N-((S)-2-amino-3-((S)-1-((S)-1-((2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(2-phenylpropan-2-ylamino)butan-2-ylamino)-4-methyl-1-oxopentan-2-ylamino)-3-methyl-1-oxobutan-2-ylamino)-3-oxopropyl)-5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamide | 1333494-83-9

• 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-((S)-2-amino-3-((S)-1-((S)-1-((2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(2-phenylpropan-2-ylamino)butan-2-ylamino)-4-methyl-1-oxopentan-2-ylamino)-3-methyl-1-oxobutan-2-ylamino)-3-oxopropyl)-5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamide
• 英文别名: KMI-1779；N-[(2S)-2-amino-3-[[(2S)-1-[[(2S)-1-[[(2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(2-phenylpropan-2-ylamino)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: 1333494-83-9
• 化学式: C₃₈H₅₁FN₈O₈
• 分子量: 766.87
• InChiKey: WIJNMWSAVOCDLS-ZYNCTLHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  55
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  250
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  Alpha,Alpha-二甲基苄胺 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 N-((S)-2-amino-3-((S)-1-((S)-1-((2S,3R)-3-hydroxy-4-oxo-1-phenyl-4-(2-phenylpropan-2-ylamino)butan-2-ylamino)-4-methyl-1-oxopentan-2-ylamino)-3-methyl-1-oxobutan-2-ylamino)-3-oxopropyl)-5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamide
  参考文献：
  名称：

  Structure-guided design and synthesis of P1′ position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors

  摘要：

  Previously, we reported potent pentapeptidic BACE1 inhibitors with the hydroxymethylcarbonyl isostere as a substrate transition-state mimic. To improve the in vitro potency, we further reported pentapeptidic inhibitors with carboxylic acid bioisosteres at the P-4 and P-1' positions. In the current study, we screened new P-1' position 1-phenylcycloalkylamine analogs to find non-acidic inhibitors that possess double-digit nanomolar range IC50 values. An extensive structure-activity relationship study was performed with various amine derivatives at the P-1' position. The most potent inhibitor of this pentapeptide series, KMI-1830, possessing 1-phenylcyclopentylamine at the P-1' position had an IC50 value of 11.6 nM against BACE1 in vitro enzymatic assay. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.002