N-((E)-(4S,11S)-4-[(R)-1-hydroxy-2-(3-isopropyl-benzylamino)-ethyl]-2,13-dioxo-11-phenyl-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-16-yl)-N-methyl-methanesulfonamide | 1385068-10-9

• 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: N-((E)-(4S,11S)-4-[(R)-1-hydroxy-2-(3-isopropyl-benzylamino)-ethyl]-2,13-dioxo-11-phenyl-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-16-yl)-N-methyl-methanesulfonamide
• 英文别名: N-[(4s,8e,11s)-4-[(1r)-1-Hydroxy-2-{[3-(Propan-2-Yl)benzyl]amino}ethyl]-2,13-Dioxo-11-Phenyl-6-Oxa-3,12-Diazabicyclo[12.3.1]octadeca-1(18),8,14,16-Tetraen-16-Yl]-N-Methylmethanesulfonamide；N-[(4S,8E,11S)-4-[(1R)-1-hydroxy-2-[(3-propan-2-ylphenyl)methylamino]ethyl]-2,13-dioxo-11-phenyl-6-oxa-3,12-diazabicyclo[12.3.1]octadeca-1(17),8,14(18),15-tetraen-16-yl]-N-methylmethanesulfonamide
• CAS: 1385068-10-9
• 化学式: C₃₅H₄₄N₄O₆S
• 分子量: 648.824
• InChiKey: XYJDOUBLYLOJJL-YNYOQIOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-异丙基苯酚 在 吡啶 、 三乙基硅烷 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 nickel(II) chloride hexahydrate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 N-((E)-(4S,11S)-4-[(R)-1-hydroxy-2-(3-isopropyl-benzylamino)-ethyl]-2,13-dioxo-11-phenyl-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-16-yl)-N-methyl-methanesulfonamide
  参考文献：
  名称：

  Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes

  摘要：

  A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC50 values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.039

文献信息

• Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes
  作者：Veronica Sandgren、Tatiana Agback、Per-Ola Johansson、Jimmy Lindberg、Ingemar Kvarnström、Bertil Samuelsson、Oscar Belda、Anders Dahlgren

  DOI：10.1016/j.bmc.2012.05.039

  日期：2012.7

  A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC50 values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed. (C) 2012 Elsevier Ltd. All rights reserved.