tert-butyl (4S,5S,7R)-7-[(allyloxy)carbonyl]-5-hydroxy-2-methyloctan-4-ylcarbamate | 897664-28-7

• 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: tert-butyl (4S,5S,7R)-7-[(allyloxy)carbonyl]-5-hydroxy-2-methyloctan-4-ylcarbamate
• 英文别名: prop-2-enyl (2R,4S,5S)-4-hydroxy-2,7-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]octanoate
• CAS: 897664-28-7
• 化学式: C₁₈H₃₃NO₅
• 分子量: 343.464
• InChiKey: PYKJELXIMBKCIR-ILXRZTDVSA-N

物化性质

• 沸点：
  452.3±45.0 °C(Predicted)
• 密度：
  1.023±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4S,5S,7R)-7-[(allyloxy)carbonyl]-5-hydroxy-2-methyloctan-4-ylcarbamate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 1,4-trans-4-({[(2R,4S,5S)-4-hydroxy-5-(N³,N³-dipropylisophthalamido)-2,7-dimethyloctanoyl]amino}methyl)cyclohexanecarboxylic acid
  参考文献：
  名称：

  Design, synthesis, and evaluation of Leu∗Ala hydroxyethylene-based non-peptide β-secretase (BACE) inhibitors

  摘要：

  With the aim of developing small molecular non-peptide P-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (< 600). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.024
• 作为产物：
  描述：

  (3R,5S)-5-[(1'S)-1-(N-Boc-amino)-3-methylbutyl]-3-methyl-dihydrofuran-2(3H)-one 在 lithium hydroxide 、 sodium dicarboxylate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 tert-butyl (4S,5S,7R)-7-[(allyloxy)carbonyl]-5-hydroxy-2-methyloctan-4-ylcarbamate
  参考文献：
  名称：

  Design, synthesis, and evaluation of Leu∗Ala hydroxyethylene-based non-peptide β-secretase (BACE) inhibitors

  摘要：

  With the aim of developing small molecular non-peptide P-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (< 600). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.024