1-[4-(4-acetylphenoxy)phenyl]-4-(2-chlorophenyl)butane-1,4-dione | 912675-35-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[4-(4-acetylphenoxy)phenyl]-4-(2-chlorophenyl)butane-1,4-dione
• CAS: 912675-35-5
• 化学式: C₂₄H₁₉ClO₄
• 分子量: 406.865
• InChiKey: AKVDDTFSLVBCNH-UHFFFAOYSA-N

物化性质

• 沸点：
  581.0±50.0 °C(predicted)
• 密度：
  1.242±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-(4-acetylphenoxy)phenyl]-4-(2-chlorophenyl)butane-1,4-dione 在 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[2-[4-(4-ethanoylphenoxy)phenyl]-5-(2-chlorophenyl)-1H-pyrrol-1-yl]-N-[amino(azanylidene)methyl]ethanamide
  参考文献：
  名称：

  Acylguanidines as Small-Molecule β-Secretase Inhibitors

  摘要：

  BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein to liberate A beta, which aggregates leading to plaque deposits implicated in Alzheimer's disease. We have identified small-molecule acylguanidine inhibitors of BACE1. Crystallographic studies show that these compounds form unique hydrogen-bonding interactions with the catalytic site aspartic acids and stabilize the protein in a flap-open conformation. Structure-based optimization led to the identification of potent analogs, such as 10d (BACE1 IC50 = 110 nM).

  DOI：

  10.1021/jm0607451
• 作为产物：
  描述：

  1-[4-(4-Acetylphenoxy)phenyl]-2-bromoethanone 、 邻氯苯乙酮 在 二乙胺 、 zinc(II) chloride 、 叔丁醇 作用下， 以 甲苯 为溶剂， 生成 1-[4-(4-acetylphenoxy)phenyl]-4-(2-chlorophenyl)butane-1,4-dione
  参考文献：
  名称：

  Acylguanidine inhibitors of β-secretase: Optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets

  摘要：

  Proteolytic cleavage of amyloid precursor protein by beta-secretase (BACE-1) and gamma-secretase leads to formation of beta-amyloid (A beta) a key component of amyloid plaques, which are considered the hallmark of Alzheimer's disease. Small molecule inhibitors of BACE-1 may reduce levels of A beta and thus have therapeutic potential for treating Alzheimer's disease. We recently reported the identification of a novel small molecule BACE-1 inhibitor N-[2-(2,5-diphenyl-pyrrol-1-yl)-acetyl]guanidine (3.a.1). We report here the initial hit-to-lead optimization of this hit and the SAR around the aryl groups occupying the S-1 and S-2' pockets leading to submicromolar BACE-1 inhibitors. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.010

文献信息

• Acylguanidine inhibitors of β-secretase: Optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets
  作者：Derek C. Cole、Joseph R. Stock、Rajiv Chopra、Rebecca Cowling、John W. Ellingboe、Kristi Y. Fan、Boyd L. Harrison、Yun Hu、Steve Jacobsen、Lee D. Jennings、Guixian Jin、Peter A. Lohse、Michael S. Malamas、Eric S. Manas、William J. Moore、Mary-Margaret O’Donnell、Andrea M. Olland、Albert J. Robichaud、Kristine Svenson、JunJun Wu、Eric Wagner、Jonathan Bard

  DOI：10.1016/j.bmcl.2007.12.010

  日期：2008.2

  Proteolytic cleavage of amyloid precursor protein by beta-secretase (BACE-1) and gamma-secretase leads to formation of beta-amyloid (A beta) a key component of amyloid plaques, which are considered the hallmark of Alzheimer's disease. Small molecule inhibitors of BACE-1 may reduce levels of A beta and thus have therapeutic potential for treating Alzheimer's disease. We recently reported the identification of a novel small molecule BACE-1 inhibitor N-[2-(2,5-diphenyl-pyrrol-1-yl)-acetyl]guanidine (3.a.1). We report here the initial hit-to-lead optimization of this hit and the SAR around the aryl groups occupying the S-1 and S-2' pockets leading to submicromolar BACE-1 inhibitors. (C) 2007 Elsevier Ltd. All rights reserved.
• Acylguanidines as Small-Molecule β-Secretase Inhibitors
  作者：Derek C. Cole、Eric S. Manas、Joseph R. Stock、Jeffrey S. Condon、Lee D. Jennings、Ann Aulabaugh、Rajiv Chopra、Rebecca Cowling、John W. Ellingboe、Kristi Y. Fan、Boyd L. Harrison、Yun Hu、Steve Jacobsen、Guixan Jin、Laura Lin、Frank E. Lovering、Michael S. Malamas、Mark L. Stahl、James Strand、Mohani N. Sukhdeo、Kristine Svenson、M. James Turner、Erik Wagner、Junjun Wu、Ping Zhou、Jonathan Bard

  DOI：10.1021/jm0607451

  日期：2006.10.1

  BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein to liberate A beta, which aggregates leading to plaque deposits implicated in Alzheimer's disease. We have identified small-molecule acylguanidine inhibitors of BACE1. Crystallographic studies show that these compounds form unique hydrogen-bonding interactions with the catalytic site aspartic acids and stabilize the protein in a flap-open conformation. Structure-based optimization led to the identification of potent analogs, such as 10d (BACE1 IC50 = 110 nM).