3-((2S,4R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(4-(2,2,2-trifl uoro-1-hydroxy-1-phenylethyl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamido)propanoic acid | 1393724-26-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 3-((2S,4R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(4-(2,2,2-trifl uoro-1-hydroxy-1-phenylethyl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamido)propanoic acid
• CAS: 1393724-26-9
• 化学式: C₃₃H₃₀F₃N₅O₆
• 分子量: 649.626
• InChiKey: JFBQXTIDIUTBIV-RHAUSLOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  47.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  146.88
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  (2S,4R)-H-L-Pro(4-N3)-OH 在 3,3,3-膦三基三丙酸 、 碳酸氢钠 、 copper(II) sulfate 、 N,N-二异丙基乙胺 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 3-((2S,4R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(4-(2,2,2-trifl uoro-1-hydroxy-1-phenylethyl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamido)propanoic acid
  参考文献：
  名称：

  Discovery of Small-Molecule Interleukin-2 Inhibitors from a DNA-Encoded Chemical Library

  摘要：

  AbstractLibraries of chemical compounds individually coupled to encoding DNA tags (DNA‐encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high‐quality DNA‐encoded chemical library comprising 30 000 drug‐like compounds; this was screened in 170 different affinity capture experiments. High‐throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor‐associated antigen carbonic anhydrase IX (CA IX) and the pro‐inflammatory cytokine interleukin‐2 (IL‐2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL‐2 was confirmed by molecular docking. Our findings suggest that DNA‐encoded chemical libraries allow the facile identification of drug‐like ligands principally to any protein of choice, including molecules capable of disrupting high‐affinity protein–protein interactions.

  DOI：

  10.1002/chem.201200952