(S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺 | 192726-05-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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
• 中文名称: (S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺
• 中文别名: 洛匹那韦EP杂质A
• 英文名称: (2S)-N-[(2S,4S,5S)-5-amino-4-hydroxy-1,6-diphenylhexane-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
• 英文别名: (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(2-oxotetrahydropyrimidin-2-yl)-3-methylbutanoyl)amino-1,6-diphenylhexane；(2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane；(S)-N-[(2S,4S,5S)-5-Amino-4-hydroxy-1,6-diphenylhexan-2-YL]-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-YL)butanamide；(2S)-N-[(2S,4S,5S)-5-amino-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
• CAS: 192726-05-9
• 化学式: C₂₇H₃₈N₄O₃
• 分子量: 466.624
• InChiKey: PSXHIAOZPOGORP-QORCZRPOSA-N

物化性质

• 沸点：
  762.2±60.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺 、 (2,6-二甲基苯氧基)乙酰氯 在 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 洛匹那韦
  参考文献：
  名称：

  Synthesis and Characterization of Novel Analogues of Lopinavir

  摘要：

  这项工作描述了四种洛匹那韦新颖类似物的鉴定、起源、合成、表征和控制，即洛匹那韦的亮氨酸类似物、异亮氨酸类似物、甲基类似物和二羟基类似物。

  DOI：

  10.14233/ajchem.2021.22954
• 作为产物：
  描述：

  (2S)-(1-四氢嘧啶-2-酮)-3-甲基丁酸 在 5%-palladium/activated carbon 、 甲酸铵 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 8.0h， 生成 (S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺
  参考文献：
  名称：

  Synthesis and Characterization of Novel Analogues of Lopinavir

  摘要：

  这项工作描述了四种洛匹那韦新颖类似物的鉴定、起源、合成、表征和控制，即洛匹那韦的亮氨酸类似物、异亮氨酸类似物、甲基类似物和二羟基类似物。

  DOI：

  10.14233/ajchem.2021.22954

文献信息

• Retroviral protease inhibiting compounds
  申请人：Abbott Laboratories

  公开号：EP1170289A2

  公开（公告）日：2002-01-09

  A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.

  披露了一种包含公式（II）取代基的化合物，作为一种HIV蛋白酶抑制剂。还披露了用于制造此类化合物的中间体以及制造此类中间体的过程。
• Processes and intermediates for preparing retroviral protease inhibitors
  申请人：Abbott Laboratories

  公开号：US06372905B1

  公开（公告）日：2002-04-16

  The instant invention provides processes and intermediates employed in the synthesis of ((2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)-amino-3-hydroxy-5-(2S-(1-tetrahydropyrimid-2-onyl)-3-methyl-butanoyl)amino-1,6-diphenylhexane and analogs thereof.

  本发明提供了用于合成((2S,3S,5S)-2-(2,6-二甲基苯氧乙酰)氨基-3-羟基-5-(2S-(1-四氢嘧啶-2-酰基)-3-甲基丁酰基)氨基-1,6-二苯基己烷及其类似物的过程和中间体。
• Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2‘ Ligands in Pseudosymmetric Dipeptide Isosteres
  作者：G. S. Kiran Kumar Reddy、Akbar Ali、Madhavi N. L. Nalam、Saima Ghafoor Anjum、Hong Cao、Robin S. Nathans、Celia A. Schiffer、Tariq M. Rana

  DOI：10.1021/jm070284z

  日期：2007.9.1

  A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure -activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
• Synthesis and Characterization of Novel Analogues of Lopinavir
  作者：Peketi Rajesh Reddy、Sivanadh Musunuri、D. Ramasekhara Reddy、V. Subrahmanyam Chittala、P.V.N.S. Murthy、K. Krishnamohan

  DOI：10.14233/ajchem.2021.22954

  日期：——

  The present work describes the identification, origin, synthesis, characterization and control of four novel analogues of lopinavir viz. leucine analogue of lopinavir, isoleucine analogue of lopinavir, methyl analogue of lopinavir and dihydroxy analogue of lopinavir.

  这项工作描述了四种洛匹那韦新颖类似物的鉴定、起源、合成、表征和控制，即洛匹那韦的亮氨酸类似物、异亮氨酸类似物、甲基类似物和二羟基类似物。