(2R,4S,5S)-2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid | 674787-22-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,4S,5S)-2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid
• CAS: 674787-22-5
• 化学式: C₂₆H₄₅NO₆Si
• 分子量: 495.732
• InChiKey: ZRULCYHHPMVALV-FSSWDIPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.38
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4S,5S)-2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid 在 N-甲基吗啉 、 盐酸 、 乙二胺四乙酸 、 1-羟基苯并三唑 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.33h， 生成 (S)-N-((1S,2S,4R)-1-Benzyl-2,7-dihydroxy-4-isobutylcarbamoyl-heptyl)-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
• 作为产物：
  描述：

  tert-butyl (1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamate 在 咪唑 、 sodium hydroxide 、 3> 、 lithium hexamethyldisilazane 、 儿萘酚硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 (2R,4S,5S)-2-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic 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

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.