3-((2R,3S)-3-((S)-2-((S)-2-((S)-2-amino-3-(2H-tetrazole-5-carboxamido)propanamido)-3-methylbutanamido)-4-methylpentanamido)-2-hydroxy-4-phenylbutanamido)benzoic acid

• 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: 3-((2R,3S)-3-((S)-2-((S)-2-((S)-2-amino-3-(2H-tetrazole-5-carboxamido)propanamido)-3-methylbutanamido)-4-methylpentanamido)-2-hydroxy-4-phenylbutanamido)benzoic acid
• 英文别名: 3-[[(2R,3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(2H-tetrazole-5-carbonylamino)propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-2-hydroxy-4-phenylbutanoyl]amino]benzoic acid
• 化学式: C₃₃H₄₄N₁₀O₈
• 分子量: 708.775
• InChiKey: FOEYBHHGUJYFBZ-WBAQKLHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  51
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  284
• 氢给体数：
  9
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  Fmoc-L-缬氨酸 、 Fmoc-L-亮氨酸 、 (S)-2-(Boc-氨)-3-(Fmoc-氨)丙酸 、 FMOC-3-氨基苯甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 3-((2R,3S)-3-((S)-2-((S)-2-((S)-2-amino-3-(2H-tetrazole-5-carboxamido)propanamido)-3-methylbutanamido)-4-methylpentanamido)-2-hydroxy-4-phenylbutanamido)benzoic acid
  参考文献：
  名称：

  Design and synthesis of highly active Alzheimer’s β-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability

  摘要：

  Recently, we reported potent and small-sized BACE1 inhibitors KMI-358 and KMI-370 in which the Glu residue is replaced by a beta-N-oxalyl-DAP (L-alpha,beta-diaminopropionyl) residue at the P-4 position. The beta-N-oxalyl-DAP group is important for enhancing BACE1 inhibitory activity, but these inhibitors isomerized to alpha-N-oxalyl-DAP derivatives in solvents. Hence, we used a tetrazole moiety as a bioisostere of the free carboxylic acid of the oxalyl group. KMI-420 and KMI-429, containing a tetrazole ring, showed improved stability and potent enzyme inhibitory activity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.09.090

文献信息

• Design and synthesis of highly active Alzheimer’s β-secretase (BACE1) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability
  作者：Tooru Kimura、Daisuke Shuto、Yoshio Hamada、Naoto Igawa、Soko Kasai、Ping Liu、Koushi Hidaka、Takashi Hamada、Yoshio Hayashi、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2004.09.090

  日期：2005.1

  Recently, we reported potent and small-sized BACE1 inhibitors KMI-358 and KMI-370 in which the Glu residue is replaced by a beta-N-oxalyl-DAP (L-alpha,beta-diaminopropionyl) residue at the P-4 position. The beta-N-oxalyl-DAP group is important for enhancing BACE1 inhibitory activity, but these inhibitors isomerized to alpha-N-oxalyl-DAP derivatives in solvents. Hence, we used a tetrazole moiety as a bioisostere of the free carboxylic acid of the oxalyl group. KMI-420 and KMI-429, containing a tetrazole ring, showed improved stability and potent enzyme inhibitory activity. (C) 2004 Elsevier Ltd. All rights reserved.