benzyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-2-(1-methyl-1H-indol-3-yl)ethyl]carbamate | 1366127-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: benzyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-2-(1-methyl-1H-indol-3-yl)ethyl]carbamate
• 英文别名: benzyl N-[(2S)-1-(cyanomethylamino)-3-(1-methylindol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 1366127-31-2
• 化学式: C₂₂H₂₂N₄O₃
• 分子量: 390.442
• InChiKey: DPCIYBLYQYDGFM-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  氨基乙腈硫酸氢盐 、 (2S)-2-{[(benzyloxy)carbonyl]amino}-3-(1-methyl-1H-indol-3-yl)propanoic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以58%的产率得到benzyl N-[(1S)-1-[(cyanomethyl)carbamoyl]-2-(1-methyl-1H-indol-3-yl)ethyl]carbamate
  参考文献：
  名称：

  Predicting and Improving the Membrane Permeability of Peptidic Small Molecules

  摘要：

  We evaluate experimentally and computationally the membrane permeability of matched sets of peptidic small molecules bearing natural or bioisosteric unnatural amino acids. We find that the intentional introduction of hydrogen bond acceptor-donor pairs in such molecules can improve membrane permeability while retaining or improving other favorable drug-like properties. We employ an all-atom force field based method to calculate changes in free energy associated with the transfer of the peptidic molecules from water to membrane. This computational method correctly predicts rank order experimental permeability trends within congeneric series and is much more predictive than calculations (e.g., clogP) that do not consider three-dimensional conformation.

  DOI：

  10.1021/jm201634q

文献信息

• Predicting and Improving the Membrane Permeability of Peptidic Small Molecules
  作者：Salma B. Rafi、Brian R. Hearn、Punitha Vedantham、Matthew P. Jacobson、Adam R. Renslo

  DOI：10.1021/jm201634q

  日期：2012.4.12

  We evaluate experimentally and computationally the membrane permeability of matched sets of peptidic small molecules bearing natural or bioisosteric unnatural amino acids. We find that the intentional introduction of hydrogen bond acceptor-donor pairs in such molecules can improve membrane permeability while retaining or improving other favorable drug-like properties. We employ an all-atom force field based method to calculate changes in free energy associated with the transfer of the peptidic molecules from water to membrane. This computational method correctly predicts rank order experimental permeability trends within congeneric series and is much more predictive than calculations (e.g., clogP) that do not consider three-dimensional conformation.