N-[(2S)-2-amino-3-[[(2S)-1-[[(2S)-1-[[(2S,3R)-4-(3,5-dinitroanilino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropyl]-2H-tetrazole-5-carboxamide | 941689-55-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[(2S)-2-amino-3-[[(2S)-1-[[(2S)-1-[[(2S,3R)-4-(3,5-dinitroanilino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropyl]-2H-tetrazole-5-carboxamide
• CAS: 941689-55-0
• 化学式: C₃₂H₄₂N₁₂O₁₀
• 分子量: 754.76
• InChiKey: FWESMVVJULJCLI-WBAQKLHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  54
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  338
• 氢给体数：
  8
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  在 盐酸 、 苯甲醚 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-[(2S)-2-amino-3-[[(2S)-1-[[(2S)-1-[[(2S,3R)-4-(3,5-dinitroanilino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropyl]-2H-tetrazole-5-carboxamide
  参考文献：
  名称：

  BACE1 inhibitors: Optimization by replacing the P1′ residue with non-acidic moiety

  摘要：

  Recently, we reported potent BACE1 inhibitors KMI-429, -684, and -574 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays, especially, KMI-429 was confirmed to significantly inhibit A beta production in vivo. However, acidic moieties at the P-4 and P-1' positions of KMI-compounds were thought to be unfavorable for membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P-4 position with other hydrogen bond acceptor groups, and these inhibitors exhibited improved BACE1 inhibitory activities in cultured cells. In this study, we replaced the acidic moieties at the P-1' position with non-acidic and low molecular sized moieties. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.058