(R)-N-(4-(叔丁基)苯基)-N-(2-(叔丁基氨基)-2-氧代-1-(吡啶-3-基)乙基)呋喃-2-甲酰胺 | 1417700-13-0

• 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: (R)-N-(4-(叔丁基)苯基)-N-(2-(叔丁基氨基)-2-氧代-1-(吡啶-3-基)乙基)呋喃-2-甲酰胺
• 英文名称: ML188
• 英文别名: (R)-N-(4-(tert-Butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide；N-[(1R)-2-(tert-butylamino)-2-oxo-1-pyridin-3-ylethyl]-N-(4-tert-butylphenyl)furan-2-carboxamide
• CAS: 1417700-13-0
• 化学式: C₂₆H₃₁N₃O₃
• 分子量: 433.55
• InChiKey: JXGIYKRRPGCLFV-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ML188 在 IA column 作用下， 以 甲醇 为溶剂， 生成 (R)-N-(4-(叔丁基)苯基)-N-(2-(叔丁基氨基)-2-氧代-1-(吡啶-3-基)乙基)呋喃-2-甲酰胺
  参考文献：
  名称：

  Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease

  摘要：

  A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S-1, S-1, and S-2 enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

  DOI：

  10.1021/jm301580n

文献信息

• Discovery, Synthesis, And Structure-Based Optimization of a Series of <i>N</i>-(<i>tert</i>-Butyl)-2-(<i>N</i>-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease
  作者：Jon Jacobs、Valerie Grum-Tokars、Ya Zhou、Mark Turlington、S. Adrian Saldanha、Peter Chase、Aimee Eggler、Eric S. Dawson、Yahira M. Baez-Santos、Sakshi Tomar、Anna M. Mielech、Susan C. Baker、Craig W. Lindsley、Peter Hodder、Andrew Mesecar、Shaun R. Stauffer

  DOI：10.1021/jm301580n

  日期：2013.1.24

  A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S-1, S-1, and S-2 enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.