[2-[[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]carbamoyl]-6-[[(1R)-1-phenylethyl]carbamoyl]pyridin-4-yl] phenylmethanesulfonate | 1236138-61-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [2-[[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]carbamoyl]-6-[[(1R)-1-phenylethyl]carbamoyl]pyridin-4-yl] phenylmethanesulfonate
• CAS: 1236138-61-6
• 化学式: C₃₉H₃₆N₈O₇S
• 分子量: 760.83
• InChiKey: UYJLDGJSVBEVDM-ZQISIDMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  55
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  227
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (2S,3S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutanoic acid 在 盐酸 、 1-羟基苯并三唑 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 [2-[[(2S,3S)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2H-tetrazol-5-yl)anilino]butan-2-yl]carbamoyl]-6-[[(1R)-1-phenylethyl]carbamoyl]pyridin-4-yl] phenylmethanesulfonate
  参考文献：
  名称：

  Structure–activity relationship study of BACE1 inhibitors possessing a chelidonic or 2,6-pyridinedicarboxylic scaffold at the P2 position

  摘要：

  We have previously reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. While these inhibitors exhibited potent activities in enzymatic and cellular assays (KMI-429 in particular inhibited A beta production in vivo), these inhibitors contained some natural amino acids that seemed to be required to improve enzymatic stability in vivo and permeability across the blood-brain barrier, so as to be practical drug. Recently, we synthesized non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold at the P-2 position. Herein we report the SAR study of BACE1 inhibitors possessing this heterocyclic scaffold, a chelidonic or 2,6-pyridinedicarboxylic moiety. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.007