N-carbamimidoyl-2-[2-(6-methylnaphthalen-2-yl)-5-[4-(trifluoromethyl)phenyl]pyrrol-1-yl]acetamide | 905967-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-carbamimidoyl-2-[2-(6-methylnaphthalen-2-yl)-5-[4-(trifluoromethyl)phenyl]pyrrol-1-yl]acetamide
• CAS: 905967-84-2
• 化学式: C₂₅H₂₁F₃N₄O
• 分子量: 450.463
• InChiKey: SJVLEBCBDKRVSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  86.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  盐酸胍 、 2-(2-(6-methylnaphthalen-2-yl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrrol-1-yl)acetic acid 在 N,N'-羰基二咪唑 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-carbamimidoyl-2-[2-(6-methylnaphthalen-2-yl)-5-[4-(trifluoromethyl)phenyl]pyrrol-1-yl]acetamide
  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.