KMI-708 | 1234204-07-9

• 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: KMI-708
• 英文别名: N-((2S,5S)-5-((S)-1-((1R,2S)-1-(3-(4,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl)phenylcarbamoyl)-1-hydroxy-3-phenylpropan-2-ylcarbamoyl)-3-methylbutylcarbamoyl)-2-amino-6-methyl-3-oxoheptyl)-2,5-dihydroxybenzamide；N-[(2S)-2-amino-3-[[(2S)-1-[[(2S)-1-[[(2S,3R)-3-hydroxy-4-oxo-4-[3-(5-oxo-4H-1,2,4-oxadiazol-3-yl)anilino]-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropyl]-2,5-dihydroxybenzamide
• CAS: 1234204-07-9
• 化学式: C₃₉H₄₈N₈O₁₀
• 分子量: 788.858
• InChiKey: GJFZGRKVQLFFMP-JONZOVCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  57
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  283
• 氢给体数：
  10
• 氢受体数：
  11

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 KMI-708
  参考文献：
  名称：

  Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1′ and P4 positions

  摘要：

  We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P-1' and P-4 positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P4 position with hydrogen bond accepting groups and acidic moieties at the P-1' position with less acidic and similar molecular-size moieties (carboxylic acid or tetrazole bioisosteres). These inhibitors exhibited improved BACE1 inhibitory activities and a thorough quantitative structure-activity relationship study was performed. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.032