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