5-(N-tert-butoxycarbonylmethyl)methylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide | 1184301-88-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(N-tert-butoxycarbonylmethyl)methylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide
• 英文别名: tert-butyl N-methyl-N-[[4-methyl-3-[[(1R)-1-naphthalen-1-ylethyl]carbamoyl]phenyl]methyl]carbamate
• CAS: 1184301-88-9
• 化学式: C₂₇H₃₂N₂O₃
• 分子量: 432.563
• InChiKey: MEFRLVGRFOYCSM-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(N-tert-butoxycarbonylmethyl)methylamino-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76%的产率得到GRL-0068S
  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-(((tert-butoxycarbonyl)(methyl)amino)methyl)-2-methylbenzoic acid 、 (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98%的产率得到5-(N-tert-butoxycarbonylmethyl)methylamino-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

• [EN] COMPOUNDS AND METHODS FOR TREATING RESPIRATORY DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE TRAITEMENT DES MALADIES RESPIRATOIRES
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2010022355A1

  公开（公告）日：2010-02-25

  Described herein are compounds and compositions, and methods for using the compounds and compositions, for treating respiratory diseases and illness, such as severe acute respiratory syndrome (SARS).