[2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetic acid | 912675-38-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: [2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetic acid
• 英文别名: 2-[2-(2-Chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetic acid
• CAS: 912675-38-8
• 化学式: C₂₁H₂₀ClNO₃
• 分子量: 369.848
• InChiKey: ADCKREJNEWQRQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  529.7±50.0 °C(predicted)
• 密度：
  1.21±0.1 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：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetic acid 在 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 生成 N-[(1Z)-amino[(3-hydroxypropyl)amino]methylidene]-2-[2-(2-chlorophenyl)-5-(4-propoxyphenyl)-1H-pyrrol-1-yl]acetamide
  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-丙氧基-苯基)-乙酮 在 溶剂黄146 、 二乙胺 、 zinc(II) chloride 作用下， 以 甲苯 、 叔丁醇 为溶剂， 生成 [2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetic acid
  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

文献信息

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

  DOI：10.1016/j.bmcl.2007.11.043

  日期：2008.1

  The proteolytic enzyme beta-secretase (BACE-1) produces amyloid beta(A beta) peptide, the primary constituent of neurofibrillary plaques, implicated in Alzheimer's disease, by cleavage of the amyloid precursor protein. A small molecule inhibitor of BACE-1, (diaminomethylene)-2,5-diphenyl-1H-pyrrole-1-acetamide (1, BACE-1 IC50 = 3.7 mu M), was recently described, representing a new small molecule lead. Initial SAR investigation demonstrated the potential of accessing the nearby S-3 and S-1' substrate binding pockets of the BACE-1 enzyme by building substituents off one of the phenyl substituents and guanidinyl functional group. We report here the optimization of guanidinyl functional group substituents on 1, leading to potent 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).