3-(2-cyclopropylethoxy)-6-(2-hydroxy-2-methylpropyl)phenanthrene-9,10-dione | 1191923-54-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 3-(2-cyclopropylethoxy)-6-(2-hydroxy-2-methylpropyl)phenanthrene-9,10-dione
• CAS: 1191923-54-2
• 化学式: C₂₃H₂₄O₄
• 分子量: 364.441
• InChiKey: OAXQNIRMSIKYRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,6-二溴-4-氟苯甲醛 、 3-(2-cyclopropylethoxy)-6-(2-hydroxy-2-methylpropyl)phenanthrene-9,10-dione 在 ammonium acetate 、 溶剂黄146 作用下， 反应 1.0h， 以85.3%的产率得到1-[9-(2-cyclopropylethoxy)-2-(2,6-dibromo-4-fluorophenyl)-1H-phenanthro[9,10-d]imidazol-9-yl]-2-methylpropan-2-ol
  参考文献：
  名称：

  A Practical Synthesis of m-Prostaglandin E Synthase-1 Inhibitor MK-7285

  摘要：

  A practical, kilogram-scale chromatography-free synthesis of mPGE synthase I inhibitor MK-7285 is described. The route features a convergent assembly of the core phenanthrene unit via amide-directed ortho-metalation and proximity-induced anionic cyclization, followed by imidazole synthesis and late-stage cyanation.

  DOI：

  10.1021/jo901798d
• 作为产物：
  描述：

  ethyl 2-(5-(2-cyclopropylethoxy)-3'-(2-hydroxy-2-methylpropyl)-[1,1'-biphenyl]-2-yl)-2-oxoacetate 在 水 、 sodium hydroxide 、 N,N'-羰基二咪唑 、 四氯化钛 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 3-(2-cyclopropylethoxy)-6-(2-hydroxy-2-methylpropyl)phenanthrene-9,10-dione
  参考文献：
  名称：

  Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors

  摘要：

  Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC50 of 0.20 and 0.14 mu M, respectively. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model at oral doses as low as 14 mg/kg. Both active and selective mPGES-1 inhibitors (26 and 44) have a relatively distinct pharmacokinetic profile and are suitable for clinical development. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.085

文献信息

• A Practical Synthesis of <i>m</i>-Prostaglandin E Synthase-1 Inhibitor MK-7285
  作者：Francis Gosselin、Stephen Lau、Christian Nadeau、Thao Trinh、Paul D. O’Shea、Ian W. Davies

  DOI：10.1021/jo901798d

  日期：2009.10.16

  A practical, kilogram-scale chromatography-free synthesis of mPGE synthase I inhibitor MK-7285 is described. The route features a convergent assembly of the core phenanthrene unit via amide-directed ortho-metalation and proximity-induced anionic cyclization, followed by imidazole synthesis and late-stage cyanation.
• Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors
  作者：André Giroux、Louise Boulet、Christine Brideau、Anh Chau、David Claveau、Bernard Côté、Diane Ethier、Richard Frenette、Marc Gagnon、Jocelyne Guay、Sébastien Guiral、Joseph Mancini、Evelyn Martins、Frédéric Massé、Nathalie Méthot、Denis Riendeau、Joel Rubin、Daigen Xu、Hongping Yu、Yves Ducharme、Richard W. Friesen

  DOI：10.1016/j.bmcl.2009.08.085

  日期：2009.10

  Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC50 of 0.20 and 0.14 mu M, respectively. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model at oral doses as low as 14 mg/kg. Both active and selective mPGES-1 inhibitors (26 and 44) have a relatively distinct pharmacokinetic profile and are suitable for clinical development. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.