toluene-4-sulfonic acid (S)-2-hydroxy-2-[(E)-(S)-16-(methanesulfonyl-methyl-amino)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-4-yl]-ethyl ester | 1385069-01-1

• 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: toluene-4-sulfonic acid (S)-2-hydroxy-2-[(E)-(S)-16-(methanesulfonyl-methyl-amino)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-4-yl]-ethyl ester
• CAS: 1385069-01-1
• 化学式: C₂₆H₃₃N₃O₉S₂
• 分子量: 595.695
• InChiKey: SKPOIEQHXIWJRL-CFFNCDDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.96
• 重原子数：
  40.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  168.41
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  toluene-4-sulfonic acid (S)-2-hydroxy-2-[(E)-(S)-16-(methanesulfonyl-methyl-amino)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-4-yl]-ethyl ester 、 3-(叔丁基)苄胺 以 乙醇 为溶剂， 反应 24.0h， 以34%的产率得到N-((E)-(S)-4-[(R)-2-(3-tert-butyl-benzylamino)-1-hydroxy-ethyl]-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(17),8,14(18),15-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
• 作为产物：
  描述：

  3-(甲氧基羰基)-5-(n-甲基甲基磺酰胺)苯甲酸 在 Hoveyda-Grubbs catalyst second generation 、 二正丁基氧化锡 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.92h， 生成 toluene-4-sulfonic acid (S)-2-hydroxy-2-[(E)-(S)-16-(methanesulfonyl-methyl-amino)-2,13-dioxo-6-oxa-3,12-diaza-bicyclo[12.3.1]octadeca-1(18),8,14,16-tetraen-4-yl]-ethyl ester
  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