propane-1-sulfonic acid {(S)-4-[(R)-1-hydroxy-2-(3-isopropylbenzylamino)ethyl]-2-oxo-11-oxa-3,16-diazatricyclo[15.3.1.1*6,10*]docosa-1(21),6,8,10(22),17,19-hexaen-19-yl}-methyl-amide | 900798-17-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: propane-1-sulfonic acid {(S)-4-[(R)-1-hydroxy-2-(3-isopropylbenzylamino)ethyl]-2-oxo-11-oxa-3,16-diazatricyclo[15.3.1.1*6,10*]docosa-1(21),6,8,10(22),17,19-hexaen-19-yl}-methyl-amide
• 英文别名: N-[(4S)-4-[(1R)-1-hydroxy-2-[(3-propan-2-ylphenyl)methylamino]ethyl]-2-oxo-11-oxa-3,16-diazatricyclo[15.3.1.16,10]docosa-1(21),6(22),7,9,17,19-hexaen-19-yl]-N-methylpropane-1-sulfonamide
• CAS: 900798-17-6
• 化学式: C₃₅H₄₈N₄O₅S
• 分子量: 636.856
• InChiKey: HWLAFZXKYIUVHI-SZAHLOSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 1% Pd/C 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 propane-1-sulfonic acid {(S)-4-[(R)-1-hydroxy-2-(3-isopropylbenzylamino)ethyl]-2-oxo-11-oxa-3,16-diazatricyclo[15.3.1.1*6,10*]docosa-1(21),6,8,10(22),17,19-hexaen-19-yl}-methyl-amide
  参考文献：
  名称：

  Macrocyclic BACE-1 inhibitors acutely reduce Aβ in brain after po application

  摘要：

  A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI-MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Ab in human APP-wildtype transgenic (APP51/16) mice after oral administration. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.092