N-[2-(tert-butylamino)-2-oxo-1-thiophen-3-ylethyl]-N-cyclopropyl-1H-indazole-3-carboxamide | 1417700-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: N-[2-(tert-butylamino)-2-oxo-1-thiophen-3-ylethyl]-N-cyclopropyl-1H-indazole-3-carboxamide
• CAS: 1417700-74-3
• 化学式: C₂₁H₂₄N₄O₂S
• 分子量: 396.513
• InChiKey: AUYIXQUHFCFOTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-噻吩甲醛 、 异氰酸叔丁酯 、 吲唑-3-羧酸 、 环丙胺 以 甲醇 为溶剂， 反应 16.0h， 生成 N-[2-(tert-butylamino)-2-oxo-1-thiophen-3-ylethyl]-N-cyclopropyl-1H-indazole-3-carboxamide
  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.