2-phenyl(4-pyrrolidinylethoxyphenyl)ethan-1-one | 14036-32-9

• 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: 2-phenyl(4-pyrrolidinylethoxyphenyl)ethan-1-one
• 英文别名: ω-Phenyl-4-(2-pyrrolidino-ethoxy>-acetophenon；2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-ethanone；2-Phenyl-1-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)ethanone；2-phenyl-1-[4-(2-pyrrolidin-1-ylethoxy)phenyl]ethanone
• CAS: 14036-32-9
• 化学式: C₂₀H₂₃NO₂
• 分子量: 309.408
• InChiKey: JYKNTMKCVVRJJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 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：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-phenyl(4-pyrrolidinylethoxyphenyl)ethan-1-one 、 苯丙酮 在 四氯化钛 、 锌 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以74%的产率得到1-benzyl-2-phenyl[4-(pyrrolidinylethoxy)phenyl]but-1-ene
  参考文献：
  名称：

  Flexible Estrogen Receptor Modulators:  Design, Synthesis, and Antagonistic Effects in Human MCF-7 Breast Cancer Cells

  摘要：

  Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds ' potential interactions with specific residues within the human estrogen receptor a ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.

  DOI：

  10.1021/jm001119l
• 作为产物：
  描述：

  苄基-4-羟基苯酮 、 N-(2-氯乙基)吡咯烷盐酸盐 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以94%的产率得到2-phenyl(4-pyrrolidinylethoxyphenyl)ethan-1-one
  参考文献：
  名称：

  Flexible Estrogen Receptor Modulators:  Design, Synthesis, and Antagonistic Effects in Human MCF-7 Breast Cancer Cells

  摘要：

  Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds ' potential interactions with specific residues within the human estrogen receptor a ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.

  DOI：

  10.1021/jm001119l

文献信息

• Erythro-1,2,3-Triphenyl-1-pentanon-Derivate sowie Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
  申请人：Klinge Pharma GmbH

  公开号：EP0065692A1

  公开（公告）日：1982-12-01

  Erythro-1,2,3-Triphenyl-1-pentanone der allgemeinen Formel 1 in der R1 eine Dimethylamino-, Diethylamino-, Piperidin-1-yl-oder Pyrrolidin-1-yl-gruppe sein kann und R2 ein Wasserstoffatom, eine Methoxy- oder Hydroxygruppe darstellt und deren therapeutisch verträgliche Salze, besitzen eine ausgeprägte antiestrogene Wirkung und sind geeignet zur Behandlung hormonabhängiger Tumore. Sie können dadurch hergestellt werden, daß man 1,2-Diphenylethanone der allgemeinen Formel 2 in der R' die in der allgemeinen Formel 1 angegebene Bedeutung besitzt und R2 ein Wasserstoffatom oder eine Methoxygruppe darstellt, in wasserfreiem Dimethylformamid mit Natriumhydrid reagieren läßt, nach Umsetzung mit 1-Chlor-1-phenylpropan aus dem Reaktionsprodukt die Erythroform isoliert und gegebenenfalls die Hydroxygruppe durch selektive Spaltung mit Bromwasserstoff aus der Methoxygruppe freisetzt.

  通式 1 的赤式-1,2,3-三苯基-1-戊酮 其中 R1 可以是二甲基氨基、二乙基氨基、哌啶-1-基或吡咯烷-1-基，R2 是氢原子、甲氧基或羟基，以及它们的治疗用盐类，具有明显的抗雌激素作用，适用于治疗激素依赖性肿瘤。 它们可以通过通式 2 的 1,2-二苯基乙酮反应制备 其中 R'具有通式 1 中给出的含义，R2 代表氢原子或甲氧基，在无水二甲基甲酰胺中与氢化钠反应，在与 1-氯-1-苯基丙烷反应后，从反应产物中分离出赤式，并在适当的情况下，用溴化氢选择性裂解，从甲氧基中释放出羟基。
• SCHICKANEDER, H.;LOESER, R.
  作者：SCHICKANEDER, H.、LOESER, R.

  DOI：——

  日期：——
• US4764533A
  申请人：——

  公开号：US4764533A

  公开（公告）日：1988-08-16
• Flexible Estrogen Receptor Modulators:  Design, Synthesis, and Antagonistic Effects in Human MCF-7 Breast Cancer Cells
  作者：Mary J. Meegan、Rosario B. Hughes、David G. Lloyd、D. Clive Williams、Daniela M. Zisterer

  DOI：10.1021/jm001119l

  日期：2001.3.1

  Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds ' potential interactions with specific residues within the human estrogen receptor a ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.