N-ethyl-2-((4-(ethylamino)-6-(5-(3-(trifluoromethyl)benzoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1,3,5-triazin-2-yl)amino)-2,3-dihydro-1H-indene-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-ethyl-2-((4-(ethylamino)-6-(5-(3-(trifluoromethyl)benzoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1,3,5-triazin-2-yl)amino)-2,3-dihydro-1H-indene-2-carboxamide
• 化学式: C₃₀H₃₃F₃N₈O₂
• 分子量: 594.64
• InChiKey: WGGWZULYFUEHAJ-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  43.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  115.38
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  2-((4-chloro-6-(5-(3-(trifluoromethyl)benzoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1,3,5-triazin-2-yl)amino)-N-ethyl-2,3-dihydro-1H-indene-2-carboxamide 、 乙胺盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以63%的产率得到N-ethyl-2-((4-(ethylamino)-6-(5-(3-(trifluoromethyl)benzoyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)-1,3,5-triazin-2-yl)amino)-2,3-dihydro-1H-indene-2-carboxamide
  参考文献：
  名称：

  Application of encoded library technology (ELT) to a protein–protein interaction target: Discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists

  摘要：

  The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.050

文献信息

• Application of encoded library technology (ELT) to a protein–protein interaction target: Discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists
  作者：Christopher S. Kollmann、Xiaopeng Bai、Ching-Hsuan Tsai、Hongfang Yang、Kenneth E. Lind、Steven R. Skinner、Zhengrong Zhu、David I. Israel、John W. Cuozzo、Barry A. Morgan、Koichi Yuki、Can Xie、Timothy A. Springer、Motomu Shimaoka、Ghotas Evindar

  DOI：10.1016/j.bmc.2014.01.050

  日期：2014.4

  The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. (c) 2014 Elsevier Ltd. All rights reserved.