KMI-1542 | 1234204-12-6

• 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: KMI-1542
• 英文别名: N-[(2S)-2-amino-3-[[(2S)-1-[[(2S)-1-[[(2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-[3-(2-sulfanylidene-3H-1,3,4-oxadiazol-5-yl)anilino]butan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropyl]-5-fluoro-2,4-dioxo-1H-pyrimidine-6-carboxamide
• CAS: 1234204-12-6
• 化学式: C₃₇H₄₅FN₁₀O₉S
• 分子量: 824.89
• InChiKey: FXMXRIBGRFQTFW-JYIQTIOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  58
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  316
• 氢给体数：
  10
• 氢受体数：
  13

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-1542
  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