4-(phenylacetyl)benzaldehyde | 345958-23-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 4-(phenylacetyl)benzaldehyde
• 英文别名: 4-(2-phenylacetyl)benzaldehyde
• CAS: 345958-23-8
• 化学式: C₁₅H₁₂O₂
• 分子量: 224.259
• InChiKey: MWPHJHDXMYKQRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(phenylacetyl)benzaldehyde 在 硫酸 、 palladium on activated charcoal 、 氢气 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 32.0h， 生成 1-(4-phenethylbenzyl)azetidine-3-carboxylic acid
  参考文献：
  名称：

  Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P₅) Agonist for the Potential Treatment of Neurodegenerative Disorders

  摘要：

  S1P(5) is one of S receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood brain barrier, where it maintains barrier integrity in in vitro models (j Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P(5) modulation due to the absence of tool molecules with suitable selectivity and drug-like properties. We recently reported that molecule A-971432 (Harris et al., 2010) (29 in this paper) is highly efficacious in reversing lipid accumulation and age-related cognitive decline in rats (Van der Kam, et al., AAIC 2014). Herein we describe the development of a series of selective S1P(5) agonists that led to the identification of compound 29, which is highly selective for S1P(5) and has excellent plasma and CNS exposure after oral dosing in preclinical species. To further support its suitability for in vivo studies of S1P(5) biology, we extensively characterized 29, including confirmation of its selectivity in pharmacodynamic assays of S1P(1). and S1P(3) function in rats. In addition, we found that 29 improves blood brain barrier integrity in an in vitro model and reverses age-related cognitive decline in mice. These results suggest that S1P(5) agonism is an innovative approach with potential benefit in neurodegenerative disorders involving lipid imbalance and/or compromised blood brain barrier such as Alzheimer's disease or multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.5b00928
• 作为产物：
  描述：

  Β-苯乙烯甲醚 在 bis(η3-allyl-μ-chloropalladium(II)) 盐酸 、 Tedicyp 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 4-(phenylacetyl)benzaldehyde
  参考文献：
  名称：

  四膦/钯配合物催化2-取代的烯醇醚与芳基溴的Heck反应

  摘要：

  顺式，顺式，顺式-1,2,3,4-四（二苯基膦甲基）环戊烷/ [PdCl（C 3 H 5）] 2有效催化β-取代的烯醇醚与芳基溴的Heck反应。在所有情况下，使用β-甲氧基苯乙烯，3-乙氧基丙烯腈或3-甲氧基丙烯酸甲酯，均能观察到这些烯醇醚的区域选择性α-芳基化作用，并且通常获得Z和E异构体的混合物，在许多情况下，经分离后生成单一的酮产物酸处理。该反应的立体选择性取决于空间和电子因素，有利于Z的更好的立体选择性在富含电子或空间上富集的芳基溴化物中观察到异构体。用富电子或空间拥挤的芳基溴化物比用贫电子的芳基溴化物能获得更好的收率。该观察结果表明，对于这些β-取代的烯醇醚，催化循环的限速步骤不是将芳基溴化物氧化加成到钯配合物中。

  DOI：

  10.1016/j.tetlet.2005.11.071

文献信息

• [EN] AGONISTS AND ANTAGONISTS OF THE S1P5 RECEPTOR, AND METHODS OF USES THEREOF<br/>[FR] AGONISTES ET ANTAGONISTES DU RÉCEPTEUR S1P5, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ABBOTT LAB

  公开号：WO2010093704A1

  公开（公告）日：2010-08-19

  Disclosed are compounds that are agonists or antagonists of the S1P5 receptor, compositions comprising said compounds, and methods of using said compounds and compositions. In certain embodiments, said compounds are 1-benzylazetidine-3-carboxylic acid derivatives. In certain embodiments, said methods relate to the treatment of neuropatic pain and/or a neurodegenerative disorder. In certain embodiments, said compounds may be used in combination with a second therapeutic agent.

  本文披露了作为S1P5受体激动剂或拮抗剂的化合物，包括含有这些化合物的组合物，以及使用这些化合物和组合物的方法。在某些实施例中，这些化合物是1-苄基氮杂环丙氨酸衍生物。在某些实施例中，这些方法涉及治疗神经痛和/或神经退行性疾病。在某些实施例中，这些化合物可以与第二治疗剂结合使用。
• Heck Reactions of α- or β-Substituted Enol Ethers with Aryl Bromides Catalysed by a Tetraphosphane/Palladium Complex – Direct Access to Acetophenone or 1-Arylpropanone Derivatives
  作者：Ahmed Battace、Marie Feuerstein、Mhamed Lemhadri、Touriya Zair、Henri Doucet、Maurice Santelli

  DOI：10.1002/ejoc.200700152

  日期：2007.7

  α-arylation of these enol ethers was observed in all cases, but mixtures of (Z) and (E) isomers were generally obtained, which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and electronic factors, and better stereoselectivities in favour of (Z) isomers were observed with electron-rich or sterically congested aryl bromides

  cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphanylmethyl)cyclopentane/[PdCl(C3H5)]2 有效地催化 α- 和 β- 取代的烯醇醚与芳基溴的 Heck 反应。1-苯基-1-(三甲基甲硅烷氧基)乙烯的芳基化直接导致2-芳基-1-苯基乙酮。在富电子、缺电子或空间拥挤的芳基溴化物中观察到类似的反应速率。与苄基异丙烯基醚的Heck反应得到异构体的混合物。然而，该混合物在水解后选择性地产生1-芳基丙酮。使用 β-甲氧基苯乙烯、3-乙氧基丙烯腈或 3-甲氧基丙烯酸甲酯，在所有情况下都观察到这些烯醇醚的区域选择性 α-芳基化，但通常会得到 (Z) 和 (E) 异构体的混合物，这在许多情况下产生了酸处理后的单一酮产品。该反应的立体选择性取决于空间和电子因素，并且在富电子或空间拥挤的芳基溴化物中观察到有利于 (Z) 异构体的更好的立体选
• Agonists and Antagonists of the S1P5 Receptor, and Methods of Use Thereof
  申请人：Harris Christopher M.

  公开号：US20100216762A1

  公开（公告）日：2010-08-26

  Disclosed are compounds that are agonists or antagonists of the S1P 5 receptor, compositions comprising said compounds, and methods of using said compounds and compositions. In certain embodiments, said compounds are 1-benzylazetidine-3-carboxylic acid derivatives. In certain embodiments, said methods relate to the treatment of neuropatic pain and/or a neurodegenerative disorder. In certain embodiments, said compounds may be used in combination with a second therapeutic agent.

  本发明涉及一种作为S1P5受体激动剂或拮抗剂的化合物，包括该化合物的组合物以及使用该化合物和组合物的方法。在某些实施例中，该化合物是1-苄基氮杂环丙氨酸衍生物。在某些实施例中，该方法涉及神经病性疼痛和/或神经退行性疾病的治疗。在某些实施例中，该化合物可以与第二种治疗药物联合使用。
• AGONISTS AND ANTAGONISTS OF THE SIP5 RECEPTOR, AND METHODS OF USES THEREOF
  申请人：Abbott Laboratories

  公开号：EP2395835A1

  公开（公告）日：2011-12-21
• Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P₅) Agonist for the Potential Treatment of Neurodegenerative Disorders
  作者：Adrian D. Hobson、Christopher M. Harris、Elizabeth L. van der Kam、Sean C. Turner、Ayome Abibi、Ana L. Aguirre、Peter Bousquet、Tegest Kebede、Donald B. Konopacki、Gary Gintant、Youngjae Kim、Kelly Larson、John W. Maull、Nigel S. Moore、Dan Shi、Anurupa Shrestha、Xiubo Tang、Peng Zhang、Kathy K. Sarris

  DOI：10.1021/acs.jmedchem.5b00928

  日期：2015.12.10

  S1P(5) is one of S receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood brain barrier, where it maintains barrier integrity in in vitro models (j Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P(5) modulation due to the absence of tool molecules with suitable selectivity and drug-like properties. We recently reported that molecule A-971432 (Harris et al., 2010) (29 in this paper) is highly efficacious in reversing lipid accumulation and age-related cognitive decline in rats (Van der Kam, et al., AAIC 2014). Herein we describe the development of a series of selective S1P(5) agonists that led to the identification of compound 29, which is highly selective for S1P(5) and has excellent plasma and CNS exposure after oral dosing in preclinical species. To further support its suitability for in vivo studies of S1P(5) biology, we extensively characterized 29, including confirmation of its selectivity in pharmacodynamic assays of S1P(1). and S1P(3) function in rats. In addition, we found that 29 improves blood brain barrier integrity in an in vitro model and reverses age-related cognitive decline in mice. These results suggest that S1P(5) agonism is an innovative approach with potential benefit in neurodegenerative disorders involving lipid imbalance and/or compromised blood brain barrier such as Alzheimer's disease or multiple sclerosis.