N-[(S)-4-((S)-1,2-dihydroxy-ethyl)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),14,16-trien-16-yl]-N-methyl-methanesulfonamide | 1385069-05-5

• 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-[(S)-4-((S)-1,2-dihydroxy-ethyl)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),14,16-trien-16-yl]-N-methyl-methanesulfonamide
• CAS: 1385069-05-5
• 化学式: C₁₉H₂₉N₃O₇S
• 分子量: 443.521
• InChiKey: HYOGTMBJBKFCSK-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.54
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  145.27
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-[(S)-4-((S)-1,2-dihydroxy-ethyl)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),14,16-trien-16-yl]-N-methyl-methanesulfonamide 在 二正丁基氧化锡 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 47.0h， 生成 N-[(S)-4-((R)-2-benzylamino-1-hydroxy-ethyl)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),14,16-trien-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
• 作为产物：
  描述：

  methyl 3-(but-3-en-1-ylcarbamoyl)-5-(n-methylmethyl-sulfonamido)benzoate 在 Hoveyda-Grubbs catalyst second generation 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 20.0~60.0 ℃ 、101.33 kPa 条件下， 反应 21.92h， 生成 N-[(S)-4-((S)-1,2-dihydroxy-ethyl)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),14,16-trien-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