N-[(1S,2S,4R)-1-(3,5-difluoro-phenoxymethyl)-5-(4-fluorophenylamino)-2-hydroxy-4-methoxy-pentyl]-5-(methanesulfonyl-N-methyl-amino)-N'-(1-(1R)-phenyl-ethyl)-isophthalamide | 1216935-32-8

• 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-[(1S,2S,4R)-1-(3,5-difluoro-phenoxymethyl)-5-(4-fluorophenylamino)-2-hydroxy-4-methoxy-pentyl]-5-(methanesulfonyl-N-methyl-amino)-N'-(1-(1R)-phenyl-ethyl)-isophthalamide
• 英文别名: 3-N-[(2S,3S,5R)-1-(3,5-difluorophenoxy)-6-(4-fluoroanilino)-3-hydroxy-5-methoxyhexan-2-yl]-5-[methyl(methylsulfonyl)amino]-1-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
• CAS: 1216935-32-8
• 化学式: C₃₇H₄₁F₃N₄O₇S
• 分子量: 742.816
• InChiKey: YDMGIZFKZZHPBQ-UTSDXBSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  52
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  、 3-[methyl(methylsulfonyl)amino]-5-((1R)-1-phenylethylaminocarbonyl)benzoate acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以40%的产率得到N-[(1S,2S,4R)-1-(3,5-difluoro-phenoxymethyl)-5-(4-fluorophenylamino)-2-hydroxy-4-methoxy-pentyl]-5-(methanesulfonyl-N-methyl-amino)-N'-(1-(1R)-phenyl-ethyl)-isophthalamide
  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.