N-benzyl[(1S,2S)-2-methylcyclopropyl]methanamine | 935470-47-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyl[(1S,2S)-2-methylcyclopropyl]methanamine
• 英文别名: N-benzyl-1-[(1S,2S)-2-methylcyclopropyl]methanamine
• CAS: 935470-47-6
• 化学式: C₁₂H₁₇N
• 分子量: 175.274
• InChiKey: JNMRBVPZBLSNOC-CMPLNLGQSA-N

物化性质

• 沸点：
  252.6±9.0 °C(Predicted)
• 密度：
  0.971±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-benzyl[(1S,2S)-2-methylcyclopropyl]methanamine 在 palladium dihydroxide 、 bis(tri-tert-butylphosphine)palladium(0) potassium phosphate 、 氢气 、 三乙酰氧基硼氢化钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 为溶剂， 20.0~130.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 N-[(1S,2R)-2-azido-1-benzyl-3-fluoropropyl]-2-[(isopropylsulfonyl)(methyl)amino]-6-(methyl{[(1S,2S)-2-methylcyclopropyl]methyl}amino)isonicotinamide
  参考文献：
  名称：

  Discovery of Isonicotinamide Derived β-Secretase Inhibitors:  In Vivo Reduction of β-Amyloid

  摘要：

  beta-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides derived from traditional aspartyl protease transition state isostere inhibitors has been optimized to yield low nanomolar inhibitors with sufficient penetration across the blood-brain barrier to demonstrate beta-amyloid lowering in a murine model.

  DOI：

  10.1021/jm070272d
• 作为产物：
  描述：

  (1S,2S)-N-benzyl-2-methylcyclopropanecarboxamide 在 硼烷四氢呋喃络合物 作用下， 生成 N-benzyl[(1S,2S)-2-methylcyclopropyl]methanamine
  参考文献：
  名称：

  Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind β-secretase in a N-terminal 10s-loop down conformation

  摘要：

  A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-I inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P-3 which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.051

文献信息

• Discovery of Isonicotinamide Derived β-Secretase Inhibitors:  In Vivo Reduction of β-Amyloid
  作者：Matthew G. Stanton、Shaun R. Stauffer、Alison R. Gregro、Melissa Steinbeiser、Philippe Nantermet、Sethu Sankaranarayanan、Eric A. Price、Guoxin Wu、Ming-Chih Crouthamel、Joan Ellis、Ming-Tain Lai、Amy S. Espeseth、Xiao-Ping Shi、Lixia Jin、Dennis Colussi、Beth Pietrak、Qian Huang、Min Xu、Adam J. Simon、Samuel L. Graham、Joseph P. Vacca、Harold Selnick

  DOI：10.1021/jm070272d

  日期：2007.7.1

  beta-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides derived from traditional aspartyl protease transition state isostere inhibitors has been optimized to yield low nanomolar inhibitors with sufficient penetration across the blood-brain barrier to demonstrate beta-amyloid lowering in a murine model.
• Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind β-secretase in a N-terminal 10s-loop down conformation
  作者：Shaun R. Stauffer、Matthew G. Stanton、Alison R. Gregro、Melissa A. Steinbeiser、Jennifer R. Shaffer、Philippe G. Nantermet、James C. Barrow、Kenneth E. Rittle、Dennis Collusi、Amy S. Espeseth、Ming-Tain Lai、Beth L. Pietrak、M. Katharine Holloway、Georgia B. McGaughey、Sanjeev K. Munshi、Jerome H. Hochman、Adam J. Simon、Harold G. Selnick、Samuel L. Graham、Joseph P. Vacca

  DOI：10.1016/j.bmcl.2006.12.051

  日期：2007.3

  A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-I inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P-3 which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux. (c) 2007 Elsevier Ltd. All rights reserved.