N-[(1S,2S,4R)-4-((S)-1-benzylcarbamoyl-2-methyl-propylcarbamoyl)-1-(3,5-difluorophenoxymethyl)-2-hydroxy-4-methoxy-butyl]-5-(methanesulfonyl(methyl)amino)-N'-((R)-1-phenyl-ethyl)-isophthalamide | 1067651-20-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-[(1S,2S,4R)-4-((S)-1-benzylcarbamoyl-2-methyl-propylcarbamoyl)-1-(3,5-difluorophenoxymethyl)-2-hydroxy-4-methoxy-butyl]-5-(methanesulfonyl(methyl)amino)-N'-((R)-1-phenyl-ethyl)-isophthalamide
• 英文别名: N-[(1S,2S,4R)-4-((S)-1-benzylcarbamoyl-2-methyl-propylcarbamoyl)-1-(3,5-difluorophenoxymethyl)-2-hydroxy-4-methoxy-butyl]-5-(methanesulphonyl-methyl-amino)-N'-((R)-1-phenyl-ethyl)-isophthalamide；N-[4-(1-Benzylcarbamoyl-2-methyl-propylcarbamoyl)-1-(3,5-difluoro-phenoxymethyl)-2-hydroxy-4-methoxy-butyl]-5-(methanesulfonyl-methyl-amino)-N'-(1-phenylethyl)-isophthalamide；3-N-[(2S,3S,5R)-6-[[(2S)-1-(benzylamino)-3-methyl-1-oxobutan-2-yl]amino]-1-(3,5-difluorophenoxy)-3-hydroxy-5-methoxy-6-oxohexan-2-yl]-5-[methyl(methylsulfonyl)amino]-1-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
• CAS: 1067651-20-0
• 化学式: C₄₃H₅₁F₂N₅O₉S
• 分子量: 851.969
• InChiKey: IEIHXPJWOSDLBU-VWMOWEEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  60
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  201
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (2R,4S,5S)-5-amino-6-(3,5-difluoro-phenoxy)-4-hydroxy-2-methoxy-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-propyl)-amide 、 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 0.5h， 生成 N-[(1S,2S,4R)-4-((S)-1-benzylcarbamoyl-2-methyl-propylcarbamoyl)-1-(3,5-difluorophenoxymethyl)-2-hydroxy-4-methoxy-butyl]-5-(methanesulfonyl(methyl)amino)-N'-((R)-1-phenyl-ethyl)-isophthalamide
  参考文献：
  名称：

  Design and Synthesis of Potent and Selective BACE-1 Inhibitors

  摘要：

  Highly potent BACE-1 protease inhibitors have been developed from ill inhibitors containing a hydroxyethylene (HE) core displaying aryloxymethyl or benzyloxymethyl P1 side chain and a methoxy P1' side chain. The target molecules were synthesized in good overall yields from chiral carbohydrate starting materials. The inhibitors show high BACF-1 potency and good selectivity against cathepsin D, where the most potent inhibitor Furnishes BACE-1 Ki << 1 nM and displays > 1000-fold selectivity over cathepsin D.

  DOI：

  10.1021/jm901168f

文献信息

• Design and Synthesis of Potent and Selective BACE-1 Inhibitors
  作者：Catarina Björklund、Stefan Oscarson、Kurt Benkestock、Neera Borkakoti、Katarina Jansson、Jimmy Lindberg、Lotta Vrang、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1021/jm901168f

  日期：2010.2.25

  Highly potent BACE-1 protease inhibitors have been developed from ill inhibitors containing a hydroxyethylene (HE) core displaying aryloxymethyl or benzyloxymethyl P1 side chain and a methoxy P1' side chain. The target molecules were synthesized in good overall yields from chiral carbohydrate starting materials. The inhibitors show high BACF-1 potency and good selectivity against cathepsin D, where the most potent inhibitor Furnishes BACE-1 Ki << 1 nM and displays > 1000-fold selectivity over cathepsin D.