ethyl 2-(3,4-diphenethoxybenzyl)hexanoate | 1311392-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl 2-(3,4-diphenethoxybenzyl)hexanoate
• 英文别名: Ethyl 2-[[3,4-bis(2-phenylethoxy)phenyl]methyl]hexanoate
• CAS: 1311392-99-0
• 化学式: C₃₁H₃₈O₄
• 分子量: 474.64
• InChiKey: IXEANONSMSGSCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  35
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(3,4-diphenethoxybenzyl)hexanoate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.0h， 以84.5%的产率得到2-(3,4-diphenethoxybenzyl)hexanoic acid
  参考文献：
  名称：

  Discovery and Biological Evaluation of a Novel Class of Dual Microsomal Prostaglandin E₂ Synthase-1/5-lipoxygenase Inhibitors Based on 2-[(4,6-Diphenethoxypyrimidin-2-yl)thio]hexanoic Acid

  摘要：

  Various inflammatory diseases are associated with the excessive formation of leukotrienes (LTs) and prostaglandins (PGs). Herein, we present a novel class of dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1), key enzymes in the formation of LTs and PGE(2), respectively. On the basis of the structure of 2-[(4,6-diphenethoxypyrimidin-2-yl-)thio]hexanoic acid (1), we performed a detailed SAR analysis, and mechanistic studies were carried out to elucidate the mode of 5-LO inhibition. Interestingly, the pyrimidine ring including the thioether of 1 could be replaced by a simple benzyl or a benzylidene moiety yielding a novel series of bioactive 2-benzylidene- and 2-benzylhexanoic acids exemplified by 2-(2,3-diphenethoxybenzylidene)hexanoic acid, 29 (IC50 5-LO = 0.8 mu M; mPGES-1 = 1.1 mu M). Importantly, none of the novel bioactive derivatives strongly inhibited cyclooxygenase activities. Together, we provide novel promising lead compounds for the treatment of inflammatory diseases valuable for further investigations in vivo.

  DOI：

  10.1021/jm200092b
• 作为产物：
  描述：

  ethyl 2-(3,4-diphenethoxybenzylidene)hexanoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 24.0h， 生成 ethyl 2-(3,4-diphenethoxybenzyl)hexanoate
  参考文献：
  名称：

  Discovery and Biological Evaluation of a Novel Class of Dual Microsomal Prostaglandin E₂ Synthase-1/5-lipoxygenase Inhibitors Based on 2-[(4,6-Diphenethoxypyrimidin-2-yl)thio]hexanoic Acid

  摘要：

  Various inflammatory diseases are associated with the excessive formation of leukotrienes (LTs) and prostaglandins (PGs). Herein, we present a novel class of dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1), key enzymes in the formation of LTs and PGE(2), respectively. On the basis of the structure of 2-[(4,6-diphenethoxypyrimidin-2-yl-)thio]hexanoic acid (1), we performed a detailed SAR analysis, and mechanistic studies were carried out to elucidate the mode of 5-LO inhibition. Interestingly, the pyrimidine ring including the thioether of 1 could be replaced by a simple benzyl or a benzylidene moiety yielding a novel series of bioactive 2-benzylidene- and 2-benzylhexanoic acids exemplified by 2-(2,3-diphenethoxybenzylidene)hexanoic acid, 29 (IC50 5-LO = 0.8 mu M; mPGES-1 = 1.1 mu M). Importantly, none of the novel bioactive derivatives strongly inhibited cyclooxygenase activities. Together, we provide novel promising lead compounds for the treatment of inflammatory diseases valuable for further investigations in vivo.

  DOI：

  10.1021/jm200092b

文献信息

• SAR studies of acidic dual γ-secretase/PPARγ modulators
  作者：Martina Hieke、Julia Ness、Ramona Steri、Christine Greiner、Oliver Werz、Manfred Schubert-Zsilavecz、Sascha Weggen、Heiko Zettl

  DOI：10.1016/j.bmc.2011.08.003

  日期：2011.9

  A novel set of dual gamma-secretase/PPAR gamma modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act as dual gamma-secretase/PPAR gamma modulators in the low micromolar range. We have explored broad SAR and successfully improved the dual pharmacological activity and the selectivity profile against potential off-targets such as NOTCH and COX. Compound 17 showed an IC50 A beta 42 = 2.4 mu M and an EC50 PPAR gamma = 7.2 mu M and could be a valuable tool to further evaluate the concept of dual gamma-secretase/PPAR gamma modulators in animal models of Alzheimer's disease. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery and Biological Evaluation of a Novel Class of Dual Microsomal Prostaglandin E₂ Synthase-1/5-lipoxygenase Inhibitors Based on 2-[(4,6-Diphenethoxypyrimidin-2-yl)thio]hexanoic Acid
  作者：Martina Hieke、Christine Greiner、Michaela Dittrich、Felix Reisen、Gisbert Schneider、Manfred Schubert-Zsilavecz、Oliver Werz

  DOI：10.1021/jm200092b

  日期：2011.7.14

  Various inflammatory diseases are associated with the excessive formation of leukotrienes (LTs) and prostaglandins (PGs). Herein, we present a novel class of dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1), key enzymes in the formation of LTs and PGE(2), respectively. On the basis of the structure of 2-[(4,6-diphenethoxypyrimidin-2-yl-)thio]hexanoic acid (1), we performed a detailed SAR analysis, and mechanistic studies were carried out to elucidate the mode of 5-LO inhibition. Interestingly, the pyrimidine ring including the thioether of 1 could be replaced by a simple benzyl or a benzylidene moiety yielding a novel series of bioactive 2-benzylidene- and 2-benzylhexanoic acids exemplified by 2-(2,3-diphenethoxybenzylidene)hexanoic acid, 29 (IC50 5-LO = 0.8 mu M; mPGES-1 = 1.1 mu M). Importantly, none of the novel bioactive derivatives strongly inhibited cyclooxygenase activities. Together, we provide novel promising lead compounds for the treatment of inflammatory diseases valuable for further investigations in vivo.