3-[[Amino-[[2-[2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetyl]amino]methylidene]amino]propanamide | 905970-14-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-[[Amino-[[2-[2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetyl]amino]methylidene]amino]propanamide
• CAS: 905970-14-1
• 化学式: C₂₅H₂₈ClN₅O₃
• 分子量: 481.982
• InChiKey: KJOSSSCOHUKPCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-[2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]-N-(pyrazole-1-carboximidoyl)acetamide 、 3-氨基丙酰胺 在 N,N-二异丙基乙胺 作用下， 反应 16.0h， 生成 3-[[Amino-[[2-[2-(2-chlorophenyl)-5-(4-propoxyphenyl)pyrrol-1-yl]acetyl]amino]methylidene]amino]propanamide
  参考文献：
  名称：

  Acylguanidine inhibitors of β-secretase: Optimization of the pyrrole ring substituents extending into the substrate binding pocket

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2007.11.043

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.