(S)-N-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-isobutylcarbamoyl-hept-6-enyl)-2-tert-butoxycarbonylamino-succinamic acid benzyl ester | 674787-25-8

• 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: (S)-N-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-isobutylcarbamoyl-hept-6-enyl)-2-tert-butoxycarbonylamino-succinamic acid benzyl ester
• 英文别名: benzyl (2S)-4-[[(2S,3S,5R)-3-hydroxy-5-(2-methylpropylcarbamoyl)-1-phenyloct-7-en-2-yl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 674787-25-8
• 化学式: C₃₅H₄₉N₃O₇
• 分子量: 623.79
• InChiKey: ZCNNSIOBTODWKG-RYTSNQFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  45
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-N-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-isobutylcarbamoyl-hept-6-enyl)-2-tert-butoxycarbonylamino-succinamic acid benzyl ester 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 乙二胺四乙酸 、 氢气 、 1-羟基苯并三唑 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 (S)-N-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-isobutylcarbamoyl-heptyl)-2-(3-methyl-butyrylamino)-succinamic acid
  参考文献：
  名称：

  Rational design and synthesis of selective BACE-1 inhibitors

  摘要：

  An effective approach for enhancing the selectivity of beta-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1' pocket of the enzyme. A series of low molecular weight ( < 600) compounds were synthesized with different moieties at the P1' position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.061
• 作为产物：
  描述：

  tert-butyl (1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamate 在 N-甲基吗啉 、 咪唑 、 盐酸 、 lithium hydroxide 、 乙二胺四乙酸 、 1-羟基苯并三唑 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 80.83h， 生成 (S)-N-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-isobutylcarbamoyl-hept-6-enyl)-2-tert-butoxycarbonylamino-succinamic acid benzyl ester
  参考文献：
  名称：

  Rational design and synthesis of selective BACE-1 inhibitors

  摘要：

  An effective approach for enhancing the selectivity of beta-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1' pocket of the enzyme. A series of low molecular weight ( < 600) compounds were synthesized with different moieties at the P1' position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.061

文献信息

• Rational design and synthesis of selective BACE-1 inhibitors
  作者：Stephen F. Brady、Satendra Singh、Ming-Chih Crouthamel、M.Katharine Holloway、Craig A. Coburn、Victor M. Garsky、Michael Bogusky、Michael W. Pennington、Joseph P. Vacca、Daria Hazuda、Ming-Tain Lai

  DOI：10.1016/j.bmcl.2003.11.061

  日期：2004.2

  An effective approach for enhancing the selectivity of beta-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1' pocket of the enzyme. A series of low molecular weight ( < 600) compounds were synthesized with different moieties at the P1' position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group. (C) 2003 Elsevier Ltd. All rights reserved.