2,5-diphenethoxybenzaldehyde | 353460-22-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,5-diphenethoxybenzaldehyde
• 英文别名: 2,5-bis-(2-phenyl-ethoxy)-benzaldehyde；2,5-Bis(2-phenylethoxy)benzaldehyde
• CAS: 353460-22-7
• 化学式: C₂₃H₂₂O₃
• 分子量: 346.426
• InChiKey: CRDRIYVAEQOXKU-UHFFFAOYSA-N

物化性质

• 沸点：
  527.6±50.0 °C(predicted)
• 密度：
  1.141±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,5-diphenethoxybenzaldehyde 在 lithium hydroxide monohydrate 、 水 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 31.0h， 生成 2-(2,5-diphenethoxybenzylidene)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：

  2,5-二羟基苯甲醛 、 苯乙醇 在 三苯基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以56%的产率得到2,5-diphenethoxybenzaldehyde
  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

• Thiazolidinecarboxyl acids
  申请人：——

  公开号：US20020037901A1

  公开（公告）日：2002-03-28

  5-Arylidene-4-oxo-2-thioxo-3-thiazolidinecarboxylic acids of formula I 1 in which the symbols R 1 , R 2 , A, A 1 and A 2 have the significance given in the description as medicaments for the treatment of cancer diseases.

  公式I1的5-芳基亚甲基-4-氧代-2-硫代-3-噻唑烷羧酸，其中符号R1，R2，A，A1和A2的意义在说明中给出，作为治疗癌症疾病的药物。
• 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.
• THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1189894A1

  公开（公告）日：2002-03-27
• US6506755B2
  申请人：——

  公开号：US6506755B2

  公开（公告）日：2003-01-14
• [EN] THIAZOLIDINE CARBOXYLIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER<br/>[FR] DERIVES D'ACIDE CARBOXYLIQUE THIAZOLIDINE ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：HOFFMANN LA ROCHE

  公开号：WO2001057006A1

  公开（公告）日：2001-08-09

  5-Arylidene-4-oxo-2-thioxo-3-thiazolidinecarboxylic acids of formula (I) in which the symbols R?1, R2, A, A1 and A2¿ have the significance given in the description as medicaments for the treatment of cancer diseases.