2-Dimethoxyphosphoryl-1-(1-phenylcyclopropyl)ethanone | 540731-27-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: 2-Dimethoxyphosphoryl-1-(1-phenylcyclopropyl)ethanone
• CAS: 540731-27-9
• 化学式: C₁₃H₁₇O₄P
• 分子量: 268.249
• InChiKey: LUJNYDHETMISCT-UHFFFAOYSA-N

物化性质

• 沸点：
  386.3±35.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Dimethoxyphosphoryl-1-(1-phenylcyclopropyl)ethanone 在 sodium tetrahydroborate 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 乙腈 为溶剂， 生成 ethyl 7-{(2R)-2-[(1E)-3-hydroxy-3-(1-phenylcyclopropyl)prop-1-enyl]-5-oxopyrrolidin-1-yl}heptanoate
  参考文献：
  名称：

  Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization

  摘要：

  A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP4 receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP4 versus the other EP prostanoid receptors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.063
• 作为产物：
  描述：

  1-苯基环丙烷-1-羧酸甲酯 、 甲基膦酸二甲酯 在 正丁基锂 作用下， 生成 2-Dimethoxyphosphoryl-1-(1-phenylcyclopropyl)ethanone
  参考文献：
  名称：

  Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization

  摘要：

  A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP4 receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP4 versus the other EP prostanoid receptors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.063

文献信息

• Method for treating ocular hypertension
  申请人：——

  公开号：US20040254230A1

  公开（公告）日：2004-12-16

  This invention relates to potent selective agonists of the EP 4 subtype of prostaglandin E2 receptors, their use or a formulation thereof in the treatment of glaucoma and other conditions that are related to elevated intraocular pressure in the eye of a patient. This invention also relates to the use of such compounds to provide a neuroprotective effect to the eye of mammalian species, particularly humans.

  本发明涉及到前列腺素E2受体EP4亚型的有效选择性激动剂，以及它们的使用或制剂在治疗青光眼和其他与患者眼内压升高有关的疾病中。本发明还涉及使用这些化合物为哺乳动物（尤其是人类）的眼提供神经保护作用。
• Discovery of a potent and selective agonist of the prostaglandin EP4 receptor
  作者：Xavier Billot、Anne Chateauneuf、Nathalie Chauret、Danielle Denis、Gillian Greig、Marie-Claude Mathieu、Kathleen M Metters、Deborah M Slipetz、Robert N Young

  DOI：10.1016/s0960-894x(03)00042-8

  日期：2003.3

  Analogues of PGE(2) wherein the hydroxycyclopentanone ring has been replaced by a lactam have been prepared and evaluated as ligands for the EP4 receptor. An optimized compound (19a) shows high potency and agonist efficacy at the EP4 receptor and is highly selective over the other seven known prostaglandin receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Lactams as prostanoid receptor ligands. Part 4: 2-Piperidones as selective EP4 receptor agonists
  作者：Todd R. Elworthy、Emma R. Brill、Christopher C. Caires、Woongki Kim、Leang K. Lach、Jahari Laurant Tracy、San-San Chiou

  DOI：10.1016/j.bmcl.2005.03.059

  日期：2005.5

  2-Piperidones were prepared bearing heptanoic acid or a thioether heptanoic acid at the I-position as well as appropriately substituted at the 6-position to mimic the structure of prostaglandins. The stereochemical purity at the 6-position was determined to be >= 95% ee for an advanced synthetic intermediate. The 2-piperidones were identified as potent agonists at the EP4 prostanoid receptor. They displayed a high affinity (K-i 5-130 nM) at EP4 and subtype selectivity. (c) 2005 Elsevier Ltd. All rights reserved.
• METHOD FOR TREATING OCULAR HYPERTENSION
  申请人：Merck & Co., Inc.

  公开号：EP1461026A2

  公开（公告）日：2004-09-29
• [EN] METHOD FOR TREATING OCULAR HYPERTENSION<br/>[FR] METHODE DE TRAITEMENT DE L'HYPERTENSION OCULAIRE
  申请人：MERCK & CO INC

  公开号：WO2003047513A2

  公开（公告）日：2003-06-12

  This invention relates to potent selective agonists of the EP4 subtype of prostaglandin E2 receptors, their use or a formulation thereof in the treatment of glaucoma and other conditions that are related to elevated intraocular pressure in the eye of a patient. This invention also relates to the use of such compounds to provide a neuroprotective effect to the eye of mammalian species, particularly humans.