2-(2,3-diphenethoxybenzyl)hexanoic acid | 1311392-74-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-(2,3-diphenethoxybenzyl)hexanoic acid
• 英文别名: 2-[[2,3-bis(2-phenylethoxy)phenyl]methyl]hexanoic acid
• CAS: 1311392-74-1
• 化学式: C₂₉H₃₄O₄
• 分子量: 446.587
• InChiKey: YDHGSYFSHRPUIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-膦酰己酸三乙酯 在 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 24.0h， 生成 2-(2,3-diphenethoxybenzyl)hexanoic acid
  参考文献：
  名称：

  SAR studies of acidic dual γ-secretase/PPARγ modulators

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.08.003

文献信息

• 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.