(4-Fluoro-phenoxy)-acetic acid 1,4-dibenzyl-piperazin-2-ylmethyl ester | 148227-93-4

• 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: (4-Fluoro-phenoxy)-acetic acid 1,4-dibenzyl-piperazin-2-ylmethyl ester
• 英文别名: (1,4-Dibenzylpiperazin-2-yl)methyl 2-(4-fluorophenoxy)acetate
• CAS: 148227-93-4
• 化学式: C₂₇H₂₉FN₂O₃
• 分子量: 448.537
• InChiKey: FBMPPSWQJDRAMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-Fluoro-phenoxy)-acetic acid 1,4-dibenzyl-piperazin-2-ylmethyl ester 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 乙醇 、 苯 为溶剂， 25.0~40.0 ℃ 、275.79 kPa 条件下， 生成 (4-Fluoro-phenoxy)-acetic acid 1,4-bis-(3,4,5-trimethoxy-benzoyl)-piperazin-2-ylmethyl ester
  参考文献：
  名称：

  Design and modeling of new platelet-activating factor antagonists. 1. Synthesis and biological activity of 1,4-bis(3',4',5'-trimethoxybenzoyl)-2-[[(substituted carbonyl and carbamoyl)oxy]methyl]piperazines

  摘要：

  To further investigate our hypothesis on the structure of the platelet-activating factor (PAF) receptor, 35 compounds derived from 1,4-bis(3',4',5'-trimethoxybenzoyl)piperazine were synthesized and their in vitro antagonistic effect was measured. Substitution of the compounds in position 2, by ester or carbamate groups, giving increased steric hindrance and hydrophobicity, increased the platelet aggregation inhibitory activity from 2 muM (without substitution, compound 2) to 0.07 muM (compound 1h) arid gave a maximum displacement of [H-3]PAF from platelet membrane of 0.05 muM (compound 1k). It appears that the PAF antagonistic effect is only weakly enantiospecific, as observed in many cases including antagonists structurally related or not to PAF. 3D electrostatic potential maps (calculated at -10 kcal/mol) of such compounds revealed a double ''Cache-oreilles'' (ear-muffs) system. One of these systems has been previously described (distance between atoms generating negative wells, 11-14 angstrom). The second shorter ''Cache-oreilles'' (6-7 angstrom) system appears to be required for increased PAF antagonistic activity. This short distance between groups generating the negative wells is present in the gingkolides, a series of naturally occurring PAF antagonists. The present study indicates that the structure of the PAF receptor may be more complicated than our initial hypothesis and may be a tetrapolarized structure, with alternants of electropositive and hydrophobic areas. This modified hypothesis is in agreement with recent publications concerning PAF antagonists bearing a cationic moiety.

  DOI：

  10.1021/jm00060a006
• 作为产物：
  描述：

  2-(4-氟苯氧基)乙酰氯 、 1,4-dibenzyl-2-hydroxypiperazine 在 三乙胺 作用下， 以 苯 为溶剂， 以70%的产率得到(4-Fluoro-phenoxy)-acetic acid 1,4-dibenzyl-piperazin-2-ylmethyl ester
  参考文献：
  名称：

  Design and modeling of new platelet-activating factor antagonists. 1. Synthesis and biological activity of 1,4-bis(3',4',5'-trimethoxybenzoyl)-2-[[(substituted carbonyl and carbamoyl)oxy]methyl]piperazines

  摘要：

  To further investigate our hypothesis on the structure of the platelet-activating factor (PAF) receptor, 35 compounds derived from 1,4-bis(3',4',5'-trimethoxybenzoyl)piperazine were synthesized and their in vitro antagonistic effect was measured. Substitution of the compounds in position 2, by ester or carbamate groups, giving increased steric hindrance and hydrophobicity, increased the platelet aggregation inhibitory activity from 2 muM (without substitution, compound 2) to 0.07 muM (compound 1h) arid gave a maximum displacement of [H-3]PAF from platelet membrane of 0.05 muM (compound 1k). It appears that the PAF antagonistic effect is only weakly enantiospecific, as observed in many cases including antagonists structurally related or not to PAF. 3D electrostatic potential maps (calculated at -10 kcal/mol) of such compounds revealed a double ''Cache-oreilles'' (ear-muffs) system. One of these systems has been previously described (distance between atoms generating negative wells, 11-14 angstrom). The second shorter ''Cache-oreilles'' (6-7 angstrom) system appears to be required for increased PAF antagonistic activity. This short distance between groups generating the negative wells is present in the gingkolides, a series of naturally occurring PAF antagonists. The present study indicates that the structure of the PAF receptor may be more complicated than our initial hypothesis and may be a tetrapolarized structure, with alternants of electropositive and hydrophobic areas. This modified hypothesis is in agreement with recent publications concerning PAF antagonists bearing a cationic moiety.

  DOI：

  10.1021/jm00060a006

文献信息

• Design and modeling of new platelet-activating factor antagonists. 1. Synthesis and biological activity of 1,4-bis(3',4',5'-trimethoxybenzoyl)-2-[[(substituted carbonyl and carbamoyl)oxy]methyl]piperazines
  作者：Aazdine Lamouri、Francoise Heymans、Fabrice Tavet、Georges Dive、Jean Pierre Batt、Nicole Blavet、Pierre Braquet、Jean Jacques Godfroid

  DOI：10.1021/jm00060a006

  日期：1993.4

  To further investigate our hypothesis on the structure of the platelet-activating factor (PAF) receptor, 35 compounds derived from 1,4-bis(3',4',5'-trimethoxybenzoyl)piperazine were synthesized and their in vitro antagonistic effect was measured. Substitution of the compounds in position 2, by ester or carbamate groups, giving increased steric hindrance and hydrophobicity, increased the platelet aggregation inhibitory activity from 2 muM (without substitution, compound 2) to 0.07 muM (compound 1h) arid gave a maximum displacement of [H-3]PAF from platelet membrane of 0.05 muM (compound 1k). It appears that the PAF antagonistic effect is only weakly enantiospecific, as observed in many cases including antagonists structurally related or not to PAF. 3D electrostatic potential maps (calculated at -10 kcal/mol) of such compounds revealed a double ''Cache-oreilles'' (ear-muffs) system. One of these systems has been previously described (distance between atoms generating negative wells, 11-14 angstrom). The second shorter ''Cache-oreilles'' (6-7 angstrom) system appears to be required for increased PAF antagonistic activity. This short distance between groups generating the negative wells is present in the gingkolides, a series of naturally occurring PAF antagonists. The present study indicates that the structure of the PAF receptor may be more complicated than our initial hypothesis and may be a tetrapolarized structure, with alternants of electropositive and hydrophobic areas. This modified hypothesis is in agreement with recent publications concerning PAF antagonists bearing a cationic moiety.