators. Interestingly, although lipophilicity plays a dominant role for P-gp inhibitors, all compounds investigated showed LipE values below the threshold for promising drug candidates. Docking studies of selected analogues into a homology model of P-glycoprotein suggest that benzophenones show an interaction pattern similar to that previously identified for propafenone-type inhibitors.