5-N-tert-butoxycarbonylmethylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide | 1184301-87-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-N-tert-butoxycarbonylmethylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
• 英文别名: Substituted Benzamide Derivative, 47；tert-butyl N-[[4-methyl-3-[[(1R)-1-naphthalen-1-ylethyl]carbamoyl]phenyl]methyl]carbamate
• CAS: 1184301-87-8
• 化学式: C₂₆H₃₀N₂O₃
• 分子量: 418.536
• InChiKey: WFKRNMAWGCVMCU-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-N-tert-butoxycarbonylmethylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 以56%的产率得到(R)-5-(aminomethyl)-2-methyl-N-(1-(naphthalen-1-yl)ethyl)benzamide
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome−Coronavirus Papain-Like Protease

  摘要：

  We describe here the design, Synthesis, molecular modeling. and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells, Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC50 = 0.46 mu M; antiviral EC50 = 6 mu M). Interestingly. its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50 = 1.3 mu M) and the most potent SARS antiviral activity (EC50 = 5.2 mu M) in the series, We have carried our computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.

  DOI：

  10.1021/jm900611t
• 作为产物：
  描述：

  5-(叔丁氧基羰基氨基-甲基-2-甲基-苯甲酸 、 (R)-1-(1-萘基)乙胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以91%的产率得到5-N-tert-butoxycarbonylmethylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome−Coronavirus Papain-Like Protease

  摘要：

  We describe here the design, Synthesis, molecular modeling. and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells, Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC50 = 0.46 mu M; antiviral EC50 = 6 mu M). Interestingly. its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50 = 1.3 mu M) and the most potent SARS antiviral activity (EC50 = 5.2 mu M) in the series, We have carried our computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.

  DOI：

  10.1021/jm900611t

文献信息

• Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome−Coronavirus Papain-Like Protease
  作者：Arun K. Ghosh、Jun Takayama、Yoann Aubin、Kiira Ratia、Rima Chaudhuri、Yahira Baez、Katrina Sleeman、Melissa Coughlin、Daniel B. Nichols、Debbie C. Mulhearn、Bellur S. Prabhakar、Susan C. Baker、Michael E. Johnson、Andrew D. Mesecar

  DOI：10.1021/jm900611t

  日期：2009.8.27

  We describe here the design, Synthesis, molecular modeling. and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells, Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC50 = 0.46 mu M; antiviral EC50 = 6 mu M). Interestingly. its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50 = 1.3 mu M) and the most potent SARS antiviral activity (EC50 = 5.2 mu M) in the series, We have carried our computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.