tert-butyl N-[(2S,3S)-4-[amino(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate | 952196-23-5

• 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: tert-butyl N-[(2S,3S)-4-[amino(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 952196-23-5
• 化学式: C₁₉H₃₃N₃O₃
• 分子量: 351.489
• InChiKey: NBHRSHLWDGENSI-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 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：
  87.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S,3S)-4-[amino(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 (5S)-N'-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N'-(2-methylpropyl)-2-oxo-3-phenyl-1,3-oxazolidine-5-carbohydrazide
  参考文献：
  名称：

  Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2‘ Ligands in Pseudosymmetric Dipeptide Isosteres

  摘要：

  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.

  DOI：

  10.1021/jm070284z
• 作为产物：
  描述：

  benzyl N-[[(2S,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutyl]-(2-methylpropyl)amino]carbamate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 tert-butyl N-[(2S,3S)-4-[amino(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
  参考文献：
  名称：

  Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2‘ Ligands in Pseudosymmetric Dipeptide Isosteres

  摘要：

  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.

  DOI：

  10.1021/jm070284z

文献信息

• 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.