1-[(2-hydroxynaphthalen-1-yl)[4-(2-morpholinoethoxy)phenyl]-methyl]piperidin-4-ol | 1335047-78-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-[(2-hydroxynaphthalen-1-yl)[4-(2-morpholinoethoxy)phenyl]-methyl]piperidin-4-ol
• 英文别名: 1-[(2-Hydroxynaphthalen-1-yl)-[4-(2-morpholin-4-ylethoxy)phenyl]methyl]piperidin-4-ol
• CAS: 1335047-78-3
• 化学式: C₂₈H₃₄N₂O₄
• 分子量: 462.589
• InChiKey: MQWPMAOHEXJDAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  65.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(2-氯乙基)吗啉盐酸盐 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 1-[(2-hydroxynaphthalen-1-yl)[4-(2-morpholinoethoxy)phenyl]-methyl]piperidin-4-ol
  参考文献：
  名称：

  Design, synthesis and bioevaluation of novel candidate selective estrogen receptor modulators

  摘要：

  In an systematic attempt to develop novel Selective Estrogen Receptor Modulators (SERMs), chiral 1-((4-(2-(dialkylamino)ethoxy)phenyl)(2-hydroxynaphthalen-1-yl)methyl)piperidin-4-ols were designed based on an accepted pharmacophore model. Simpler prototypes, viz. racemic 1-((2-hydroxynaphthalen-1-yl)arylmethyl)piperidin-4-ols, were first synthesized to develop kinetic resolution to pure enantiomers. Simultaneously, a series of racemic 1-((4-(2-(dialkylamino)ethoxy)phenyl)(2-hydroxynaphthalen-1-yl) methyl)piperidin-4-ols were evaluated against estrogen-responsive human MCF-7 breast cancer cells, but the compounds were found to be moderately active. The lack of potency could be due to the molecular bulk resulting in inadequate fit at the receptor. Subsequently, the molecular motif was modified to achiral 1-(4-(2-(dialkylamino)ethoxy)benzyl)naphthalen-2-ols by removing the piperidinol moiety. Bioevaluation of this new series of compounds displayed significantly enhanced cytotoxicity against MCF-7 cells. A representative compound for this series showed estrogen receptor alpha binding activity and the action is that of an antagonist. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.054

文献信息

• Design, synthesis and bioevaluation of novel candidate selective estrogen receptor modulators
  作者：Yogesh Yadav、Erin D. MacLean、Annyt Bhattacharyya、Virinder S. Parmar、Jan Balzarini、Christopher J. Barden、Catherine K.L. Too、Amitabh Jha

  DOI：10.1016/j.ejmech.2011.05.054

  日期：2011.9

  In an systematic attempt to develop novel Selective Estrogen Receptor Modulators (SERMs), chiral 1-((4-(2-(dialkylamino)ethoxy)phenyl)(2-hydroxynaphthalen-1-yl)methyl)piperidin-4-ols were designed based on an accepted pharmacophore model. Simpler prototypes, viz. racemic 1-((2-hydroxynaphthalen-1-yl)arylmethyl)piperidin-4-ols, were first synthesized to develop kinetic resolution to pure enantiomers. Simultaneously, a series of racemic 1-((4-(2-(dialkylamino)ethoxy)phenyl)(2-hydroxynaphthalen-1-yl) methyl)piperidin-4-ols were evaluated against estrogen-responsive human MCF-7 breast cancer cells, but the compounds were found to be moderately active. The lack of potency could be due to the molecular bulk resulting in inadequate fit at the receptor. Subsequently, the molecular motif was modified to achiral 1-(4-(2-(dialkylamino)ethoxy)benzyl)naphthalen-2-ols by removing the piperidinol moiety. Bioevaluation of this new series of compounds displayed significantly enhanced cytotoxicity against MCF-7 cells. A representative compound for this series showed estrogen receptor alpha binding activity and the action is that of an antagonist. (C) 2011 Elsevier Masson SAS. All rights reserved.