N-[5-(5S)-azido-6-(3,5-difluoro-phenoxy)-2-(2R)-methoxy-4-(4S)-(4-methoxy-benzyloxy)-hexyl]-N-benzyl-2-nitro-benzenesulfonamide | 1216935-03-3

• 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-[5-(5S)-azido-6-(3,5-difluoro-phenoxy)-2-(2R)-methoxy-4-(4S)-(4-methoxy-benzyloxy)-hexyl]-N-benzyl-2-nitro-benzenesulfonamide
• 英文别名: N-[(2R,4S,5S)-5-azido-6-(3,5-difluorophenoxy)-2-methoxy-4-[(4-methoxyphenyl)methoxy]hexyl]-N-benzyl-2-nitrobenzenesulfonamide
• CAS: 1216935-03-3
• 化学式: C₃₄H₃₅F₂N₅O₈S
• 分子量: 711.743
• InChiKey: CEEJKLKIFXODDI-DNNYKULVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  143
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  N-[5-(5S)-azido-6-(3,5-difluoro-phenoxy)-2-(2R)-methoxy-4-(4S)-(4-methoxy-benzyloxy)-hexyl]-N-benzyl-2-nitro-benzenesulfonamide 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 水 为溶剂， 以64%的产率得到N-[5-(5S)-azido-6-(3,5-difluoro-phenoxy)-4-(4S)-hydroxy-2-(2R)-methoxy-hexyl]-N-benzyl-2-nitro-benzenesulfonamide
  参考文献：
  名称：

  P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core

  摘要：

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.10.041
• 作为产物：
  描述：

  (2R,4S,5S)-5-azido-6-(3,5-difluoro-phenoxy)-2-methoxy-4-(4-methoxy-benzyloxy)-hexan-1-ol 、 N-苄基-2-硝基苯磺酰胺 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以61%的产率得到N-[5-(5S)-azido-6-(3,5-difluoro-phenoxy)-2-(2R)-methoxy-4-(4S)-(4-methoxy-benzyloxy)-hexyl]-N-benzyl-2-nitro-benzenesulfonamide
  参考文献：
  名称：

  P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core

  摘要：

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.10.041

文献信息

• P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
  作者：Jenny Adrian Meredith、Catarina Björklund、Hans Adolfsson、Katarina Jansson、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.ejmech.2009.10.041

  日期：2010.2

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.