福沙那韦杂质2 | 853904-81-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 福沙那韦杂质2
• 英文名称: tert-butyl N-[(2R,3R)-3-hydroxy-4-(2-methylpropylamino)-1-phenylbutan-2-yl]carbamate
• CAS: 853904-81-1
• 化学式: C₁₉H₃₂N₂O₃
• 分子量: 336.475
• InChiKey: NVEPLQDORJSXRO-IAGOWNOFSA-N

物化性质

• 沸点：
  484.7±45.0 °C(Predicted)
• 密度：
  1.039±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  福沙那韦杂质2 在 lithium hydroxide 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (R)-methyl 2-((R)-2-(3-((2R,3R)-3-(tert-butoxycarbonyl)-2-hydroxy-4-phenylbutyl)-3-isobutylureido)-4-methylpentanamido)-3-methylbutanoate
  参考文献：
  名称：

  Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase

  摘要：

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.

  DOI：

  10.1021/jm049566e
• 作为产物：
  描述：

  2-甲基-2-丙基[(2R)-1-苯基-3-丁烯-2-基]氨基甲酸酯 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 12.0h， 生成 福沙那韦杂质2
  参考文献：
  名称：

  Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase

  摘要：

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.

  DOI：

  10.1021/jm049566e

文献信息

• Pharmacokinetics of protease inhibitors and other drugs
  申请人：Mutz Mitchell W.

  公开号：US20080306098A1

  公开（公告）日：2008-12-11

  A method for modulating at least one pharmacokinetic property of a protease inhibitor upon administration to a host is provided. One administers to the host an effective amount of a bifunctional compound of less than about 5000 daltons comprising the protease inhibitor or an active derivative thereof and a pharmacokinetic modulating moiety. The pharmacokinetic modulating moiety binds to at least one intracellular protein. The bifunctional compound has at least one modulated pharmacokinetic property upon administration to the host as compared to a free drug control that comprises the protease inhibitor.

  提供了一种在给宿主施用蛋白酶抑制剂时调节至少一种药代动力学特性的方法。向宿主施用不超过约5000道尔顿的双功能化合物的有效量，该化合物包括蛋白酶抑制剂或其活性衍生物和药代动力学调节基团。药代动力学调节基团结合至少一个细胞内蛋白质。与包含蛋白酶抑制剂的自由药物对照相比，双功能化合物在向宿主施用后具有至少一个调节的药代动力学特性。
• WO2007/53792
  申请人：——

  公开号：——

  公开（公告）日：——
• Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase
  作者：Pancham Bakshi、Michael S. Wolfe

  DOI：10.1021/jm049566e

  日期：2004.12.1

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.