(5S*,6S*)-5,6-bis(4-methoxyphenyl)-1-octanoic acid | 107036-38-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (5S*,6S*)-5,6-bis(4-methoxyphenyl)-1-octanoic acid
• 英文别名: (5S*,6R*)-5,6-bis(4-methoxyphenyl)-1-octanoic acid
• CAS: 107036-38-4；120578-47-4；120578-48-5
• 化学式: C₂₂H₂₈O₄
• 分子量: 356.462
• InChiKey: RBCFZPZVWPIOEU-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.24
• 重原子数：
  26.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (5S*,6S*)-5,6-bis(4-methoxyphenyl)-1-octanoic acid 在 palladium on activated charcoal lithium aluminium tetrahydride 、 potassium tert-butylate 、 氢气 、 三溴化硼 、 sodium hydride 、 N,N'-dicyclohexyl-N-methylcarbodiimidium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 环己烷 为溶剂， 反应 16.0h， 生成 erythro-5,6-bis(4-hydroxyphenyl)-1-triethylene glycol monooctyl ether
  参考文献：
  名称：

  Hexestrol-linked cytotoxic agents: synthesis and binding affinity for estrogen receptors

  摘要：

  With the erythro-hexestrol derivative 2 as the starting material, a variety of cytotoxic linked hexestrol (HEX) compounds were prepared including the HEX-N-lost derivative 36, the HEX-(chloroethyl)nitrosourea 38, the HEX-cyclophosphamide 44, and the HEX-epoxide 68. Relative binding affinity to estradiol receptors were in the magnitude of 1%, similar to that of comparable diethylstilbestrol compounds. HEX derivatives with long polyether spacers (64, 65, 70, 71) showed no significant decrease in binding affinity in contrast to derivatives with other bulky side chains.

  DOI：

  10.1021/jm00127a023
• 作为产物：
  描述：

  tert-butyl 6-hydroxy-5,6-bis(4-methoxyphenyl)octanoate 在 palladium on activated charcoal 高氯酸 、 氢气 作用下， 以 溶剂黄146 为溶剂， 以45.5%的产率得到(5S*,6S*)-5,6-bis(4-methoxyphenyl)-1-octanoic acid
  参考文献：
  名称：

  Hexestrol-linked cytotoxic agents: synthesis and binding affinity for estrogen receptors

  摘要：

  With the erythro-hexestrol derivative 2 as the starting material, a variety of cytotoxic linked hexestrol (HEX) compounds were prepared including the HEX-N-lost derivative 36, the HEX-(chloroethyl)nitrosourea 38, the HEX-cyclophosphamide 44, and the HEX-epoxide 68. Relative binding affinity to estradiol receptors were in the magnitude of 1%, similar to that of comparable diethylstilbestrol compounds. HEX derivatives with long polyether spacers (64, 65, 70, 71) showed no significant decrease in binding affinity in contrast to derivatives with other bulky side chains.

  DOI：

  10.1021/jm00127a023

文献信息

• Estrogenic affinity labels: synthesis, irreversible receptor binding, and bioactivity of aziridine-substituted hexestrol derivatives
  作者：Jeffery A. Zablocki、John A. Katzenellenbogen、Kathryn E. Carlson、M. J. Norman、Benita S. Katzenellenbogen

  DOI：10.1021/jm00388a015

  日期：1987.5

  To develop an affinity label for the estrogen receptor that would be an estrogen agonist, rather than antagonist, we prepared several aziridine derivatives of the potent nonsteroidal estrogen hexestrol [3R,4S)-3,4-bis(4-hydroxyphenyl)hexane) bearing an aziridine function on the side chain. Three functional groups link the hexestrol ligand and the aziridine: a carbonyl group (ketone or ester), a thioether, or a methylene chain. The apparent competitive binding affinity of these derivatives for the estrogen receptor ranges from 1.8% to 25% that of estradiol, and most of them bind in a time-dependent, irreversible manner with the receptor, although the rate and efficiency of this binding vary widely, often with relatively small changes in structure. This is consistent with the irreversible attachment requiring a precise alignment of activating and reacting residues in the binding site of the receptor. The estrogenic and antiestrogenic activity of these aziridine derivatives was investigated in MCF-7 human breast cancer cells. Most of the compounds are agonists, with one being an antagonist. The derivative (6R,7S)-1-N-aziridinyl-6,7-bis(4-hydroxyphenyl)-5-nonanone (keto-nonestrol aziridine 3) appears to have the most ideal behavior of the estrogenic affinity labeling agents prepared: It is an agonist, and it binds to receptor irreversibly, efficiently, and quite rapidly.