N-(2-(1H-pyrazol-1-yl)ethyl)-2-(4-(4-cyano-3-methylphenoxy)phenyl)-N-ethylacetamide

• 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: N-(2-(1H-pyrazol-1-yl)ethyl)-2-(4-(4-cyano-3-methylphenoxy)phenyl)-N-ethylacetamide
• 英文别名: 2-[4-(4-cyano-3-methylphenoxy)phenyl]-N-ethyl-N-[2-(1H-pyrazol-1-yl)ethyl]acetamide；2-[4-(4-cyano-3-methylphenoxy)phenyl]-N-ethyl-N-(2-pyrazol-1-ylethyl)acetamide
• 化学式: C₂₃H₂₄N₄O₂
• 分子量: 388.469
• InChiKey: ABKHTUJKHPJZLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  71.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴-2-甲基苯腈 在 copper(l) iodide 、 草酰氯 、 N,N-二甲基甘氨酸盐酸盐 、 caesium carbonate 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 甲醇 、 氘代氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 N-(2-(1H-pyrazol-1-yl)ethyl)-2-(4-(4-cyano-3-methylphenoxy)phenyl)-N-ethylacetamide
  参考文献：
  名称：

  Rapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiL_X)

  摘要：

  A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low affinity to their target. Herein, we describe an analysis using X-ray crystallography of a diverse library of compounds prepared using microscale parallel synthesis. This approach yielded an 8-fold increase in affinity and detailed structural information for the resulting complex, providing an efficient and broadly applicable approach to early fragment development.

  DOI：

  10.1021/acs.jmedchem.0c00111

文献信息

• Rapid Elaboration of Fragments into Leads by X-ray Crystallographic Screening of Parallel Chemical Libraries (REFiL_X)
  作者：Matthew R. Bentley、Olga V. Ilyichova、Geqing Wang、Martin L. Williams、Gaurav Sharma、Wesam S. Alwan、Rebecca L. Whitehouse、Biswaranjan Mohanty、Peter J. Scammells、Begoña Heras、Jennifer L. Martin、Makrina Totsika、Ben Capuano、Bradley C. Doak、Martin J. Scanlon

  DOI：10.1021/acs.jmedchem.0c00111

  日期：2020.7.9

  A bottleneck in fragment-based lead development is the lack of systematic approaches to elaborate the initial fragment hits, which usually bind with low affinity to their target. Herein, we describe an analysis using X-ray crystallography of a diverse library of compounds prepared using microscale parallel synthesis. This approach yielded an 8-fold increase in affinity and detailed structural information for the resulting complex, providing an efficient and broadly applicable approach to early fragment development.