2-(2-adamantan-1-yl-5-phenylpyrrol-1-yl)-N-(aminopyrazol-1-ylmethylene)acetamide | 912675-37-7

• 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-adamantan-1-yl-5-phenylpyrrol-1-yl)-N-(aminopyrazol-1-ylmethylene)acetamide
• 英文别名: 2-[2-(1-adamantyl)-5-phenylpyrrol-1-yl]-N-(pyrazole-1-carboximidoyl)acetamide
• CAS: 912675-37-7
• 化学式: C₂₆H₂₉N₅O
• 分子量: 427.549
• InChiKey: ATXUAZQVQXIWMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-adamantan-1-yl-5-phenylpyrrol-1-yl)-N-(aminopyrazol-1-ylmethylene)acetamide 、 3-氨基-1-丙醇 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以21.1 mg的产率得到N-[2-(2-adamantan-1-yl-5-phenylpyrrol-1-yl)acetyl]-N'-(3-hydroxypropyl)guanidine
  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-金刚烷基溴甲酮 在 sodium hydroxide 、 sodium hydride 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 43.0h， 生成 2-(2-adamantan-1-yl-5-phenylpyrrol-1-yl)-N-(aminopyrazol-1-ylmethylene)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

文献信息

• Azolylacylguanidines as beta-secretase inhibitors
  申请人：Cole Cecil Derek

  公开号：US20060183790A1

  公开（公告）日：2006-08-17

  The present invention provides an azolylacylquanidine compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.

  本发明提供了一种化合物，其化学式为I。本发明还提供了利用该化合物抑制β-分泌酶(BACE)、治疗β-淀粉样沉积和神经原纤维缠结的方法。
• AZOLYLACYLGUANIDINES AS beta-SECRETASE INHIBITORS
  申请人：Cole Derek Cecil

  公开号：US20080287424A1

  公开（公告）日：2008-11-20

  The present invention provides an azolylacylquanidine compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.

  本发明提供了一种式子为I的咪唑基酰基喹啉胺化合物。本发明还提供了使用该化合物的方法，以抑制β-分泌酶（BACE）并治疗β-淀粉样沉积和神经原纤维缠结。
• US7488832B2
  申请人：——

  公开号：US7488832B2

  公开（公告）日：2009-02-10
• 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).